DNA, the Keeper of Life's Secrets, Starts to Talk

DNA, penjaga rahasia kehidupan, mulai dibicarakan

Fifty years ago, on Saturday, Feb. 28, 1953, two young scientists walked into the Eagle, a
dingy pub in Cambridge, England, and announced to the lunchtime crowd that they had
discovered the secret of life.
By divining the chemical structure of DNA, the archive of life, James D. Watson and
Francis Crick had seen how the molecule could encode information in the copious quantities
necessary to program a living cell.
Years later Dr. Crick's wife, Odile, told him she had not believed him, he has written. "You
were always coming home and saying things like that, so naturally I thought nothing of it," she
said.
But on that occasion the claim was true, and it set in motion a revolution that has continued
to unfold to this day, much of it guided by the two original discoverers.
Research is a slow process, often with years between each eureka, and even today the DNA
revolution remains largely behind laboratory doors, in the form of biologists' ever intensifying
understanding of the mechanisms of life. But a few powerful inventions — forensic DNA, a new
wave of DNA-based drugs — have already had considerable effect, and many researchers
believe they are just a foretaste.
They expect new medical treatments and diagnostic tests, based on a thorough
understanding of DNA, for cancer, heart disease and other long intractable maladies. Yet like
any powerful technology, DNA will doubtless bring vexing choices: whether to modify the
human genome with inheritable genes that will eliminate disease and enhance desired qualities,
for one.
And there are outright dangers, like the possibility that DNA techniques will be used to
make novel biological weapons.
The 50th anniversary of the discovery of DNA's double helix may be more than just a round
number. It comes while both its founders are still alive and active: Dr. Crick published an article
on the nature of consciousness just this month.
The human genome, obtained in a very rough draft in 2001, is becoming more polished.
New technologies have been invented for interpreting the genome's enigmatic archive. Biological
laboratories are engaged in a thousandfold scale-up, from studying one gene at a time to
examining whole genomes. And DNA, after a long gestation, is in the throes of passing from a
pure science to an applied one.
After figuring out the structure of DNA, Dr. Crick and Dr. Watson realized that the sequence
of units in the DNA must carry the code in some way for the structure of the proteins that are the
working parts of a cell. But they did not foresee that the entire genomes would one day be
decoded.
 "Did we appreciate how important DNA was? Yes we did," Dr. Crick said in an interview
this month from his home in Southern California. "We did see the shape of the genetic code. But
we didn't foresee rapid sequencing."
Although the text of the genomic message is an eye-glazing march of A's, G's, C's and T's
that then require years of interpretation, the genome era has already raised biology to a new scale
of operations and amplified the tools at biologists' disposal.
"The pace of discovery is going unbelievably fast," Dr. Watson said in an interview last
month at his Cold Spring Harbor Laboratory on Long Island.
The Watson-Crick discovery showed that DNA records genetic information in the form of a
four-letter alphabet. But obtaining the text of the message that evolution has taken some four
billion years to compile was no easy task. It was another 20 years, in the mid-1970's, before one
of their Cambridge colleagues, Dr. Fred Sanger, worked out an ingenious method for
determining the order of the letters in a stretch of DNA.
But Dr. Sanger's method was manual and could decode long DNA messages only with great
difficulty. Others, chiefly scientists at Applied Biosystems, had to automate the method and
design DNA sequencing machines that could handle genome-size lengths of DNA. Another
essential advance was the PCR technique, invented by Dr. Kary Mullis, for amplifying defined
stretches of DNA into workable quantities.
The genome era began on May 25, 1995, when Dr. J. Craig Venter announced that he had
decoded the first genome of a single-celled organism, a bacterium known as Haemophilus
influenzae. Since then about a hundred bacterial, plant and animal genomes have been decoded,
including the C. elegans roundworm, the Drosophila fruit fly and the mouse — laboratory
organisms of vital interest to biologists.
With whole genomes available for study, biologists can at last begin to see the precise
mechanics of natural selection, the process that Darwin intuited without any knowledge of its
physical basis.
As each new genome is deciphered, the tree of life comes into clearer focus. Even creatures
as far apart as man and mouse have turned out to possess amazingly similar sets of genes, each
with a similar sequence of DNA units. So far each new genome has turned out to have some
novel genes special to its own species, as well as a core set having to do with the cell's basic
operations, which seem very ancient and probably trace back close to the origin of life.
This genomic data — three billion units apiece for animals like mice and humans — has
presented biologists with a whole new set of challenges. New devices, called microarrays or
expression chips, have been invented for examining the activity of thousands of genes at a time.
A set of special chemicals, known as an RNAi library, was announced last month for inactivating
each of the genes in the laboratory roundworm.
A thriving new branch of science, often called computational or "in silico" biology, has
emerged to analyze the genes and other component parts of a genome and to compare one
genome to another. These techniques, developed for handling many genes at a time, give
biologists hope that they can understand the whole human genome, now thought to contain some
30,000 or so genes.
"A constellation of things is going on that make this a special time in biology," said Dr.
Thomas Cech, president of the Howard Hughes Medical Institute, which finances major
biomedical research. "Many of us underestimated how powerful a tool the genome would be. To
be able to ask a question of 30,000 genes at the same time and let the system tell you the answer
is incredibly exciting. You can unveil a process in a single-celled organism and then use
computers to discover by in silico experiments the human counterpart. That in itself has largely
transformed the way a lot of biology is done."
The ability, gift of the genome sequence, to track thousands of genes at the same time puts
biologists in the position of being able to analyze the living cell in action as it does its
housekeeping or responds to the ceaseless chatter of signals from its neighbors.
The genomic era is also bringing about a quantum leap in biologists' capabilities, drawing
almost within contemplation one of biology's ultimate goals, that of understanding a whole
organism in terms of its DNA.
For now, the DNA revolution is largely confined to understanding nature, not changing it.
Yet the few applications that have already appeared leave little doubt of the technology's
potential.
DNA as a means of individual identification, first invented by Sir Alec Jeffreys of the
University of Leicester in England in 1984, has developed into a hallmark forensic technique,
strong enough to overturn verdicts based on shakier forms of evidence like eyewitness testimony.
Applied to stored biological evidence, DNA fingerprinting has proven the innocence of
many convicted inmates. To date the Innocence Project at the Benjamin N. Cardozo School of
Law, run by Barry C. Scheck and Peter J. Neufeld, has exonerated 124 people. In Illinois, DNA
evidence cleared so many death row inmates that Gov. George Ryan lost confidence in his state's
justice system. Just before leaving office last month, he commuted all death sentences to prison
terms of life or less.
DNA testing has jolted the justice system because, properly used, it is an almost infallible
identifier of biological tissue. In Britain, which collects DNA from everyone convicted of a
crime, a growing database has allowed the police to score many "cold hits," the match of DNA
from tissue at a crime scene to someone not on any list of suspects. The impressive reach of
DNA fingerprinting, both to snare the guilty and clear the innocent, has prompted suggestions for
larger DNA databases, as well as counterarguments from civil libertarians.
DNA is also an unrivaled genealogical archive. By examining the DNA of the living,
biologists can reach back and resolve many otherwise inaccessible questions. DNA evidence has
added weight to the oral tradition, dismissed by almost all historians, that Thomas Jefferson had
a second, unacknowledged family with his slave Sally Hemings. From the DNA of people living
today, geneticists can infer the size of the ancestral human population and track its movements
across the globe as the first modern humans dispersed from Africa.
 DNA has already been used to modify crops, building bacterial genes for countering insects
into corn and cotton, and adding genes from daffodils and bacteria to help rice make vitamin A.
But the artificial mingling of genes from different species makes some people uncomfortable,
and genetically modified crops have encountered resistance, especially in Europe.
A new wave of DNA-based drugs is slowly reaching the market, beginning with genetically
engineered forms of insulin and growth hormone and now including highly ingenious
substances, based on a deep genetic knowledge, like Enbrel, for rheumatoid arthritis, and
Gleevec, a startlingly effective treatment for chronic myelogenous leukemia.
Waiting in the wings is a new wave of DNA-based diagnostic tests. One is a test for an
errant gene that is mutated early in many cases of colon cancer. Developed by Dr. Bert
Vogelstein of Johns Hopkins University, the test is applied to a stool sample and, together with
other genetic tests, could provide a cheaper and more acceptable screen for colon cancer than
colonoscopy.
The 30,000 or so genes in the human genome can now be programmed into microarrays and
used to profile the characteristic pattern of gene activity in a cancerous cell.
Dr. Todd Golub of the Whitehead Institute Center for Genome Research has pioneered the
use of gene expression chips to distinguish, within a given kind of cancer, previously
unrecognized subtypes that respond differently to treatment. He hopes the chips will pinpoint
both the errant genes special to particular types of cancer as well as gene changes common to all
cancer cells.
"We are looking for magic bullets that target particular types of cancer but also for the
Achilles' heel that unites many different types of cancer," Dr. Golub said. The tests, though yet to
be approved by the Food and Drug Administration, show the likely power and scale of genomic
era medicine.
A principal goal of the Human Genome Project was to identify the errant genes that underlie
common diseases, like diabetes, cancer, obesity, schizophrenia and Alzheimer's. These disease
genes have proved highly elusive, perhaps because it takes several errant genes in combination to
cause the disease, and the contribution from each is hard to detect.
A remarkable experiment is now under way in Iceland, where a company called Decode
Genetics has constructed a genealogy of much of the population. With it, Decode can build large
pedigrees for patients with each disease of interest. The company then scans the genomes of
related patients, looking for segments of chromosome they may have inherited from a common
ancestor. Within these shared segments it looks for variant genes that may contribute to the
disease.
The company has identified several disease-causing genes, including one for schizophrenia,
and has inferred the general location of several others.
From disease gene to drug is a long path, but identifying an errant gene gives a deep, often
novel, insight into the cause of disease and supplies new targets for drug makers.
 Implicit in the understanding of DNA is the possibility of changing it, a prerogative until
now reserved for evolution. Gene therapy, the idea of patching up tissues by delivering the
corrective form of an errant gene, has so far been a failure. Even when it works, its changes will
not outlast the patient.
But another approach, not yet technically possible or acceptable, is to change the human
genome in a heritable way. Instead of devising costly drugs or therapies to treat the same
diseases in each generation, why not go straight to the source and fix all known errant genes in
the egg or sperm? Germ line genetic engineering, as it is called, would make permanent fixes to
be passed from one generation to another. Advocates argue that however expensive it might be to
produce each perfect baby, the cost would be a fraction of the lifetime health care otherwise
needed.
Such proposals arouse serious ethical concerns, from religious objections to interventions
that seem to usurp a creator's role, to biologists' fears that genetic manipulation will subvert the
essence of human nature.
The DNA revolution is likely to present many such quandaries. It will increasingly provide
the means to repair and improve the machinery of life. But human ideas for redesign, which
might include items like perfect health and greater longevity, have little in common with
evolution's procedure of natural selection, which thrives on mutation and mortality.
Like all technology, DNA may have military uses. Though it is hard to improve on the
deadliness of natural scourges, that does not mean it will always be impossible. "If we manage
not to exploit biology for hostile purposes it will be the first time our species has ever refrained
from such exploitation," says Dr. Matthew Meselson, a founder of molecular biology who has
long worried about biological warfare. "And if we don't refrain, I don't know how to predict what
course it would take. There is only one human species."
Biologists recognize the depth of public concerns about genetic engineering. Yet most hope
that public can be educated to make what they regard as the right choices. Dr. Watson was
among the group of scientists who warned in 1974 of the possible dangers of recombinant DNA,
the technique that first allowed genes to be moved from one species to another. At the Asilomar
conference the next year scientists imposed voluntary restrictions on experiments while the
possible hazards were assessed.
Though Dr. Watson soon decided those dangers were overblown, he still believes that
scientists should talk frankly about the possibilities, good and bad, of their work.
"It is far better to tell it as it is and take the risk," he said. "We should expect a constant
concern from society as to where our knowledge is leading and whether to deploy it. That
certainly existed in the past, for instance in the opposition to automobiles. But once you put
someone in an auto you won't get them on a horse."
Dr. Watson has recently become an advocate for being open to the idea of germ line genetic
engineering. "Some think there is something wrong about enhancing people," he said. Dr. Crick,
who has worked for the last 25 years on the problem of consciousness, says he does not expect it
will yield to any sudden breakthrough. "At the origin of life things had to be simple," he said.
"But when you come to consciousness it's probably a very late development in evolution."
 Both at the beginning of life and at its culmination, DNA has more to tell.
Dalam Bahasa Indonesia
Tahun limapuluh yang lalu, pada hari sabtu, feb. 28,1953, dua ilmuwan muda memasuki
elang, tempat untuk minum-minum lusuh di cambridge, inggris, dan mengumumkan kepada
orang banyak waktu istirahat makan siang mereka telah menemukan itu rahasia hidup.
Dengan meramalkan struktur kimia dna, arsip hidup, yakobus d. watson dan franci
kekejangan pada urat leher telah melihat bagaimana molekul dapat menyandikan informasi di
jumlah banyak tulisannya perlu ke program sel hidup.
bertahun-tahun kemudian dr. crick' istri, odile, memberitahu dia dia tidak [pernah] percaya
dia, dia telah menulis. " kamu selalu rumah datang dan mengatakan hal-hal seperti itu, secara
alami saya berpikir tidak ada tentangnya, " dia mengatakan.
tetapi pada itu kesempatan menuntut benar, dan ini menggerakkan menjalankan revolusi
yang telah melanjutkan mengungkapkan sampai hari ini, banyak tentangnya menuntun oleh yang
dua asli discoverer.
riset lambat proses, sering dengan tahun diantara setiap eureka, dan bahkan hari ini dna sisa
revolusi sebagian besar di belakang pintu laboratorium, dalam wujud ahli ilmu biologi' pernah
memperhebat kesepakatan mekanisme hidup. tetapi beberapa penemuan bertenaga - forensik
dna, gelombang baru dna-based narkoba - punya telah mempunyai efek dapat
mempertimbangkan, dan banyak peneliti percaya mereka sekedar rasa pendahuluan.
mereka mengharapkan pengurusan medis baru dan percobaan diagnostik, berdasarkan
kesepakatan cermat dna, untuk kanker, penyakit jantung dan keras kepala panjang lain maladie.
seperti umumnya masih teknologi bertenaga, dna akan yakin membawa mendongkolkan aneka
pilihan: apakah memodifikasi manusia genome dengan inheritable gen yang akan
menghancurkan penyakit dan memperbesar menginginkan kualitas, untuk satu.
dan di sana bahaya pasti, suka itu kemungkinan dna teknik akan digunakan membuat novel
senjata-senjata biologis.
50th tahunan penemuan dna' pilihan ganda mungkin lebih dari sekedar angka bulat. ini
datang sementara keduanya pendiri nya masih hidup dan giat: dr. kekejangan pada urat leher
menerbitkan artikel di kesadaran sifat alami hanya bulan ini.
manusia genome, memperoleh di sangat rancangan di 2001, sedang menjadi banyak
memoles. teknologi baru telah menciptakan untuk menginterpretasikan genome' arsip merupakan
teka-teki. laboran biologis terlibat dalam thousandfold scale-up, dari belajar satu gen pada waktu
yang sama ke keseluruhan penganalisaan genome. dan dna, setelah kehamilan panjang, di
kelabakan melewati dari ilmu pengetahuan murni ke menerapkan satu.
setelah figuring keluar struktur dna, dr. kekejangan pada urat leher dan dr. watson
mewujudkan bahwa rangkaian satuan di dna harus membawa kode dalam beberapa jalan untuk
struktur protein itu bekerja bagian-bagian dari sel. tetapi mereka tidak meramalkan bahwa
seluruh genome akan satu ketika memecahkan kode.
" apakah kami menghargai bagaimana penting dna? ya kami, " dr. kekejangan pada urat
leher mengatakan di wawancara bulan ini dari rumah dia di selatan california. " kami lihat
bentuk kode genetis. tetapi kami tidak meramalkan peruntunan cepat. "
meskipun teks genomic pesan eye-glazing maret dari a', g', c' dan t' itu kemudian
memerlukan tahun tafsiran, genome era punya telah mengangkat biologi ke skala baru operasi
dan memperkuat alat-alat dapat mempergunakan ahli ilmu biologi'.
 " langkah penemuan bukan main cepat, " dr. watson mengatakan di wawancara bulan yang
lalu dingin dia melompat laboratorium bandar di pulau panjang.
watson-crick penemuan menunjukkan itu dna catatan informasi genetis dalam wujud four-
letter abjad. tetapi memperoleh teks pesan evolusi itu telah mengambil empat milyar tahun
mengumpulkan tidak tugas mudah. ini lainnya 20 tahun, di mid-1970', sebelum salah satu dari
mereka cambridge kolega, dr. fred sanger, memecahkan metode pandai untuk menentukan
pesanan surat-surat di bagian dna.
tetapi dr. sanger' metode penuntun dan dapat kodekan panjang dna pesan-pesan hanya
dengan sulit besar. lain, terutama ilmuwan menerapkan biosystem, mempunyai mengotomatiskan
metode dan desain dna mesin peruntunan yang dapat menangani genome-size panjang dna.
lainnya kemajuan pokok pcr teknik, direka oleh dr. kary mulli, untuk memperkuat didefinisikan
membentang dari dna ke jumlah dapat dikerjakan.
genome era mulai mengerjakan mungkin 25,1995, bila dr. j. craig venter mengumumkan
bahwa dia telah memecahkan kode pertama genome dari single-celled organisme, bakteri
mengetahui sebagai haemophilu influenzae. sejak itu tentang hasil bakteri seratus, tanaman dan
hewan genome telah memecahkan kode, termasuk c. elegan cacing gelang, drosophila buah
terbang dan tikus - organisme laboratorium minat sangat penting ke ahli ilmu biologi.
dengan keseluruhan genome tersedia untuk belajar, ahli ilmu biologi dapat akhirnya mulai
lihat mekanika akurat pilihan alami, proses itu darwin intuited tanpa pengetahuan dasar fisik.
sebagai setiap baru genome membaca dengan susah payah, pohon hidup datang ke fokus
lebih jelas. bahkan makhluk sebagai jauh terpisah sebagai pria dan tikus telah memutar ke luar
untuk memiliki dengan mengagumkan mirip satuan gen, setiap dengan mirip rangkaian dna
satuan. sejauh ini setiap baru genome telah memutar ke luar untuk punya khusus gen novel ke
spesies sendiri, sebaik seperangkat sangat setia setelah mempergunakan cell' operasi dasar, yang
bampak sangat kuno dan mungkin menelusur balik dekat dengan asal hidup.
ini genomic data - tiga milyar satuan masing-masing untuk hewan suka tikus dan manusia -
telah menyajikan ahli ilmu biologi dengan keseluruhan baru satuan tantangan. alat baru,
memanggil microarray atau ekspresi memotong, telah menciptakan untuk penganalisaan kegiatan
beribu-ribu gen pada waktu yang sama. kimia khusus satu set, mengenal sebagai rnai
perpustakaan, diumumkan bulan yang lalu untuk inactivating setiap gen di cacing gelang
laboratorium.
cabang baru subur ilmu pengetahuan, sering memanggil computational atau " di silico"
biologi, telah muncul menganalisis gen dan bagian-bagian dari menjadikan lengkap lain genome
dan ke perbandingan satu genome ke lainnya. teknik ini, membangun untuk menangani banyak
gen pada waktu yang sama, beri ahli ilmu biologi harap bahwa mereka dapat mengerti manusia
keseluruhan genome, sekarang berpikir berisi 30,000 atau gen.
" rasi bintang berlangsung itu membuat ini khusus waktu di biologi, " mengatakan dr. thoma
cech, presiden howard hughe institut medis, yang anggarkan utama biomedical riset. " banyak
dari kita meremehkan bagaimana bertenaga alat genome akan. untuk;menjadi dapat minta
pertanyaan 30,000 gen pada waktu yang sama dan biarkan sistem memberitahu kamu menjawab
dengan tidak dipercaya rangsang. kamu dapat unveil proses di single-celled organisme dan
kemudian gunakan komputer menemukan oleh di silico percobaan pasangan manusia. itu dengan
sendirinya punya sebagian besar menjelma jalan biologi banyak berbuat. "
kemampuan, hadiah genome rangkaian, ke jejak beribu-ribu gen pada waktu yang sama
meletakkan ahli ilmu biologi di posisi dapat menganalisis yang hidup sel dalam perang sebagai
ini kerumah-tanggaan nya atau bereaksi terhadap terus menerus mengoceh sinyal dari tetangga
nya.
genomic era juga membawa tentang kuantum meloncat di kemampuan ahli ilmu biologi',
menggambar hampir dalam perenungan salah satu dari biology' tujuan terakhir, itu kesepakatan
organisme keseluruhan nya dalam kaitan dengan dna.
untuk sekarang, dna revolusi sebagian besar terbatas pada alami kesepakatan, tidak merubah
ini. minoritas masih aplikasi yang punya telah muncul tinggalkan meragukan kecil technology'
potensial.
dna sebagai alat pengenalan sendiri, pertama menciptakan oleh pak alec jeffrey universitas
leicester di inggris di 1984, telah membangun ke membubuhkan cap teknik forensik, cukup kuat
menjatuhkan keputusan hakim berdasarkan di shakier bentuk bukti suka kesaksian saksi mata.
berlaku untuk tersedia bukti biologis, dna fingerprinting telah membuktikan kepolosan
menghukum narapidana. sampai saat ini proyek kepolosan di benjamin n. cardozo [rombon
hukum, melew barry c. scheck dan petrus j. neufeld, telah membebaskan dari tuduhan 124 orang.
di illinoi, dna bukti bersih sangat banyak narapidana baris kematian itu gov. george ryan
keyakinan hilang di dia state' sistem keadilan. tepat sebelum meninggalkan kantor bulan yang
lalu, dia pulang pergi semua kalimat kematian ke syarat-syarat penjara hidup atau kurang.
dna ujian telah menggoyangkan sistem keadilan karena, semestinya menggunakan, ini
manjur hampir identifier dari tisu biologis. di inggris, yang mengumpulkan dna dari semuanya
menghukum dari kejahatan, tumbuh basis data telah mengizinkan polisi ke nilai banyak" dingin
mengenai, " korek api dna dari tisu pemandangan kejahatan ke seseorang tidak di beberapa daftar
mencurigai. mengesankan mencapai dari dna fingerprinting, keduanya ke perangkap yang
bersalah dan cerah tidak bersalah, telah membisikkan saran untuk lebih besar dna basis data,
sebaik counterargument dari sipil libertarian.
dna juga arsip berkenaan dengan silsilah tak ada taranya. dengan penganalisaan dna yang
hidup, ahli ilmu biologi dapat mencapai kembali dan memisahkan banyak jika tidak pertanyaan
tidak dapat dicapai. dna bukti telah menambahkan berat kepada tradisi dengan lidah, dipecat oleh
hampir semua ahli sejarah, itu thoma jefferson mempunyai kedua, tidak diakui keluarga dengan
dia bekerja keras penerobosan keluar kepungan musuh heming. dari dna orang hidup hari ini,
ahli genetika dapat mengambil keputusan ukuran populasi manusia nenek moyang dan jejak
pergerakan nya melintasi bola bumi sebagai pertama manusia modern bubar dari afrika.
dna punya telah menggunakan memodifikasi hasil, membangun gen hasil bakteri untuk
membalas serangga ke jagung dan kapas, dan menambahkan gen dari bunga kuning daun kecil
dan bakteri membantu nasi membuat vitamin. tetapi buatan bercampur gen dari berbeda spesies
membuat gelisah sebagian orang, dan genetically hasil dimodifikasi telah temu pertahanan,
khususnya di eropa.
gelombang baru dna-based narkoba lambat mencapai pasar, mulai dengan genetically
engineered bentuk insulin dan hormon pertumbuhan dan sekarang termasuk sangat zat pandai,
berdasarkan dalam pengetahuan genetis, suka enbrel, untuk rheumatoid radang sendi, dan
gleevec, startlingly pengurusan efektif untuk kronis myelogenou leukemia.
menunggu di dalam sayap gelombang baru dna-based percobaan diagnostik. satu percobaan
untuk gen pesuruh yang mutated awal dalam banyak kesempatan kanker tanda titik dua.
dikembangkan oleh dr. tempat berlabuh vogelstein dari john hopkin universitas, percobaan
diterapkan ke bangku tanpa sandaran sederhana dan, bersama dengan percobaan genetis lain,
dapat sediakan lebih murah dan banyak layar dapat diterima untuk kanker tanda titik dua
daripada colonoscopy.
 30,000 atau gen di manusia genome dapat sekarang memprogramkan ke microarray dan
biasa penampang pola sifat kegiatan gen di sel berkenaan dengan kanker.
dr. todd golub whitehead pusat institut untuk genome riset telah memelopori menggunakan
ekspresi gen memotong membedakan, dalam ditentukan macam kanker, sebelumnya tak
mengenali subtype itu tukas dengan cara yang berbeda ke pengurusan. dia meloncat memotong
akan menunjukkan dengan tepat keduanya khusus gen pesuruh ke tipe teliti kanker sebaik gen
perubahan biasa ke semua sel kanker.
" kami cari peluru kegaiban sasaran itu tipe teliti kanker tetapi juga untuk achille tumit yang
mempersatukan banyak kanker jenis yang berbeda, " dr. golub mengatakan. percobaan,
walaupun masih untuk;menjadi menyetujui oleh makanan dan tata usaha narkoba, tunjukkan
mungkin kekuatan dan skala genomic obat era.
sasaran pokok manusia genome proyek mengenali gen pesuruh yang mendasari penyakit
biasa, suka kencing manis, kanker, kegemukan, penyakit jiwa dan alzheimer'. gen penyakit ini
telah terbukti sangat sukar dipahami, barangkali karena ini mengambil beberapa gen pesuruh di
kombinasi ke sebab penyakit, dan sumbangan dari setiap keras mengetahui.
eksprimen baik sekali sekarang dalam perjalanan di islandia, dimana perusahaan memanggil
membaca sandi genetika telah membangun asal-usul sebagian besar populasi. dengan itu,
kodekan dapat bangun asal-usul besar untuk sabar dengan setiap penyakit minat. perusahaan
kemudian membaca dengan cepat genome dari dihubungkan sabar, cari bagian kromosom
mereka mungkin telah menerima warisan dari leluhur biasa. dalam bagian dibagi ini ini melihat
untuk yang lain gen yang mungkin berperan untuk penyakit.
perusahaan telah mengenali beberapa menyease-causing gen, termasuk satu untuk penyakit
jiwa, dan telah inferred lokasi umum beberapa lain.
dari gen penyakit ke narkoba jalan sempit panjang, tetapi mengenali gen pesuruh
memberikan dalam, sering novel, kepandaian untuk memahami ke penyebab penyakit dan
menyediakan sasaran-sasaran baru untuk pembentuk narkoba.
tersembunyi dalam kesepakatan dna kemungkinan dari merubah ini, hak istimewa hingga
sekarang menyediakan untuk evolusi. terapi gen, gagasan untuk menambal atas tisu dengan
mengirimkan bentuk mengoreksi gen pesuruh, punya sejauh ini kegagalan. bahkan ketika ini
bekerja, nya perubahan akan tidak hidup lebih lama sabar.
tetapi lainnya mendekati, belum secara teknis mungkin atau dapat diterima, merubah
manusia genome di jalan turun temurun. daripada memikirkan narkoba mahal sekali atau
therapie mentraktir sama penyakit pada setiap generasi, mengapa tidak berjalan lurus kepada
sumber dan perbaiki semua mengetahui gen pesuruh di telur atau nutfah? garis benih teknik
genetis, karena (itu) adanya memanggil, akan membuat tetap menetapkan untuk;menjadi
melewati dari satu generasi ke lainnya. membela membantah bahwa bagaimanapun mahal ini
boleh memproduksi setiap bayi sempurna, berharga akan menjadi suatu bagian yang sangat kecil
pelayanan kesehatan seumur hidup jika tidak memerlukan.
demikian usul membangunkan etis serius mengenai, dari keberatan agama ke intervensi
yang bampak merampas creator' peranan, ke ahli ilmu biologi' manipulasi genetis itu takut akan
menumbangkan pokok alami manusia.
dna revolusi mungkin menyajikan banyak demikian quandarie. ini akan makin bertambah
menyediakan berarti memperbaiki dan majukan mesin hidup. tetapi ide manusia untuk redesign,
yang mungkin termasuk item suka sehat sempurna dan lebih besar umur panjang, hanya
mempunyai sedikit secara umum dengan evolution' prosedur pilihan alami, yang berhasil mutasi
dan kematian.
 seperti semua teknologi, dna mungkin punya militer menggunakan. walaupun ini keras
meningkatkan di deadlines dari cambuk alami, itu tidak maksud ini akan selalu tak mungkin. "
jika kita mengatur tidak mengeksploitasi biologi untuk maksud bermusuhan ini akan menjadi
pertama kali spesies kami telah pernah menahan diri dari demikian eksploitasi, " mengatakan dr.
matthew meselson, pendiri biologi molekuler yang punya panjang cemas akan peperangan
biologis. " dan jika kita tidak menahan diri dari, saya tidak tahu bagaimana cara meramalkan apa
kursus ini akan mengambil. ada hanya satu spesies manusia. "
ahli ilmu biologi mengakui kedalaman umum mengenai tentang teknik genetis. masih paling
harap umum itu dapat berpendidikan membuat apa mereka bertalian dengan sebagai benar aneka
pilihan. dr. watson di antara kelompok ilmuwan yang memperingatkan di 1974 mungkin bahaya
recombinant dna, teknik itu pertama gen mengizinkan untuk;menjadi memindahkan dari satu
spesies ke lainnya. di asilomar pembicaraan tahun depan ilmuwan menjatuhkan pembatasan
sukarela di percobaan sementara mungkin bahaya menaksir.
walaupun dr. watson segera memutuskan bahaya itu berlebihan, dia masih percaya ilmuwan
itu harus membicarakan sebetulnya tentang berbagai kemungkinan, baik dan jelek, dari mereka
bekerja.
" ini jauh lebih baik memberitahu ini karena (itu) adanya dan ambil resiko, " dia
mengatakan. " kami harus mengharapkan konstan mengenai dari masyarakat mengenai dimana
pengetahuan kami sedang memimpin dan apakah berbaris ini. itu tentunya hidup di masa lalu,
sebagai contoh di perlawanan ke mobil. tetapi sekali kamu meletakkan seseorang di otomatis
kamu won't memperoleh mereka di kuda. "
dr. watson punya baru-baru ini menjadi membela untuk terbuka bagi gagasan untuk garis
benih teknik genetis. " pikir ada sesuatu yang salah tentang tingkatkan orang, " dia mengatakan.
dr. kekejangan pada urat leher, siapa telah bekerja untuk lalu 25 tahun di permasalahan dalam
kesadaran, mengatakan dia tidak mengharapkan ini akan menyerah kepada beberapa mendadak
terobosan. " di asal barang hidup mempunyai untuk;menjadi sederhana, " dia mengatakan. "
tetapi bila kamu datang ke kesadaran ini adalah mungkin pengembangan sangat terlambat di
evolusi. "
keduanya pada awal hidup dan puncak nya, dna punya banyak memberitahu.

By NICHOLAS WADE Published: February 25, 2003

 Rekayasa Genetika / ADN Rekombian
1. Vektor, berupa plasmid bakteri atau viral ADN virus.

Gbr. Pembuatan plasmid dan mekanisme penyisipan gen

2. Bakteri, berperan dalam perbanyakan plasmid melalui perbanyakan bakteri.

Gbr. Pemisahan DNA oleh enzim restriksi

3. Enzim, terdiri dari enzim RESTRIKSI (pemotong plasmid/ADN) dan enzim LIGASE
(penyambung ptongan-potongan ADN)
Gbr. Proses produksi insulin manusia dengan rekayasa genetika
 THE CHEMICAL SIDE OF THE DOUBLE HELIX
The double helix has played a role in chemical research in the past 50 years, inspiring
chemists to solve biological problems

CELIA M. HENRY, C&EN WASHINGTON

The double helix. That two-word phrase is so firmly planted in our scientific lexicon that even a
good number of nonscientists recognize the reference to the structure of DNA. Many of us can't
remember a time when DNA wasn't recognized as being the genetic material or as taking the
form of two hydrogen-bonding complementary strands of base-pairing nucleotides wound
around a single axis.
MODEL
Although the B-form DNA structure that James D. Watson and Francis COMPOUND
H. C. Crick proposed in their April 25, 1953, letter to Nature made Watson (left) and Crick
only a limited splash at the time, the subsequent ripples revolutionized pose with their model
biology--particularly genetics--turning it into a molecular science. of DNA in 1953.
A. BARRINGTON
People pretty much agree about the impact that the double helix has BROWN/PHOTO
had on biology, but what about chemistry? How have chemists been RESEARCHERS INC.

inspired by this structure?

For one, Watson and Crick's model for DNA structure demonstrated that chemists could play a
role in solving biological problems.

Before the a-helix model suggested by Linus Pauling for proteins and the double-helix model for
DNA, the view of the structure of biological macromolecules was "blurry," says Albert
Eschenmoser, a chemistry professor at Scripps Research Institute and emeritus professor at the
Swiss Federal Institute of Technology, Zurich. "Pauling's -helix and Watson-Crick's double
helix were the first time that scientists could look at the structure of biopolymers as closely, as
sharply, as organic chemists had done at the time with the small molecules."
"Chemists often delve into biological problems once they know enough
chemical information to get their foot in the door." 

RECOGNITION A polyamide
dimer containing four pairs
of rings (Im/Py, Hp/Py, Py/Hp,
FOR CHEMISTS, the adage about a picture being worth a thousand and Py/Im, where Im =
imidazole, Py = pyrrole, and
words is true. "Many scientists, myself included, design and interpret Hp = hydroxypyrrole) can
their experiments based on pictures they carry around in their heads of read the minor groove of the
DNA double helix and
the molecules that are involved," says Thomas R. Cech, who received distinguish each of the
the Chemistry Nobel Prize in 1989 for his role in discovering the Watson-Crick pairs, G-C, T-A,
A-T, and C-G.
catalytic properties of RNA. Cech is president of the Howard Hughes COURTESY OF PETER
DERVAN
Medical Institute, and professor of chemistry and biochemistry at the
University of Colorado, Boulder.

"The better picture you have, the better experiment you can design to figure out how nature
works and the better you can interpret your results," Cech says.

"Watson and Crick provided the picture at just the right level of detail that allowed this whole
field to explode," he says. "Until a biological phenomenon is defined at the chemical level, it's
very hard for the chemist to get interested or involved. But the moment you have a specific
structure of sugar, phosphate, and heterocyclic base, all of a sudden you're in the world of
chemistry."

Eric T. Kool, a professor of chemistry at Stanford University, agrees. "Chemists often delve into
biological problems once they know enough chemical information to get their foot in the door.
That [DNA structure] was the foot in the door for chemists. I can speak for most organic
chemists. They love to look at pictures. This was the picture that really said this is a chemical
problem."

Interest in DNA chemistry predates Watson and Crick's structure. H. Gobind Khorana, emeritus
professor of chemistry and biology at Massachusetts Institute of Technology, was trained as an
organic chemist and was already working on ways to synthesize dinucleotides and
oligonucleotides in the early 1950s.

"I began to think about nucleotide synthesis and hooking two nucleotides together to make an
internucleotide bond as a starting point in dinucleotide and oligonucleotide synthesis," Khorana
recalls. "It was very clear at this time that one had to start this work to put nucleotides in a
specific sequence." He developed the first practical, but laborious, technique for synthesizing
nucleic acids, known as the phosphodiester method.

"All my time in the 1950s was spent making oligos, methods that we developed in Vancouver,
British Columbia, and later in Madison" at the University of Wisconsin, Khorana says. He
painstakingly combined his chemical techniques with enzymatic methods developed by Arthur
Kornberg to synthesize a 126-nucleotide transfer-RNA gene. Khorana shared the 1968 Nobel
Prize in Physiology or Medicine with Robert W. Holley and Marshall W. Nirenberg for their
contributions to deciphering the genetic code. Later, in the 1960s and early 1970s, Robert L.
Letsinger at Northwestern University, Marvin H. Caruthers at the University of Colorado, and
others developed methods of solid-phase synthesis of DNA that are still used in modern
automated DNA synthesizers.

"Chemical synthesis of DNA is the fundamental technology that has led the molecular biology
revolution," Cech says. DNA synthesis of probes and primers is a necessary first step for DNA
sequencing, genetic engineering, and the polymerase chain reaction. "All of a sudden, it was up
to the chemist to provide the essential tools to allow the field to fly forward," Cech says.
"Chemists provided not just little trinkets for the biologists, but actually the core technologies
that enabled molecular biology and biotechnology to go forward."

Peter B. Dervan, a chemistry professor at California Institute of Technology, believes that DNA
research can reveal new chemical principles. "We chemists are different from biologists and
physicists in that in addition to studying and trying to unravel principles of how the natural world
works, we are also inventors. In the process of trying to create new matter, new materials, we
come up against the limitations of our field. It helps define the next chemical question where our
understanding may need to be enriched," Dervan says. "In the exercise of trying to invent or
discover new materials that would mimic a biological system, we get to phrase new questions
and sometimes arrive at unanticipated discoveries that are inherently chemically interesting."

 
 "We chemists are different from biologists and physicists in that in
addition to studying and trying to unravel principles of how the natural
world works, we are also inventors."

DNA HAS INSPIRED Dervan to ask fundamental questions about molecular recognition. His
challenge was to invent a new polymer code that could read the edges of the Watson-Crick base
pairs in either the major or minor groove of the helix.

"Our first effort to create a language different from nature's proteins was to use a triple helix in
the major groove. We could not push beyond a two-letter code," Dervan says. His team was able
to recognize the purines--adenine (A) and guanine (G)--but couldn't recognize the pyrimidines
cytosine (C) and thymine (T). "It just showed the limitations of our understanding of molecular
recognition," Dervan says.

In parallel to the triple-helix work, Dervan also investigated the minor groove as a recognition
site. "The breakthrough was an unanticipated discovery. We discovered that an unsymmetrical
pair of imidazole and pyrrole stacked side by side would distinguish
GC from CG." Dervan's students invented a new ring pair of UNNATURAL PAIR Solution
structure (measured by high-
hydroxypyrrole and pyrrole that distinguishes TA from AT. resolution NMR) of the
nonpolar thymine analog
paired opposite adenine in a
Kool was drawn to DNA research in the 1980s by a talk given by DNA duplex. Such analogs
that don't form Watson-Crick
Dervan that "totally captivated" him. "I was fascinated by the hydrogen bonds have been
possibility that suddenly this is organic chemistry. It's not just biology, useful in the study of DNA
replication and repair.
but it is organic chemistry," Kool says. COURTESY OF ERIC KOOL

Kool is using DNA as a launching point to design new base pairs that
don't hydrogen bond but retain some of the properties of DNA. In natural DNA bases, the purine
adenine forms strong hydrogen bonds exclusively with the pyrimidine thymine. In a similar
fashion, the bases guanine and cytosine hydrogen bond with one another. Kool mimics the shape
but not the bonding ability of DNA bases by keeping the shape and size as close as possible to
those of the original base but removing the strongly polarized atoms and functional groups.
Kool's mimics are much less polar than natural DNA bases.

The DNA mimics have revealed when the Watson-Crick hydrogen bonds are important and
when they are not. "In the basic double helix--the two strands binding to one another in a specific
way--we still believe that Watson-Crick hydrogen bonds are pretty important," Kool says. "Our
molecules make it fairly clear that Watson-Crick hydrogen bonds are important for assembling
the helix and keeping it together."

Surprisingly, however, the hydrogen bonds turn out to be less important when enzymes
synthesize new DNA strands. "It's quite clear that a number of polymerase enzymes--the basic
replicators of nature--can copy DNA base pairs highly accurately and quite efficiently without
any Watson-Crick hydrogen bonding in a given base pair," Kool remarks. "You can't remove
them all forever, but you can remove some of them in an isolated way and it still works.
Although the hydrogen bonds are necessary to help hold the helix together, the enzymes that
copy DNA don't really care about them very much."

The mimics do not easily pair with opposite natural bases. "Despite the fact it looks like the
natural base, a mimic of adenine does not especially like to pair opposite thymine. When you
pair them in this way, it's strongly destabilizing to the DNA," Kool says. "If you replace the
partner of one of those modified bases with another modified base, it's not as destabilizing. We
have a couple of cases where those base pairs are as stable as a natural base pair."

Kool uses these new bases as structural probes. Because the bases don't change the overall shape
of the DNA, they can be used to understand the energetics and mechanisms of a variety of
interactions, such as enzyme recognition of DNA or nucleotides, protein bending or binding of
DNA, or water interaction with DNA. "We're studying various DNA polymerase enzymes and
various DNA repair enzymes using these molecules as probes of their mechanisms."

On the more applied side, Kool is using modified DNA to design diagnostic tools. For example,
he is designing molecules that fluoresce in the presence of specific genetic sequences. "We have
DNA [molecules] that can join themselves together to create a longer DNA. When this bond is
formed, it releases a fluorescence quencher and causes the molecules to light up with a specific
color. They can only join together when the correct genetic sequence is in the cell." He
anticipates that such assays could be used for genetically typing bacteria or cancer mutations.

INORGANIC CHEMISTS have also been drawn to DNA. For example, Stephen J. Lippard,
chemistry professor at MIT, first became interested in DNA in the 1960s, when he worked on
methods to sequence DNA using metal atoms and electron microscopy. "Let's say we wished to
identify the position of guanine nucleotide in DNA," Lippard explains. "The idea was to attach a
heavy atom label to every guanine and then spread the DNA out on an electron microscope grid
and use the electron microscope to read where the heavy atoms were. The process would be
repeated for the other nucleotides. The metal-DNA labeling chemistry was successful, but the
electron-beam energy applied to the microscope grids made the heavy atoms move so that the
picture was too fuzzy to ascertain the sequence.

However, the experience with metal-nucleic acid chemistry was valuable when Lippard turned
his attention to cisplatin, an anticancer platinum compound that targets DNA. His group has been
able to determine the structure of the intrastrand cross-linked adducts that form between DNA
and platinum.

"The current model that we are using to explain the anticancer activity is that the formation of
specific adducts blocks transcription on DNA," Lippard says. "When the RNA polymerase gets
stalled at the platinum cross-link, it triggers a variety of cellular responses that lead to the death
of the cancer cell."

Lippard's group is now working on "groove-crossing" compounds. "The platinum forms its
major adducts by binding to two guanines in the DNA major groove," he says. "The proteins that
bind to platinated DNA tend to recognize the widened shallow minor groove that occurs as a
consequence of the platinum adduct formation." Such protein binding inhibits repair of platinum
adducts and sensitizes cells to cisplatin. Lippard would like to design a single molecule that
could simultaneously form guanine cross-links in the major groove and fill the minor groove,
thus interfering with repair processes and still blocking transcription.

Lippard is now studying the repair of platinum adducts in larger, more complicated DNA
structures, such as nucleosomes, which consist of DNA wrapped around a histone core. "These
are very complicated molecules to synthesize," he says. "We can't use genetics to put platinum in
DNA. We have to make the DNA, platinating it in a specific place as part of the synthesis, and
then reconstitute it into higher order structures. By doing that, we believe we're getting closer to
understanding how the cell really processes DNA."

Jacqueline K. Barton, a chemistry professor at Caltech, was originally drawn to DNA because of
its structure. "When I was starting graduate school, I was very interested in beautiful structures.
DNA has an absolutely beautiful structure, and it has this interesting characteristic of being a
polymer as well, a polymer of p-stacked base pairs."

STACKING UP TAKING
The SHAPE
interactions of Double-helical
the base pairs elements in
cause these RNA can be
five DNA packed to
octamers with make tertiary
an structures.
intercalating COURTESY
metal complex OF SCOTT
to stack end- STROBEL
to-end in a
noncovalently
bonded
structure,
shown in this
crystal
structure.
COURTESY
OF
JACQUELINE
BARTON

BARTON IS AN EXAMPLE of a chemist who was inspired by DNA's structure to ask chemical
questions. "We started out asking a fundamental chemistry question: How are electrons or
electron holes transported through a DNA helix? Is this molecule particularly facile for electron
transfer and transport chemistry? To the first order, that question has nothing to do with
biology," Barton points out. "What we found is, in fact, because of the stacked base pairs, that
structure does indeed facilitate charge transport, and it's really sensitive to the structure. From
that point, we've come up with applications, such as developing new DNA-based diagnostics to
look at mutations and lesions in DNA. Now we're trying to understand the biological
consequences of that chemistry."

A large part of Barton's work involves developing molecules that can recognize various
sequence-dependent conformations of DNA. An early example of such work involved chiral
metal complexes in which right-handed metal complexes preferentially bound to the right-
handed DNA helix, taking advantage of DNA's simplest recognition element, the handedness of
its helix.

"Now we're interested in designing molecules that recognize specific sites. We're interested in
seeing if we can target mismatches, mistakes in DNA, in different kinds of ways," Barton says.
"We're taking advantage of the structural and thermodynamic distortions that are associated with
mismatches to see if we can design transition-metal complexes that allow us to target some sites
on DNA with specificity. It turns out that analogs of these complexes also carry out interesting
electron-transfer chemistry. We've exploited these metal complexes as probes of that charge-
transport chemistry on DNA."

With the metal complexes, Barton has found that DNA is capable of long-range charge transport.
"I could bind a metal complex to site A, use that metal complex to inject a hole into the DNA,
and oxidatively damage DNA at a distant site," she says. "We've been able to demonstrate this
oxidative damage at a distance as long as 200 Å."

A number of younger chemists and biochemists who cut their teeth on DNA are now studying
RNA.

"Once a chemist gets hold of a nucleic acid, whether it starts as RNA or DNA, it can end up
looking like something halfway in between," Cech says. "After all, the main difference between
the two is the 29-hydroxyl group, and as soon as chemists get their hands on DNA or RNA, they
tend to start mucking around with those 29-hydroxyl groups," he quips. "Those of us who live in
the RNA world consider DNA to be just a derivative of RNA anyway."

Scott A. Strobel, a professor in the departments of chemistry and molecular biophysics and
biochemistry at Yale, got his start as a graduate student in Dervan's lab working on triple-helix
DNA structures. "Part of the reason I moved from DNA to RNA is that RNA doesn't follow the
Watson-Crick rules," Strobel says. "In RNA, because one strand isn't used to template another,
you can actually have a molecule that folds back on itself. You end up with all kinds of things
that are exceptions to the Watson-Crick rules of base pairing and structure. We're interested in
what those pairings are and what kinds of structural and functional implications there are as a
result of having things that aren't simple duplexes."

Strobel uses a technique called nucleotide analog interference mapping (NAIM) to determine
what parts of RNA catalytic structures are important for their function. "We're considering a
nucleic acid to be a chemical. If it's a chemical, then it's one that we can modify," he says.

Of course, the simplest way to modify a nucleic acid is just to switch one base for another. "The
problem is that that's too sharp a sword on one side and too dull a sword on the other," he
laments. "If you mutate a G to a C, you've changed almost everything about the base, but you've
changed almost nothing about the backbone. It's still a ribose sugar; it's still a phosphate. No
matter what mutagenesis you do with a nucleic acid, the changes are too big on the base and too
little on the sugar."
Instead, Strobel makes more subtle changes to the nucleotides. So far, he has made about 70 or
75 different nucleotides that are variations of the original adenine, guanine, cytosine, or uracil.
The changes have included deleting 29- hydroxyl groups on the ribose, substituting fluorine for
the hydroxyl, and changing functional groups on the base. "We can modify or manipulate almost
every functional group on the base and most of them on the sugar. The caveat is that not only do
you have to be able to make them as a triphosphate, but they also have to be incorporated by an
RNA polymerase to be used in this assay."

 
"We are still just at the beginning in terms of understanding the driving
forces for RNA folding and tertiary-structure formation."

STROBEL HAS EXTENDED NAIM so that not only can he identify which functional groups are
important in a particular RNA molecule, but he can tell which nucleotides interact with one
another. "We knock out a functional group that we know is important, but we knock it out in
every molecule," he says. "If you repeat the original interference experiment in this background
where one of the functional groups that you knew was important was deleted, the outcome is that
its partner tends to no longer show interference. You can actually define tertiary interaction
partners. Within the group I intron, we've systematically found about a dozen of these that
effectively bring the active site very tightly woven together with multiple layers--not unlike an
onion--to create an active center."

Strobel considers nucleic acid interference suppression, as the second technique is called, to be
complementary to such structural techniques as X-ray crystallography and nuclear magnetic
resonance. "The beauty of it is that it's functional information that then has structural
implications."

Anna Marie Pyle, another professor in Yale's department of molecular biophysics and
biochemistry, is studying RNA structure. She started out working on small-molecule probes of
DNA structure in Barton's lab while Barton was at Columbia University; Pyle moved to Yale in
2002.

"I became very interested in the information content on the surface of the DNA major groove,
which got me interested in nucleic acid structure in general," Pyle says. "At the time, about 1990,
it became very clear through Tom Cech's work that RNA adopted a much more complex
structure than DNA. I decided to start studying RNA. It has a very interesting tertiary
architecture that is superimposed on its duplex structure."

At Yale, her research is focusing on the group of ribozymes--RNA molecules that catalyze
reactions--known as group II introns. "The discovery of ribozymes underscored the complexity
of RNA structure in a way that nothing else ever had," Pyle says. "To make an active site for
chemistry, something has to have a pretty interesting organization." She realized that ribozymes
were an optimal way to study nucleic acid structure because they report on their structure
through their activity.

"We work on the folding pathway of tertiary-structured RNA. We work on how it gets to the
folded state, and then we also work on the architectural arrangement of the folded molecule,"
Pyle says. "In the RNA field, we are just beginning to understand the alphabet of tertiary
interactions in RNA. We are trying to identify new types of interaction, to characterize their
thermodynamic signatures, and to understand how strong they are and what kind of context they
require for formation."
"Chemical synthesis of DNA is the fundamental technology that has led
the molecular biology revolution."

OF COURSE, biological applications of nucleic acids are important to chemists, but DNA has
also become more than just a biological molecule.

"The DNA molecule today can be viewed as a chemical reagent, quite apart from its role in
biology, although much of the work is inspired by what might be the positive consequences for
medicine or drug development or diagnosis of disease," Lippard says. "For even neglecting its
biological importance, there would still be a lot of interest in DNA as a fundamental molecule
for chemists to study and use as an object for chemical building blocks, sensing, polymer design,
etcetera, without any medical application whatsoever."

For example, Nadrian C. Seeman, a chemistry professor at New York University, is using DNA
as a building block to make nanometer-scale structures. "Although I DNA AS MATERIAL Seeman
have interests in biology, mostly I think about DNA as a chemical," he uses DNA to make structures
such as this cube.
says. "It has properties that can be exploited, particularly on the COURTESY OF NADRIAN
SEEMAN
nanometer scale." Seeman's interest originally sprang from a desire to
characterize Holliday junctions, four-armed DNA structures that are a
key step in genetic recombination.

"I didn't really feel that thinking about the DNA structure, except in a biological context, was a
really useful thing until I started up my own program somewhere around 1980," Seeman recalls.
"At that time, DNA was biology--period. Many of my early papers were rejected; occasionally, it
still happens when some referee says, 'Where's the biology?' The first thing we did that was of
any prominence [was to make] a DNA molecule that was connected like a cube. We sent it to a
prominent journal that will remain nameless. One referee said, 'This is spectacular,' and the other
referee said, 'Where's the biology?' People just could not get away from the idea that DNA had to
be associated with biology."

Seeman utilizes "sticky ends," single-stranded overhang at the ends of double-stranded DNA, to
direct the assembly of DNA objects. He needs to keep several things in mind when devising the
sequences that he uses.

"I come from a crystallographic background, so I think of things in terms of symmetry," he says.
"To a first approximation, we trash symmetry. We divide each strand into a series of overlapping
elements. A typical example is a 16-mer. We break it up into a series of 13 overlapping
tetramers. We insist that each of those be unique. We also insist that for any of the tetramers
going around the bend of the branch point, there be no complement to them, so they couldn't
form a double helix if they wanted to." Seeman has used these methods to make a variety of
structures, including cubes, truncated octahedrons, and two- and three-dimensional periodic
arrays.

Despite 50 years of research since Watson and Crick described the double helix, there are still
questions to be answered about higher order nucleic acid structures. "We are still just at the
beginning in terms of understanding the driving forces for RNA folding and tertiary-structure
formation," Pyle says. "We're still just at the beginning of defining the tertiary building blocks by
which an RNA folds, such that we can look at the sequence and know what it's going to do."

Kool has had three-dimensional models of DNA sitting on his desk since 1988. "At first I
wondered, how much can you look at this and continue to understand something new," he muses.
"I'm always amazed at needing to come back to the structure and look at some small nuance I
had forgotten. Yes, we're making modifications to it and making new synthetic molecules, but
we come back to this structure a lot."

Kool sees one of the great challenges as being whether people can design new genetic systems,
information-encoding systems that work in organisms or perhaps only in test tubes. "If we
understand enough about the structure and function of DNA, we ought to be able to design our
own," he notes.

Maybe we'll have the answers to those questions in time for the centennial of the double helix.
Struktur DNA
Hari Jumat tanggal 25 April tahun ini adalah hari ulang tahun ke-53 penemuan struktur
Deoxyribonucleic Acid (DNA). Pada tanggal 25 April 1953 lalu, dua ilmuwan muda asal Amerika dan
Inggris, James Watson dan Francis Crick mengumumkan proposal mereka mengenai struktur B-DNA
di jurnal ilmiah terkemuka Nature.

Karya ilmiah mereka yang berjudul "Molecular Strucure of Nucleic Acids: A Structure for
Deoxyribose Nucleic Acid" ini panjangnya hanya satu halaman (manuskripnya diketik adik Watson,
Betty), memakai hanya satu ilustrasi (digambar oleh istri Crick, Odile) dan enam daftar pustaka.
Sebuah artikel yang sederhana untuk suatu terobosan besar di bidang biologi dan kimia. Bahkan
ketika tulisan ilmiah ini terbit, surat kabar di Inggris tidak memberitakannya sampai tanggal 15 Mei,
ketika Sir Lawrence Bragg (direktur Laboratorium Cavendish dimana Watson dan Crick mengerjakan
riset mereka) memberikan kuliah di London yang lantas diliput oleh The News Chronicle of London.
Bukan itu saja. Walaupun Dr. Crick kemudian diwawancarai oleh BBC di musim gugur tahun itu,
penemuan struktur double helix (spiral ganda) DNA itu hanya diberitakan sekedarnya saja setelah itu.
Bahkan Dr.Robert C. Olby (sejarawan di University of Pittsburgh) mengatakan bahwa di majalah
Nature pada tahun yang sama, dari 20 artikel tentang DNA, hanya 7 yang menyebut double helix.

Kenapa berita tentang penemuan struktur DNA ini tidak begitu menggemparkan saat itu? Menurut
para sejarawan dan ahli Biologi, masih banyak pertanyaan yang belum dapat dijawab oleh teori
Watson-Crick saat mereka mengumumkan temuannya. Bagaimana struktur spiral ganda itu membuka
gulungannya? Bagaimana ia dapat memerintahkan sel untuk mereproduksi protein-protein? Apa kode
yang tersimpan didalamnya? Pertanyaan-pertanyaan ini baru terjawab dalam kurun waktu sepuluh
tahun kemudian, yang mencapai puncaknya dengan pemberian hadiah Nobel Kedokteran pada tahun
1962 kepada Dr. Watson, Dr. Crick dan Dr. Wilkins.

Jadi bagaimana cerita tentang penemuan struktur spiral ganda DNA ini?

Dr. Crick yang punya latar belakang pendidikan fisika dan berpengalaman kerja di British Admiralty
semasa perang akhirnya memilih karir sebagai periset ketimbang menggantikan posisi Dr. R.V. Jones,
kepala Inteligen Sains Inggris saat itu. Pada umur 35 tahun, dia kembali ke bangku kuliah untuk
meraih S3 di Universitas Cambridge dengan mempelajari struktur sinar X protein-protein.

Dr. Watson, yang punya ilmu tentang genetik bakteria dari AS, datang ke Cambridge juga untuk
mengambil PhD. Keduanya bertemu dan mulai berbincang-bincang mengenai struktur DNA, walaupun
pada saat itu, King's College di London yang lebih dikenal sebagai institusi yang mendalami masalah-
masalah DNA. Ada dua orang X-ray crystallographers yang bekerja meriset DNA di King's College-Dr.
Maurice Walkins dan Dr. Rosalind Franklin.
Untuk menghilangkan keraguan atas data-data sinar X yang diperoleh oleh X-ray crystallographers,
Crick dan Watson merasakan pentingya membuat model atas molekul yang sedang mereka pelajari.
Ketika Watson mendengar perincian dari hasil riset Dr. Franklin di sebuah seminar yang di bulan
November 1951, dia dan Crick percaya kalau mereka sudah punya data yang cukup untuk memulai
membuat model.

Model pertama mereka memiliki tiga rantai spiral, dengan grup-grup phosphate berada di dalam spiral
dan basa-basa (bases) menjulur keluar. Mereka lantas mengundang Dr. Walkins dan Dr. Franklin ke
Cambridge untuk melihat model tersebut. Tapi kedua periset tersebut malah mencemoohkan model
yang mereka buat. Rupanya Watson salah paham mengenai salah satu hasil ukuran Dr.Franklin.
Setelah kejadian ini, terjadi percakapan antara kedua direktur lab di King's College (Dr. John Randall)
dan di Cambridge (Dr. Lawrence Bragg). Mereka memutuskan supaya kedua ilmuwan muda itu
menghentikan kegiatan mereka membuat model-model DNA dan kembali ke riset resmi mereka yang
tidak berkenaan dengan DNA. Peralatan yang telah mereka pakai diberikan kembali ke King's College
dengan desakan supaya digunakan secepatnya sebelum Dr. Pauling memecahkan masalah struktur
DNA ini.

Sayangnya, Dr. Wilkins dan Dr. Franklin mengabaikan nasihat ini. Dan benar saja, pada bulan Januari
1952, Dr. Pauling mengumumkan bahwa dia telah menemukan struktur DNA. Tetapi struktur yang dia
ajukan memiliki tiga rantai dan Crick dan Watson tau ini bukan struktur yang benar. Akhirnya Watson
berhasil membujuk Dr. Bragg untuk mengizinkan mereka kembali membuat model sebelum Dr.
Pauling sadar dan membetulkan kesalahannya.

Crick telah mendeduksi dari data sinar X Dr. Franklin bahwa DNA pasti hanya memiliki dua rantai
spiral, paralel satu sama yang lainnya tetapi mempunyai arah yang berlawanan. Dia dan Watson
akhirnya sadar bahwa basa-basa DNA mestinya berada di dalam spiral, walaupun masih bingung
bagaimana komposisi acak basa-basa itu dapat membuat struktur yang rapi. Mereka pun memesan
guntingan-guntingan lempegan logam basa-basa tersebut untuk membuat model baru.

Watson yang tidak sabaran menunggu guntingan-guntingan logam itu, akhirnya memutuskan
membuat empat basa DNA (adenine, thymine, guanine dan cytosine, A, T, G, C) dari karton. Dia
mengutak-ngutik guntingan karton itu di atas meja belajarnya, mencoba memasang basa yang mirip
satu sama lainnya. Tapi tidak membuahkan hasil. Akhirnya dia melihat kalau pasangan A-T dan
pasangan G-C sama persis. Kedua pasangan ini yang dapat membuat anak tangga bentuk tangga
spiral struktur DNA. Masing-masing dari empat huruf itu dalam satu rantai pas berpasangan dengan
rantai satunya yang berlawanan arah. Dan jika rantai ini berpisah, masing-masing jadi template untuk
rantai urutan baru.

Maka terungkaplah struktur lengkap DNA setelah sekian lama terselebung misteri. Untuk pertama
kalinya manusia dapat melihat dan mengerti struktur pita molekul yang ditemukan di dalam
kromosom di dalam setiap sel di tubuh manusia ini.

Empat Nukleotida DNA:

P = Phosphate
D = Deoxyribose (Sugar)
A = Adenine (Purine)
G = Guanine (Purine)
C = Cytosine (Pyrimidine)
T = Thymine (Pyrimidine

Penemuan struktur DNA 50 tahun lalu ini telah memberikan banyak inspirasi untuk para kimiawan dan
tehnik kimiawan menyumbangkan ilmu mereka untuk membantu kemajuan di bidang Biologi dan
Kedokteran. Himpunan Kimiawan Amerika (American Chemical Society) bulan Maret lalu menerbitkan
artikel khusus di situs mereka membahas kontribusi dan riset para kimiawan dari berbagai sub-bidang
ilmu kimia dalam riset DNA ini. Ahli-ahli kimia di bidang kimia organik, kimia inorganik, biokimia
molekuler menceritakan riset-riset mereka yang berhubugan dengan DNA. Ada satu ahli yang percaya
bahwa riset DNA akan menemukan prinsip-prinsip kimia baru yang dapat digunakan untuk
menciptakan bahan-bahan jenis baru. Ada ahli lainnya yang menggunakan DNA sebagai bahan inti
untuk membuat struktur-struktur baru berskala nanometer, dan sebagainya. Masih banyak lagi topik-
topik riset lainnya yang berhubungan dengan DNA yang dapat dikerjakan oleh para kimiawan dan
tehnik kimiawan. Dan penemuan struktur molekul DNA inipun akhirnya menelurkan penemuan-
penemuan baru.
 Artikel Bioteknologi Rekayasa Genetika
By andtho

Bioteknologi adalah ilmu terapan biologi yang melibatkan disiplin ilmu mikrobiologi, biokimia,
genetika, dan biologi molekuler. Definisi bioteknologi secara klasik adalah teknologi yang
memanfaatkan agen hayati fan untuk menghasilkan barang dan jasa dalam skala industri untuk
memenuhi kebutuhan manusia. Sedangkan definisi secara modern adalah pemanfaatan agen
hayati yang telah direkayasa secara in vitro untuk menghasilkan barang dan jasa pada skala
industri.

Bioteknologi dikembangkan untuk meningkatkan nilai bahan mentah dengan memanfaatkan

kemamapuan mikroorganisme seperti bakteri dan kapang. Selain itu, bioteknologi juga
menggunakan sel tumbuhan atau hewan yang di biakkan sebagai bahan dasar berbagai proses
industri.

Adapun ciri utama bioteknologi, diantaranya:

1. Adanya aBen biologi berupa mikroorganisme, tumbuhan atau hewan
2. Adanya pendayagunsan secara teknologi dan industri
3. Produk yang dihasilkan adalah hasil ekstraksi dan pemurnian

REKAYASA GENETIKA

Rekayasa genetika dapat diartikan sebagai kegiatan manipulasi gen untuk mendapatkan produk
baru dengan cara membuat DNA rekombinan melalui penyisipan gen. DNA rekombinan adalah
DNA yang urutannya telah direkombinasikan agar memiliki sifat-sifat atau fungsi yang kita
inginkan sehingga organisme penerimanya mengekspresikan sifat atau melakukan fungsi yang
kita inginkan.

Sejarah rekayasa genetika dimulai sejak Mendel menemukan faktor yang diturunkan. Ketika
Oswald Avery (1944) menemukan fakta bahwa DNA membawa materi genetik, makin banyak
penelitian yang dilakukan terhadap DNA. Salah satu penelitian yang memberikan kontribusi
terbesar bagi rekayasa genetika adalah penelitian terhadap transfer (pemindahan) DNA bakteri
dari suatu sel ke sel yang lain melalui lingkaran DNA kecil yang disebut Plasmid.

Plasmid adalah gen yang melingkar yang terdapat dalam sel bakteri, tak terikat pada kromosom.
Melalui teknik plasmid dalam rekakayasa genetika tersebut, para ahli di bidang bioteknologi
dapat mengembangkan tanaman transgenik yang resisten terhadap hama dan penyakit.

Teknik hibridoma adalah penggabungan dua sel dari organisme yang sama ataupun dari sel
organisme yang berbeda sehingga menghasilkan sel tunggal berupa sel hibrid (hibridoma) yang
mamiliki kombinasi sifat dari kedua sel tersebut.

Para ahli berusaha melawan gen-gen perusak dalam inti sel itu dengan berbagai cara rekayasa
genetika. Upaya yang dirintis tersebut dikenal dengan istilah terapi genetik. Terapi genetik
adalah perbaikan kelainan genetik dengan memperbaiki gen. Sayangnya, penemuan itu tidak
segera dapat diterapkan. Dalam rekayasa genetika, ada kode etik yang melarang keras percobaan
ini pada manusia. Akan tetapi, para ahli tidak selamanya bersikap kaku sebab berbagai penyakit
fatal memang sulit disembuhkan kecuali dengan terapi genetik. Maka muncul pendapat tentang
perlu adanya dispensasi. Dispensasi itu dikeluarkan oleh Komite Rekayasa Genetika dari
Nasional Institute of Health (NIH) Amerika Serikat pada pertengahan tahun 1990.

Kloning , adalah proses menghasilkan individu baru yang identik satu sama lain karena
dihasilkan dari reproduksi aseksual. Pada tahun 1952, Robert Brigs dan Thomas J. King (AS)
mencoba teknik kloning pada katak. Sepuluh tahun kemudian (1962), John B. Gurdon juga
mencoba teknik kloning pada katak, namun percobaanya menghasilkan banyak katak yang
abnormal. Pada tahun 1986, Steen Willadsen (inggris) menkloning sapi dengan tujuan komersial
dengan metode transfer inti. Tahun 1996, Ian Willmut mengkloning domba. Ia menggunakan sel
kelenjar susu domba finn dorset sebagai donor inti dan sel telur domba blackface sebagai
resipien. Sel telur domba blackface dihilangkan intinya dengan cara mengisap nukleusnya keluar
dari sel menggunakan pipet mikro. Kemudian, sel kelenjar susu domba finn dorsetg difusikan
dengan sel telur blackface yang tanpa nukleus. Hasil fusi ini kemudian berkembang menjadi
embrio dalam tabung percobaan dan kemudian dipindahkan ke rahim domba blackface.
Kemudian embrio berkembang dan lahir dengan ciri-ciri sama dengan domba finn dorset, dan
domba hasil kloning ini diberinama Dolly. Dari 227 percobaan yang dilakukan oleh Wilmut,
hanya 29 yang berhasil menjadi embrio domba yang dapat ditransplantasikan ke rahim domba,
dan hanya satu yang berhasil dilahirkan menjadi domba normal.

Sumber : Buku Biologi SMA penerbit ERLANGGA

 A vision for the future of genomics research
Francis S. Collins1, Eric D. Green1, Alan E. Guttmacher1 & Mark S. Guyer1

Abstract

A blueprint for the genomic era.

The completion of a high-quality, comprehensive sequence of the human genome, in this fiftieth
anniversary year of the discovery of the double-helical structure of DNA, is a landmark event.
The genomic era is now a reality.

In contemplating a vision for the future of genomics research, it is appropriate to consider the
remarkable path that has brought us here. The rollfold (Figure 1) shows a timeline of landmark
accomplishments in genetics and genomics, beginning with Gregor Mendel's discovery of the
laws of heredity1 and their rediscovery in the early days of the twentieth century. Recognition of
DNA as the hereditary material2, determination of its structure3, elucidation of the genetic code4,
development of recombinant DNA technologies5, 6, and establishment of increasingly
automatable methods for DNA sequencing7, 8, 9, 10 set the stage for the Human Genome Project
(HGP) to begin in 1990 (see also http://www.nature.com/nature/DNA50). Thanks to the vision of
the original planners, and the creativity and determination of a legion of talented scientists who
decided to make this project their overarching focus, all of the initial objectives of the HGP have
now been achieved at least two years ahead of expectation, and a revolution in biological
research has begun.

Figure 1: Timeline

To view a larger version of this image download the pdf (1.9 M).

The project's new research strategies and experimental technologies have generated a steady
stream of ever-larger and more complex genomic data sets that have poured into public databases
and have transformed the study of virtually all life processes. The genomic approach of
technology development and large-scale generation of community resource data sets has
introduced an important new dimension into biological and biomedical research. Interwoven
advances in genetics, comparative genomics, high-throughput biochemistry and bioinformatics
are providing biologists with a markedly improved repertoire of research tools that will allow the
functioning of organisms in health and disease to be analysed and comprehended at an
unprecedented level of molecular detail. Genome sequences, the bounded sets of information that
guide biological development and function, lie at the heart of this revolution. In short, genomics
has become a central and cohesive discipline of biomedical research.
The practical consequences of the emergence of this new field are widely apparent. Identification
of the genes responsible for human mendelian diseases, once a herculean task requiring large
research teams, many years of hard work, and an uncertain outcome, can now be routinely
accomplished in a few weeks by a single graduate student with access to DNA samples and
associated phenotypes, an Internet connection to the public genome databases, a thermal cycler
and a DNA-sequencing machine. With the recent publication of a draft sequence of the mouse
genome11, identification of the mutations underlying a vast number of interesting mouse
phenotypes has similarly been greatly simplified. Comparison of the human and mouse
sequences shows that the proportion of the mammalian genome under evolutionary selection is
more than twice that previously assumed.

Our ability to explore genome function is increasing in specificity as each subsequent genome is
sequenced. Microarray technologies have catapulted many laboratories from studying the
expression of one or two genes in a month to studying the expression of tens of thousands of
genes in a single afternoon12. Clinical opportunities for gene-based pre-symptomatic prediction
of illness and adverse drug response are emerging at a rapid pace, and the therapeutic promise of
genomics has ushered in an exciting phase of expansion and exploration in the commercial
sector13. The investment of the HGP in studying the ethical, legal and social implications of these
scientific advances has created a talented cohort of scholars in ethics, law, social science, clinical
research, theology and public policy, and has already resulted in substantial increases in public
awareness and the introduction of significant (but still incomplete) protections against misuses
such as genetic discrimination (see http://www.genome.gov/PolicyEthics).

These accomplishments fulfil the expansive vision articulated in the 1988 report of the National
Research Council, Mapping and Sequencing the Human Genome14. The successful completion of
the HGP this year thus represents an opportunity to look forward and offer a blueprint for the
future of genomics research over the next several years.

The vision presented here addresses a different world from that reflected in earlier plans
published in 1990, 1993 and 1998 (refs 15–17). Those documents addressed the goals of the
1988 report, defining detailed paths towards the development of genome-analysis technologies,
the physical and genetic mapping of genomes, and the sequencing of model organism genomes
and, ultimately, the human genome. Now, with the effective completion of these goals, we offer
a broader and still more ambitious vision, appropriate for the true dawning of the genomic era.
The challenge is to capitalize on the immense potential of the HGP to improve human health and
well-being.

The articulation of a new vision is an opportunity to explore transformative new approaches to

achieve health benefits. Although genome-based analysis methods are rapidly permeating
biomedical research, the challenge of establishing robust paths from genomic information to
improved human health remains immense. Current efforts to meet this challenge are largely
organized around the study of specific diseases, as exemplified by the missions of the disease-
oriented institutes at the US National Institutes of Health (NIH, http://www.nih.gov) and
numerous national and international governmental and charitable organizations that support
medical research. The National Human Genome Research Institute (NHGRI), in budget terms a
rather small (less than 2%) component of the NIH, will work closely with all these organizations
in exploring and supporting these biomedical research capabilities. In addition, we envision a
more direct role for both the extramural and intramural programmes of the NHGRI in bringing a
genomic approach to the translation of genomic sequence information into health benefits.

The NHGRI brings two unique assets to this challenge. First, it has
close ties to a scientific community whose direct role over the past 13
years in bringing about the genomic revolution provides great
familiarity with its potential to transform biomedical research. Second,
the NHGRI's long-standing mission, to investigate the broadest
possible implications of genomics, allows unique flexibility to explore
the whole spectrum of human health and disease from the fresh
perspective of genome science. By engaging the energetic and
interdisciplinary genomics-research community more directly in
health-related research and by exploiting the NHGRI's ability to pursue
opportunities across all areas of human biology, the institute seeks to
participate directly in translating the promises of the HGP into
improved human health.

To fully achieve this goal, the NHGRI must also continue in its vigorous support of another of its
vital missions — the coupling of its scientific research programme with research into the social
consequences of increased availability of new genetic technologies and information. Translating
the success of the HGP into medical advances intensifies the need for proactive efforts to ensure
that benefits are maximized and harms minimized in the many dimensions of human experience.

A reader's guide

The vision for genomics research detailed here is the outcome of almost two years of intense
discussions with hundreds of scientists and members of the public, in more than a dozen
workshops and numerous individual consultations (see
http://www.genome.gov/About/Planning). The vision is formulated into three major themes —
genomics to biology, genomics to health, and genomics to society — and six crosscutting
elements.

We envisage the themes as three floors of a building, firmly resting on the foundation of the
HGP (Figure 2). For each theme, we present a series of grand challenges, in the spirit of the
proposals put forward for mathematics by David Hilbert at the turn of the twentieth century18.
These grand challenges are intended to be bold, ambitious research targets for the scientific
community. Some can be planned on specific timescales, others are less amenable to that level of
precision. We list the grand challenges in an order that makes logical sense, not representing
priority. The challenges are broad in sweep, not parochial — some can be led by the NHGRI
alone, whereas others will be best pursued in partnership with other organizations. Below, we
clarify areas in which the NHGRI intends to play a leading role.
Figure 2: The future of genomics rests on the foundation of the Human Genome Project.

The six critically important crosscutting

elements are relevant to all three thematic
areas. They are: resources (Box 1);
technology development (Box 2);
computational biology (Box 3); training
(Box 4); ethical, legal and social
implications (ELSI, Box 5); and education
(Box 6). We also stress the critical
importance of early, unfettered access to
genomic data in achieving maximum public
benefit. Finally, we propose a series of
'quantum leaps', achievements that would
lead to substantial advances in genomics
research and its applications to medicine. Some of these may seem overly bold, but no laws of
physics need to be violated to achieve them. Such leaps would have profound implications, just
as the dreams of the mid-1980s about the complete sequence of the human genome have been
realized in the accomplishments now being celebrated.

I Genomics to biology

Elucidating the structure and function of genomes

The broadly available genome sequences of human and a select set of additional organisms
represent foundational information for biology and biomedicine. Embedded within this as-yet
poorly understood code are the genetic instructions for the entire repertoire of cellular
components, knowledge of which is needed to unravel the complexities of biological systems.
Elucidating the structure of genomes and identifying the function of the myriad encoded
elements will allow connections to be made between genomics and biology and will, in turn,
accelerate the exploration of all realms of the biological sciences.

For this, new conceptual and technological approaches will be needed to:

 Develop a comprehensive and comprehensible catalogue of all of the components encoded in

the human genome.
 Determine how the genome-encoded components function in an integrated manner to perform
cellular and organismal functions.
 Understand how genomes change and take on new functional roles.

Grand Challenge I-1

Comprehensively identify the structural and functional components encoded in the human
genome
Although DNA is relatively simple and well understood chemically, the human genome's
structure is extraordinarily complex and its function is poorly understood. Only 1–2% of its
bases encode proteins7, and the full complement of protein-coding sequences still remains to be
established. A roughly equivalent amount of the non-coding portion of the genome is under
active selection11, suggesting that it is also functionally important, yet vanishingly little is known
about it. It probably contains the bulk of the regulatory information controlling the expression of
the approximately 30,000 protein-coding genes, and myriad other functional elements, such as
non-protein-coding genes and the sequence determinants of chromosome dynamics. Even less is
known about the function of the roughly half of the genome that consists of highly repetitive
sequences or of the remaining non-coding, non-repetitive DNA.

The next phase of genomics is to catalogue, characterize and comprehend the entire set of
functional elements encoded in the human and other genomes. Compiling this genome 'parts list'
will be an immense challenge. Well-known classes of functional elements, such as protein-
coding sequences, still cannot be accurately predicted from sequence information alone. Other
types of known functional sequences, such as genetic regulatory elements, are even less well
understood; undoubtedly new types remain to be defined, so we must be ready to investigate
novel, perhaps unexpected, ways in which DNA sequence can confer function. Similarly, a better
understanding of epigenetic changes (for example, methylation and chromatin remodelling) is
needed to comprehend the full repertoire of ways in which DNA can encode information.

Comparison of genome sequences from evolutionarily diverse species has emerged as a powerful
tool for identifying functionally important genomic elements. Initial analyses of available
vertebrate genome sequences7, 11, 19 have revealed many previously undiscovered protein-coding
sequences. Mammal-to-mammal sequence comparisons have revealed large numbers of
homologies in non-coding regions11, few of which can be defined in functional terms. Further
comparisons of sequences derived from multiple species, especially those occupying distinct
evolutionary positions, will lead to significant refinements in our understanding of the functional
importance of conserved sequences20. Thus, the generation of additional genome sequences from
several well-chosen species is crucial to the functional characterization of the human genome
(Box 1). The generation of such large sequence data sets will benefit from further advances in
sequencing technology that yield significant cost reductions (Box 2). The study of sequence
variation within species will also be important in defining the functional nature of some
sequences (see Grand Challenge I-3).

Effective identification and analysis of functional genomic elements will require increasingly
powerful computational capabilities, including new approaches for tackling ever-growing and
increasingly complex data sets and a suitably robust computational infrastructure for housing,
accessing and analysing those data sets (Box 3). In parallel, investigators will need to become
increasingly adept in dealing with this treasure trove of new information (Box 4). As a better
understanding of genome function is gained, refined computational tools for de novo prediction
of the identity and behaviour of functional elements should emerge21.

Complementing the computational detection of functional elements will be the generation of

additional experimental data by high-throughput methodologies. One example is the production
of full-length complementary DNA (cDNA) sequences (see, for example, http://mgc.nci.nih.gov
and http://www.fruitfly.org/EST/full.shtml). Major challenges inherent in programmes to
discover genes are the experimental identification and validation of alternate splice forms and
messenger RNAs expressed in a highly restricted fashion. Even more challenging is the
experimental validation of functional elements that do not encode protein (for example,
regulatory regions and non-coding RNA sequences). High-throughput approaches to identify
them (Box 2) will be needed to generate the experimental data that will be necessary to develop,
confirm and enhance computational methods for detecting functional elements in genomes.

Because current technologies cannot yet identify all functional elements, there is a need for a
phased approach in which new methodologies are developed, tested on a pilot scale and finally
applied to the entire human genome. Along these lines, the NHGRI recently launched the
Encyclopedia of DNA Elements (ENCODE) Project
(http://www.genome.gov/Pages/Research/ENCODE) to identify all the functional elements in the
human genome. In a pilot project, systematic strategies for identifying all functionally important
genomic elements will be developed and tested using a selected 1% of the human genome.
Parallel projects involving well-studied model organisms, for example, yeast, nematode and
fruitfly, are ongoing. The lessons learned will serve as the basis for implementing a broader
programme for the entire human genome.

Grand Challenge I-2

Elucidate the organization of genetic networks and protein pathways and establish how they
contribute to cellular and organismal phenotypes

Genes and gene products do not function independently, but participate in complex,
interconnected pathways, networks and molecular systems that, taken together, give rise to the
workings of cells, tissues, organs and organisms. Defining these systems and determining their
properties and interactions is crucial to understanding how biological systems function. Yet these
systems are far more complex than any problem that molecular biology, genetics or genomics
has yet approached. On the basis of previous experience, one effective path will begin with the
study of relatively simple model organisms22, such as bacteria and yeast, and then extend the
early findings to more complex organisms, such as mouse and human. Alternatively, focusing on
a few well-characterized systems in mammals will be a useful test of the approach (see, for
example, http://www.signaling-gateway.org).

Understanding biological pathways, networks and molecular systems will require information
from several levels. At the genetic level, the architecture of regulatory interactions will need to
be identified in different cell types, requiring, among other things, methods for simultaneously
monitoring the expression of all genes in a cell12. At the gene-product level, similar techniques
that allow in vivo, real-time measurement of protein expression, localization, modification and
activity/kinetics will be needed (Box 2). It will be important to develop, refine and scale up
techniques that modulate gene expression, such as conventional gene-knockout methods23, newer
knock-down approaches24 and small-molecule inhibitors25 to establish the temporal and cellular
expression pattern of individual proteins and to determine the functions of those proteins. This is
a key first step towards assigning all genes and their products to functional pathways.
The ability to monitor all proteins in a cell simultaneously would profoundly improve our ability
to understand protein pathways and systems biology. A critical step towards gaining a complete
understanding of systems biology will be to take an accurate census of the proteins present in
particular cell types under different physiological conditions. This is becoming possible in some
model systems, such as microorganisms26. It will be a major challenge to catalogue proteins
present in low abundance or in membranes. Determining the absolute abundance of each protein,
including all modified forms, will be an important next step. A complete interaction map of the
proteins in a cell, and their cellular locations, will serve as an atlas for the biological and medical
explorations of cellular metabolism27 (see http://www.nrcam.uchc.edu, for example). These and
other related areas constitute the developing field of proteomics.

Establishing a true understanding of how organized molecular pathways and networks give rise
to normal and pathological cellular and organismal phenotypes will require more than large,
experimentally derived data sets. Once again, computational investigation will be essential (Box
3), and there will be a greatly increased need for the collection, storage and display of the data in
robust databases. By modelling specific pathways and networks, predicting how they affect
phenotype, testing hypotheses derived from these models and refining the models based on new
experimental data, it should be possible to understand more completely the difference between a
'bag of molecules' and a functioning biological system.

Grand Challenge I-3

Develop a detailed understanding of the heritable variation in the human genome

Genetics seeks to correlate variation in DNA sequence with phenotypic differences (traits). The
greatest advances in human genetics have been made for traits associated with variation in a
single gene. But most phenotypes, including common diseases and variable responses to
pharmacological agents, have a more complex origin, involving the interplay between multiple
genetic factors (genes and their products) and non-genetic factors (environmental influences).
Unravelling such complexity will require both a complete description of the genetic variation in
the human genome and the development of analytical tools for using that information to
understand the genetic basis of disease.

Establishing a catalogue of all common variants in the human population, including single-
nucleotide polymorphisms (SNPs), small deletions and insertions, and other structural
differences, began in earnest several years ago. Many SNPs have been identified28, and most are
publicly available (http://www.ncbi.nlm.nih.gov/SNP). A public collaboration, the International
HapMap Project (http://www.genome.gov/Pages/Research/HapMap), was formed in 2002 to
characterize the patterns of linkage disequilibrium and haplotypes across the human genome and
to identify subsets of SNPs that capture most of the information about these patterns of genetic
variation to enable large-scale genetic association studies. To reach fruition, such studies need
more robust experimental (Box 2) and computational (Box 3) methods that use this new
knowledge of human haplotype structure29.

A comprehensive understanding of genetic variation, both in humans and in model organisms,

would facilitate studies to establish relationships between genotype and biological function. The
study of particular variants and how they affect the functioning of specific proteins and protein
pathways will yield important new insights about physiological processes in normal and disease
states. An enhanced ability to incorporate information about genetic variation into human genetic
studies would usher in a new era for investigating the genetic bases of human disease and drug
response (see Grand Challenge II-1).

Grand Challenge I-4

Understand evolutionary variation across species and the mechanisms underlying it

The genome is a dynamic structure, continually subjected to modification by the forces of

evolution. The genomic variation seen in humans represents only a small glimpse through the
larger window of evolution, where hundreds of millions of years of trial-and-error efforts have
created today's biosphere of animal, plant and microbial species. A complete elucidation of
genome function requires a parallel understanding of the sequence differences across species and
the fundamental processes that have sculpted their genomes into the modern-day forms.

The study of inter-species sequence comparisons is important for identifying functional elements
in the genome (see Grand Challenge I-1). Beyond this illuminating role, determining the
sequence differences between species will provide insight into the distinct anatomical,
physiological and developmental features of different organisms, will help to define the genetic
basis for speciation and will facilitate the characterization of mutational processes. This last point
deserves particular attention, because mutation both drives long-term evolutionary change and is
the underlying cause of inherited disease. The recent finding that mutation rates vary widely
across the mammalian genome11 raises numerous questions about the molecular basis for these
evolutionary changes. At present, our understanding of DNA mutation and repair, including the
important role of environmental factors, is limited.

Genomics will provide the ability to substantively advance insight into evolutionary variation,
which will, in turn, yield new insights into the dynamic nature of genomes in a broader
evolutionary framework.

Grand Challenge I-5

Develop policy options that facilitate the widespread use of genome information in both research
and clinical settings

Realization of the opportunities provided by genomics depends on effective access to the

information (such as data about genes, gene variants, haplotypes, protein structures, small
molecules and computational models) by a wide range of potential users, including researchers,
commercial enterprises, health-care providers, patients and the public. Researchers themselves
need maximum access to the data as soon as possible (see 'Data release', below). Use of the
information for the development of therapeutic and other products necessarily entails
consideration of the complex issues of intellectual property (for example, patenting and
licensing) and commercialization. The intellectual property practices, laws and regulations that
affect genomics must adhere to the principle of maximizing public benefit, but must also be
consistent with more general and longer-established intellectual property principles. Further,
because genome research is global, international treaties, laws, regulations, practices, belief
systems and cultures also come into play.

Without commercialization, most diagnostic and therapeutic advances will not reach the clinical
setting, where they can benefit patients. Thus, we need to develop policy options for data access
and for patenting, licensing and other intellectual property issues to facilitate the dissemination
of genomics data.

Top of page

II Genomics to health

Translating genome-based knowledge into health benefits

The sequencing of the human genome, along with other recent and expected achievements in
genomics, provides an unparalleled opportunity to advance our understanding of the role of
genetic factors in human health and disease, to allow more precise definition of the non-genetic
factors involved, and to apply this insight rapidly to the prevention, diagnosis and treatment of
disease. The report by the US National Research Council that originally envisioned the HGP was
explicit in its expectation that the human genome sequence would lead to improvements in
human health, and subsequent five-year plans reaffirmed this view15, 16, 17. But how this will
happen has been less clearly articulated. With the completion of the original goals of the HGP,
the time is right to develop and apply large-scale genomic strategies to empower improvements
in human health, while anticipating and avoiding potential harm.

Such strategies should enable the research community to achieve the following:

 Identify genes and pathways with a role in health and disease, and determine how they interact
with environmental factors.
 Develop, evaluate and apply genome-based diagnostic methods for the prediction of
susceptibility to disease, the prediction of drug response, the early detection of illness and the
accurate molecular classification of disease.
 Develop and deploy methods that catalyse the translation of genomic information into
therapeutic advances.

Grand Challenge II-1

Develop robust strategies for identifying the genetic contributions to disease and drug response

For common diseases, the interplay of multiple genes and multiple non-genetic factors, not a
single allele, usually dictates disease susceptibility and response to treatments. Deciphering the
role of genes in human health and disease is a formidable problem for many reasons, including
impediments to defining biologically valid phenotypes, challenges in identifying and quantifying
environmental exposures, technological obstacles to generating sufficient and useful genotypic
information, and the difficulties of studying humans. Yet this problem can be solved. Vigorous
development of crosscutting genomic tools to catalyse advances in understanding the genetics of
common disease and in pharmacogenomics is needed. Prominent among these will be a detailed
haplotype map of the human genome (see Grand Challenge I-3) that can be used for whole-
genome association studies of all diseases in all populations, as well as further advances in
sequencing and genotyping technology to make such studies feasible (see 'Quantum leaps',
below).

More efficient strategies for detecting rare alleles involved in common disease are also needed,
as the hypothesis that alleles that increase risk for common diseases are themselves common30
will probably not be universally true. Computational and experimental methods to detect gene–
gene and gene–environment interactions, as well as methods allowing interfacing of a variety of
relevant databases, are also required (Box 3). By obtaining unbiased assessments of the relative
disease risk that particular gene variants contribute, a large longitudinal population-based cohort
study, with collection of extensive clinical information and ongoing follow-up, would be
profoundly valuable to the study of all common diseases (Box 1). Already, such projects as the
UK Biobank (http://www.ukbiobank.ac.uk), the Marshfield Clinic's Personalized Medicine
Research Project (http://www.mfldclin.edu/pmrp) and the Estonian Genome Project
(http://www.geenivaramu.ee) seek to provide such resources. But if the multiple population
groups in the United States and elsewhere in the world are to benefit fully and fairly from such
research (see Grand Challenge II-6), a large population-based cohort study that includes full
representation of minority populations is also needed.

Grand Challenge II-2

Develop strategies to identify gene variants that contribute to good health and resistance to
disease

Most human genetic research has traditionally focused on identifying genes that predispose to
illness. A relatively unexplored, but important, area of research focuses on the role of genetic
factors in maintaining good health. Genomics will facilitate further understanding of this aspect
of human biology and allow the identification of gene variants that are important for the
maintenance of health, particularly in the presence of known environmental risk factors. One
useful research resource would be a 'healthy cohort', a large epidemiologically robust group of
individuals (Box 1) with unusually good health, who could be compared with cohorts of
individuals with diseases and who could also be intensively studied to reveal alleles protective
for conditions such as diabetes, cancer, heart disease and Alzheimer's disease. Another promising
approach would be rigorous examination of genetic variants in individuals at high risk for
specific diseases who do not develop them, such as sedentary, obese smokers without heart
disease or individuals with HNPCC mutations who do not develop colon cancer.

Grand Challenge II-3

Develop genome-based approaches to prediction of disease susceptibility and drug response,

early detection of illness, and molecular taxonomy of disease states

The discovery of variants that affect risk for disease could potentially be used in individualized
preventive medicine — including diet, exercise, lifestyle and pharmaceutical intervention — to
maximize the likelihood of staying well. For example, the discovery of variants that correlate
with successful outcomes of drug therapy, or with unfortunate side effects, could potentially be
rapidly translated into clinical practice. Turning this vision into reality will require the following:
(1) unbiased determination of the risk associated with a particular gene variant, often
overestimated in initial studies31; (2) technological advances to reduce the cost of genotyping
(Box 2; see 'Quantum leaps', below); (3) research on whether this kind of personalized genomic
information will actually alter health behaviours (see Grand Challenge II-5); (4) oversight of the
implementation of genetic tests to ensure that only those with demonstrated clinical validity are
applied outside of the research setting (Box 5); and (5) education of healthcare professionals and
the public to be well-informed participants in this new form of preventive medicine (Box 6).

The time is right for a focused effort to understand, and potentially to reclassify, all human
illnesses on the basis of detailed molecular characterization. Systematic analyses of somatic
mutations, epigenetic modifications, gene expression, protein expression and protein
modification should allow the definition of a new molecular taxonomy of illness, which would
replace our present, largely empirical, classification schemes and advance both disease
prevention and treatment. The reclassification of neuromuscular diseases32 and certain types of
cancer33 provides striking initial examples, but many more such applications are possible.

Such a molecular taxonomy would be the basis for the development of better methods for the
early detection of disease, which often allows more effective and less costly treatments.
Genomics and other large-scale approaches to biology offer the potential for developing new
tools to detect many diseases earlier than is currently feasible. Such 'sentinel' methods might
include analysis of gene expression in circulating leukocytes, proteomic analysis of body fluids,
and advanced molecular analysis of tissue biopsies. An example would be the analysis of gene
expression in peripheral blood leukocytes to predict drug response. A focused effort to use a
genomic approach to characterize serum proteins exhaustively in health and disease might also
be highly rewarding.

Grand Challenge II-4

Use new understanding of genes and pathways to develop powerful new therapeutic approaches
to disease

Pharmaceuticals on the market target fewer than 500 human gene products34. Even though not all
of the 30,000 or so human protein-coding genes7 will have products targetable for drug
development, this suggests that there is an enormous untapped pool of human gene-based targets
for therapeutic intervention. In addition, the new understanding of biological pathways provided
by genomics (see Grand Challenge I-2) should contribute even more fundamentally to
therapeutic design.

The information needed to determine the therapeutic potential of a gene generally overlaps
heavily with the information that reveals its function. The success of imatinib mesylate
(Gleevec), an inhibitor of the BCR-ABL tyrosine kinase, in treating chronic myelogenous
leukaemia relied on a detailed molecular understanding of the disease's genetic cause35. This
example offers promise that therapies based on genomic information will be particularly
effective. Grand Challenge I-1 describes the 'functionation' of the genome, which will
increasingly be the critical first step in the development of new therapeutics. But stimulating
basic scientists to approach biomedical problems with a genomic attitude is not enough. A
therapeutic mindset, lacking in much of academic biomedical research and training, must be
explicitly encouraged, and tools developed and provided for its implementation.

A particularly promising example of the gene-based approach to therapeutics is the application

of 'chemical genomics'25. This strategy uses libraries of small molecules (natural compounds,
aptamers or the products of combinatorial chemistry) and high-throughput screening to advance
understanding of biological pathways and to identify compounds that act as positive or negative
regulators of individual gene products, pathways or cellular phenotypes. Although the
pharmaceutical industry applies this approach widely as the first step in drug development, few
academic investigators have access to this methodology or are familiar with its use.

Providing such access more broadly, through one or more centralized facilities, could lead to the
discovery of a host of useful probes for biological pathways that would serve as new reagents for
basic research and/or starting points for the development of new therapeutic agents (the 'hits'
from such library screens will generally require medicinal chemistry modifications to yield
therapeutically usable compounds).

Also needed are new, more powerful technologies for generating deep molecular libraries,
especially ones tagged to allow the ready determination of precise molecular targets. A
centralized database of screening results should lead to further important biological insights.
Generating molecular probes for exploring the basic biology of health and disease in academic
laboratories would not supplant the major role of biopharmaceutical companies in drug
development, but could contribute to the start of the drug development pipeline. The private
sector would doubtless find many of these molecular probes of interest for further exploration
through optimization by medicinal chemistry, target validation, lead compound identification,
toxicological studies and, ultimately, clinical trials.

Academic pursuit of this first step in drug development could be particularly valuable for the
many rare mendelian diseases, in which often the gene defect is known but the small market size
limits the private sector's motivation to shoulder the expense of effective pharmaceutical
development. Such translational research in academic laboratories, combined with incentives
such as the US Orphan Drug Act, could profoundly increase the availability of effective
treatments for rare genetic diseases in the next decade. Further, the development of therapeutic
approaches to single-gene disorders might provide valuable insights into applying genomics to
reveal the biology of more common disorders and developing more effective treatments for them
(in the way that, for example, the search for compounds that target the presenilins has led to
general therapeutic strategies for late-onset Alzheimer's disease36).

Grand Challenge II-5

Investigate how genetic risk information is conveyed in clinical settings, how that information
influences health strategies and behaviours, and how these affect health outcomes and costs
Understanding how genetic factors affect health is often cited as a major goal of genomics, on
the assumption that applying such understanding in the clinical setting will improve health. But
this assumption actually rests on relatively few examples and data, and more research is needed
to provide sufficient guidance about how to use genomic information optimally for improving
individual or public health.

Theoretically, the steps by which genetic risk information would lead to improved health are: (1)
an individual obtains genome-based information about his/her own health risks; (2) the
individual uses this information to develop an individualized prevention or treatment plan; (3)
the individual implements that plan; (4) this leads to improved health; and (5) healthcare costs
are reduced. Scrutiny of these assumptions is needed, both to test them and to determine how
each step could best be accomplished in different clinical settings.

Research is also required that critically evaluates new genetic tests and interventions in terms of
parameters such as benefits, access and cost. Such research should be interdisciplinary and use
the tools and expertise of many fields, including genomics, health education, health behaviour
research, health outcomes research, healthcare delivery analysis, and healthcare economics.
Some of these fields have historically paid little attention to genomics, but high-quality research
of this sort could provide important guidance in clinical decision-making — as the work of
several disciplines has already been helpful in caring for people with an increased risk of colon
cancer as a result of mutations in FAP or HNPCC 37.

Grand Challenge II-6

Develop genome-based tools that improve the health of all

Disparities in health status constitute a significant global issue, but can genome-based
approaches to health and disease help to reduce this problem? Social and other environmental
factors are major contributors to health disparities; indeed, some would question whether
heritable factors have any significant role. But population differences in allele frequencies for
some disease-associated variants could be a contributing factor to certain disparities in health
status, so incorporating this information into preventive and/or public-health strategies would be
beneficial. Research is needed to understand the relationship between genomics and health
disparities by rigorously evaluating the diverse contributions of socioeconomic status, culture,
discrimination, health behaviours, diet, environmental exposures and genetics.

It is also important to explore applications of genomics in the improvement of health in the

developing world (http://www3.who.int/whosis/genomics/genomics_report.cfm), where both
human and non-human genomics will play significant roles. If we take malaria as an example, a
better understanding of human genetic factors that influence susceptibility and response to the
disease, and to the drugs used to treat it, could have a significant global impact. So too could a
better understanding of the malarial parasite itself and of its mosquito vector, which the recently
reported genome sequences38, 39 should provide. It will be necessary to determine the appropriate
roles of governmental and non-governmental organizations, academic institutions, industry and
individuals to ensure that genomics produces clinical benefits for resource-poor nations, and is
used to produce robust local research expertise.
To ensure that genomics research benefits all, it will be critical to examine how genomics-based
health care is accessed and used. What are the barriers to equitable access, and how can they be
removed? This is relevant not only in resource-poor nations, but also in wealthier countries
where segments of society, such as indigenous populations, the uninsured, or rural and inner city
communities, have traditionally not received adequate health care.

Top of page

III Genomics to society

Promoting the use of genomics to maximize benefits and minimize harms

Genomics has been at the forefront of giving serious attention, through scholarly research and
policy discussions, to the impact of science and technology on society. Although the major
benefits to be realized from genomics are in the area of health, as described above, genomics can
also contribute to other aspects of society. Just as the HGP and related developments have
spawned new areas of research in basic biology and in health, they have also created
opportunities for research on social issues, even to the extent of understanding more fully how
we define ourselves and each other.

In the next few years, society must not only continue to grapple with numerous questions raised
by genomics, but must also formulate and implement policies to address many of them. Unless
research provides reliable data and rigorous approaches on which to base such decisions, those
policies will be ill-informed and could potentially compromise us all. To be successful, this
research must encompass both 'basic' investigations that develop conceptual tools and shared
vocabularies, and more 'applied', 'translational' projects that use these tools to explore and define
appropriate public-policy options that incorporate diverse points of view.

As it has in the past, such research will continue to have important ramifications for all three
major themes of the vision presented here. We now address research that focuses on society
itself, more than on biology or health. Such efforts should enable the research community to:

 Analyse the impact of genomics on concepts of race, ethnicity, kinship, individual and group
identity, health, disease and 'normality' for traits and behaviours.
 Define policy options, and their potential consequences, for the use of genomic information and
for the ethical boundaries around genomics research.

Grand Challenge III-1

Develop policy options for the uses of genomics in medical and non-medical settings

Surveys have repeatedly shown that the public is highly interested in the concept that personal
genetic information might guide them to better health, but is deeply concerned about potential
misuses of that information (see http://www.publicagenda.org/issues/pcc_detail.cfm?
issue_type=medical_research&list=7). Topping the list of concerns is the potential for
discrimination in health insurance and employment. A significant amount of research on this
issue has been done40, policy options have been published41, 42, 43, and many US states have now
passed anti-discrimination legislation (see
http://www.genome.gov/Pages/PolicyEthics/Leg/StateIns and
http://www.genome.gov/Pages/PolicyEthics/Leg/StateEmploy). The US Equal Employment
Opportunity Commission has ruled that the Americans with Disabilities Act should apply to
discrimination based on predictive genetic information44, but the legal status of that construct
remains in some doubt. Although an executive order protects US government employees against
genetic discrimination, this does not apply to other workers. Thus, many observers have
concluded that effective federal legislation is needed, and the US Congress is currently
considering such a law.

Making certain that genetic tests offered to the public have established clinical validity and
usefulness must be a priority for future research and policy making. In the United States, the
Secretary's Advisory Committee on Genetic Testing extensively reviewed this area and
concluded that further oversight is needed, asking the Food and Drug Administration to review
new predictive genetic tests prior to marketing
(http://www4.od.nih.gov/oba/sacgt/reports/oversight_report.pdf). That recommendation has not
yet been acted on; meanwhile, numerous websites offering unvalidated genetic tests directly to
the public, often combined with the sale of 'nutraceuticals' and other products of highly
questionable value, are proliferating.

Many issues currently swirl around the proper conduct of genetic research involving human
subjects, and further work is needed to achieve a satisfactory balance between the protection of
research participants from harm and the ability to conduct clinical research that benefits society
as a whole. Much effort has gone into developing appropriate guidelines for the use of stored
tissue specimens (http://www.georgetown.edu/research/nrcbl/nbac/hbm.pdf), for community
consultation when conducting genetic research with identifiable populations
(http://www.nigms.nih.gov/news/reports/community_consultation.html#exec), and for the
consent of non-examined family members when conducting pedigree research
(http://www.nih.gov/sigs/bioethics/nih_third_party_rec.html), but confusion still remains for
many investigators and institutional review boards.

The use of genomic information is not limited to the arenas of biology and of health, and further
research and development of policy options is also needed for the many other applications of
such information. The array of additional users is likely to include the life, disability and long-
term care insurance industries, the legal system, the military, educational institutions and
adoption agencies. Although some of the research informing the medical uses of genomics will
be useful in broader settings, dedicated research outside the healthcare sphere is needed to
explore the public values that apply to uses of genomics other than for health care and their
relationship to specific contextual applications. For example, should genetic information on
predisposition to hyperactivity be available in the future to school officials? Or should genetic
information about behavioural traits be admissible in criminal or civil proceedings? Genomics
also provides greater opportunity to understand ancestral origins of populations and individuals,
which raises issues such as whether genetic information should be used for defining membership
in a minority group.
 Because uses of genomics outside the healthcare setting will involve a
significantly broader community of stakeholders, both research and
policy development in this area must involve individuals and
organizations besides those involved in the medical applications of
genomics. But many of the same perspectives essential to research and
policy development for the medical uses of genomics are also
essential. Both the potential users of non-medical applications of
genomics and the public need education to understand better the nature
and limits of genomic information (Box 6) and to grasp the ethical,
legal and social implications of its uses outside health care (Box 5).

Grand Challenge III-2

Understand the relationships between genomics, race and ethnicity,

and the consequences of uncovering these relationships

Race is a largely non-biological concept confounded by misunderstanding and a long history of

prejudice. The relationship of genomics to the concepts of race and ethnicity has to be considered
within complex historical and social contexts.

Most variation in the genome is shared between all populations, but certain alleles are more
frequent in some populations than in others, largely as a result of history and geography. Use of
genetic data to define racial groups, or of racial categories to classify biological traits, is prone to
misinterpretation. To minimize such misinterpretation, the biological and sociocultural factors
that interrelate genetics with constructs of race and ethnicity need to be better understood and
communicated within the next few years.

This will require research on how different individuals and cultures conceive of race, ethnicity,
group identity and self-identity, and what role they believe genes or other biological factors have.
It will also require a critical examination of how the scientific community understands and uses
these concepts in designing research and presenting findings, and of how the media report these.
Also necessary is widespread education about the biological meaning and limitations of research
findings in this area (Box 6), and the formulation and adoption of public-policy options that
protect against genomics-based discrimination or maltreatment (see Grand Challenge III-1).

Grand Challenge III-3

Understand the consequences of uncovering the genomic contributions to human traits and
behaviours

Genes influence not only health and disease, but also human traits and behaviours. Science is
only beginning to unravel the complicated pathways that underlie such attributes as handedness,
cognition, diurnal rhythms and various behavioural characteristics. Too often, research in
behavioural genetics, such as that regarding sexual orientation or intelligence, has been poorly
designed and its findings have been communicated in a way that oversimplifies and overstates
the role of genetic factors. This has caused serious problems for those who have been stigmatized
by the suggestion that alleles associated with what some people perceive as 'negative'
physiological or behavioural traits are more frequent in certain populations. Given this history
and the real potential for recurrence, it is particularly important to gather sufficient scientifically
valid information about genetic and environmental factors to provide a sound understanding of
the contributions and interactions between genes and environment in these complex phenotypes.

It is also important that there be robust research to investigate the implications, for both
individuals and society, of uncovering any genomic contributions that there may be to traits and
behaviours. The field of genomics has a responsibility to consider the social implications of
research into the genetic contributions to traits and behaviours, perhaps an even greater
responsibility than in other areas where there is less of a history of misunderstanding and
stigmatization. Decisions about research in this area are often best made with input from a
diverse group of individuals and organizations.

Grand Challenge III-4

Assess how to define the ethical boundaries for uses of genomics

Genetics and genomics can contribute understanding to many areas of biology, health and life.
Some of these human applications are controversial, with some members of the public
questioning the propriety of their scientific exploration. Although freedom of scientific inquiry
has been a cardinal feature of human progress, it is not unbounded. It is important for society to
define the appropriate and inappropriate uses of genomics. Conversations between diverse
parties based on an accurate and detailed understanding of the relevant science and ethical, legal
and social factors will promote the formulation and implementation of effective policies. For
instance, in reproductive genetic testing, it is crucial to include perspectives from the disability
community. Research should explore how different individuals, cultures and religious traditions
view the ethical boundaries for the uses of genomics — for instance, which sets of values
determine attitudes towards the appropriateness of applying genomics to such areas as
reproductive genetic testing, 'genetic enhancement' and germline gene transfer.

Top of page

Implementation: the NHGRI's role

The vision for the future of genomics presented here is broad and deep, and its realization will
require the efforts of many. Continuation of the extensive collaboration between scientists and
between funding sources that characterized the HGP will be essential. Although the NHGRI
intends to participate in all the research areas discussed here, it will need to focus its efforts to
use its finite resources as effectively as possible. Thus, it will take a major role in some areas,
actively collaborate in others, and have only a supporting role in yet others. The NHGRI's
priorities and areas of emphasis will also evolve as milestones are met and new opportunities
arise.
The approach that has characterized genomics and led to the success of the HGP — an initial
focus on technology development and feasibility studies, followed by pilot efforts to learn how
to apply new strategies and technologies efficiently on a larger scale, and then implementation of
full-scale production efforts — will continue to be at the heart of the NHGRI's priority-setting
process. The following are areas of high interest, not listed in priority order.

Large-scale production of genomic data sets

The NHGRI will continue to support genomic sequencing, focusing on the genomes of
mammals, vertebrates, chordates and invertebrates; other funders will support the determination
of additional genome sequences from microbes and plants. With current technology, the NHGRI
could support the determination of as much as 45–60 gigabases of genomic DNA sequence, or
the equivalent of 15–20 human genomes, over the next five years. But as the cost of sequencing
continues to decrease, the cost/benefit ratio of sequence generation will improve, so that the
actual amount of sequencing done will be greatly affected by the development of improved
sequencing technology.

The decisions about which genomes to sequence next will be based on the results of comparative
analyses that reveal the ability of genomic sequences from unexplored phylogenetic positions to
inform the interpretation of the human sequence and to provide other insights. Finally, the degree
to which any new genomic sequence is completed — finished, taken to an advanced draft stage
or lightly sampled — will be determined by the use for which the sequence is generated. And, of
course, the NHGRI's sequencing programme will maintain close contact with, and take account
of the plans and output of, other sequencing programmes, as has happened throughout the HGP.

A second data set ready for production-level effort is the human haplotype map (HapMap). This
project, a collaboration between the NHGRI, many other NIH institutes, and four international
partners, is scheduled for completion within three years. The outcome of the International
HapMap Project will significantly shape the future direction of the NHGRI's research efforts in
the area of genetic variation.

Pilot-scale efforts

The NHGRI has initiated the ENCODE Project to begin the development of the human genome
'parts list'. The first phase will address the application and improvement of existing technologies
for the large-scale identification of coding sequences, transcription units and other functional
elements for which technology is currently available. When the results of the ENCODE Project
show evidence of efficacy and affordability at the pilot scale, consideration will be given to
implementing the appropriate technologies across the entire human genome.

Technology development

Many areas of critical importance to the realization of the genomics-based vision for biomedical
research require new technological and methodological developments before pilots and then
large-scale approaches can be attempted. Recognizing that technology development is an
expensive and high-risk undertaking, the NHGRI is nevertheless committed to supporting and
fostering technology development in many of these crucial areas, including the following.

DNA sequencing. There is still great opportunity to reduce the cost and increase the throughput
of DNA sequencing, and to make rapid, cheap sequencing available more broadly. Radical
reduction of sequencing costs would lead to very different approaches to biomedical research.

Genetic variation. Improved genotyping methods and better mathematical methods are necessary
to make effective use of information about the structure of variation in the human genome for
identifying the genetic contributions to human diseases and other complex traits.

The genome 'parts list'. Beyond coding sequences and transcriptional units, new computational
and experimental approaches are needed to allow the comprehensive determination of all
sequence-encoded functional elements in genomes.

Proteomics. In the short term, the NHGRI expects to focus on the development of appropriate,
scalable technologies for the comprehensive analysis of proteins and protein machines in human
health and in both rare and complex diseases.

Pathways and networks. As a complement to the development of the genome 'parts list' and
increasingly effective approaches to proteome analysis, the NHGRI will encourage the
development of new technologies that generate a synthetic view of genetic regulatory networks
and interacting protein pathways.

Genetic contributions to health, disease and drug response. The NHGRI will place a high
priority on creating and applying new crosscutting genomics tools, technologies and strategies
needed to identify the genetic bases of medically relevant phenotypes. Research on the genetic
contributions to rare and common diseases, and to drug response, will typically involve
biological systems and diseases of primary interest to other NIH institutes and other funding
organizations. Accordingly, the NHGRI expects that its involvement in this area of research will
often be implemented through partnerships and collaborations. The NHGRI is particularly
interested in stimulating research approaches to the identification of gene variants that confer
disease resistance and other manifestations of 'good health'.

Molecular probes, including small molecules and RNA-mediated interference, for exploring
basic biology and disease. Exploration of the feasibility of expanding chemical genomics in the
academic and public sectors, particularly with regard to the establishment of one or more
centralized facilities, will be pursued by the NHGRI in partnership with others.

Databases

Another type of community resource for the biological and biomedical research communities is
represented by databases (Box 3). But their support represents a potentially significant problem.
Funding agencies, reflecting the interest of the research community, tend to prefer to use their
research funds to support the generation of new data, and the ongoing need for continued and
increasing support for the data archives and robust access to them is often given less attention.
Both the scientific community and the funding agencies must recognize that investment in the
creation and maintenance of effective databases is as important a component of research funding
as data generation. The NHGRI has been a major source of support for several major
genetics/genomics-oriented databases, including the Mouse Genome Database
(http://www.informatics.jax.org/mgihome/MGD/aboutMGD.shtml), the Saccharomyces Genome
Database (http://genome-www.stanford.edu/Saccharomyces), FlyBase
(http://flybase.bio.indiana.edu), WormBase (http://www.wormbase.org) and Online Mendelian
Inheritance in Man (http://www.ncbi.nlm.nih.gov/omim). The NHGRI will continue to be a
leader in exploring effective solutions to the issues of integrating, displaying and providing
access to genomic information.

Ethical, legal and social research

The NHGRI's ELSI research activities will increasingly focus on fundamental, widely relevant,
societal issues. The community of scholars and researchers working in these social fields, as well
as the scope of issues being explored, need to be expanded. The ELSI research community must
include individuals from minority and other communities that may be disproportionately affected
by the use or misuse of genetic information. New mechanisms for promoting dialogue and
collaboration between the ELSI researchers and genomic and clinical researchers need to be
developed; such examples might include structural rewards for interdisciplinary research,
intensive summer courses or mini-fellowships for cross-training, and the creation of centres of
excellence in ELSI studies to allow sustained interdisciplinary collaboration.

Longitudinal population cohort(s)

This promising research resource will be so broadly applicable, and will require such extensive
funding that, although the NHGRI might have a supporting role in design and oversight, success
will demand the involvement and support of many other funding sources.

Non-genetic factors in health and disease

A consequence of an improved definition of the genetic factors underlying human health and
disease will be an improvement in the recognition and definition of the environmental and other
non-genetic contributions to those traits. This is another area in which the NHGRI will be
involved through the development of new strategies and by forming partnerships.

Use of genomic information to improve health care

The NHGRI will catalyse collaboration between the diverse scholarly disciplines whose joint
efforts will be necessary for research on the best ways for patients and healthcare providers to
make effective use of personalized genetic information in the improvement of health. The
NHGRI will also strive to ensure that research in this area is informed by, and extends
knowledge of, the societal implications of genomics.
Improving the health of all people

It will be important for the NHGRI to support research that explores how to ensure that genomic
information is used, to the extent that such information is relevant, to reduce global health
disparities. That will include a vigorous effort to increase the representation of minorities in the
ranks of genomics researchers. But the full solution of the health disparities problem can only
come about through a committed and sustained effort by governments, medical systems and
society.

Policy development

The NHGRI will continue to help facilitate public-policy development in the area of
genetic/genomic science. Effective policy development will require attention to those issues for
which it could have the greatest impact on the policy agenda and could help to facilitate genomic
science. The NHGRI will also focus on issues that would assist the public in benefiting from
genomics, such as privacy of genetic information, access to genetics services, direct-to-
consumer/providers marketing, patenting and licensing of genetic information, appropriate
treatment of human participants in research, and standards, usefulness and quality in genetic
testing.

Top of page

Data release

An important lesson of the HGP has been the benefit of immediately releasing data from large-
scale sequencing projects, as embodied in the Bermuda principles
(http://www.gene.ucl.ac.uk/hugo/bermuda.htm). Some other large-scale data production projects
have followed suit (such as those for full-length cDNAs and single-nucleotide polymorphisms),
to the benefit of the scientific community. Scientific progress and public benefit will be
maximized by early, open and continuing access to large data sets and by ensuring that excellent
scientists are attracted to the task of producing more resources of this sort. For this system to
continue to work, the producers of community-resource data sets have an obligation to make the
results of their efforts rapidly available for free and unrestricted use by the scientific community,
and resource users have an obligation to recognize and respect the important contribution made
by the scientists who contribute their time and efforts to resource production.

Although these principles have been generally realized in the case of genomic DNA sequencing,
they have not been for many other types of community-resource projects (structural biology
coordinates or gene expression data, for example). The development of effective systems for
achieving the rapid release of data without restrictions and for providing continued widespread
access to materials and research tools should be an integral component of the planning and
development of new community resources. The scientific community should also develop
incentives to support the voluntary release of such data before publication by individual
investigators, by appropriately rewarding and protecting the interests of scientists who wish to
share their data with the community in such a generous manner.
Top of page

Quantum leaps

It is interesting to speculate about potential revolutionary technical developments that might

enhance research and clinical applications in a fashion that would rewrite entire approaches to
biomedicine. The advent of the polymerase chain reaction, large-insert cloning systems and
methods for low-cost, high-throughput DNA sequencing are examples of such advances that
have already occurred.

During the course of the NHGRI's planning discussions, other ideas were raised about analogous
'technological leaps' that seem so far off as to be almost fictional but which, if they could be
achieved, would revolutionize biomedical research and clinical practice.

The following is not intended to be an exhaustive list, but to provoke creative dreaming:

 the ability to determine a genotype at very low cost, allowing an association study in which
2,000 individuals could be screened with about 400,000 genetic markers for $10,000 or less;
 the ability to sequence DNA at costs that are lower by four to five orders of magnitude than the
current cost, allowing a human genome to be sequenced for $1,000 or less;
 the ability to synthesize long DNA molecules at high accuracy for $0.01 per base, allowing the
synthesis of gene-sized pieces of DNA of any sequence for between $10 and $10,000;
 the ability to determine the methylation status of all the DNA in a single cell; and
 the ability to monitor the state of all proteins in a single cell in a single experiment.

Top of page

Conclusions

Preparing a vision for the future of genomics research has been both daunting and exhilarating.
The willingness of hundreds of experts to volunteer their boldest and best ideas, to step outside
their areas of self-interest and to engage in intense debates about opportunities and priorities, has
added a richness and audacity to the outcome that was not fully anticipated when the planning
process began. To the extent that this article captures the sense of excitement of the new
discipline of genomics, it is to their credit. A complete list of the participants in this planning
process can be found at http://www.genome.gov/About/Vision/Acknowledgements.

A final word is appropriate about the breadth of the vision articulated

here. A choice had to be made between portraying a broad view of the
future of genomics research and focusing more narrowly on the
specific role of the NHGRI. Recognizing that researchers and the
public are more interested in the promise of the field than about the
funding source responsible, we have focused here on the broad
landscape of scientific opportunity. We have, however, identified the
areas that are particularly appropriate for leadership by the NHGRI
throughout this article. These are generally research areas that are not specific to a particular
disease or organ system, but have broader biomedical and/or social implications. Yet even in
those instances, the word 'partnership' appears numerous times intentionally. We expect to have
partnerships not only with other public funding sources, such as the other 26 NIH institutes and
centres, but also with many other governmental agencies, private foundations and private-sector
organizations. Indeed, public–private partnerships, such as the SNP Consortium, the Mouse
Sequencing Consortium and the International HapMap Project, provide powerful new models for
the generation of public data sets with immediate and far-reaching value. Thus, many of the most
exciting opportunities in genomics research cross traditional boundaries of specific disease
definitions, classically defined scientific disciplines, funding sources and public versus private
enterprise. The new era will flourish best in an environment where such traditional boundaries
become ever more porous.

Although the opportunities described here are thought to be highly achievable, the formal
initiation of specific programmes will require more detailed analysis. The relative priorities of
each component must be addressed in the light of limited resources to support research. The
NHGRI plans to release a revised programme announcement and other grant solicitations later
this year, providing more specific guidance to extramural researchers about plans for the
implementation of this vision. Furthermore, in genomics research, we have learned to expect the
unexpected. From past experience, it would be surprising (and rather disappointing) if biological,
medical and social contexts did not change in unpredictable ways. That reality requires that this
vision be revisited on a regular basis.

In conclusion, the successful completion this month of all of the original goals of the HGP
emboldens the launch of a new phase for genomics research, to explore the remarkable landscape
of opportunity that now opens up before us. Like Shakespeare, we are inclined to say, "what's
past is prologue" (The Tempest, Act II, Scene 1). If we, like bold architects, can design and build
this unprecedented and noble structure, resting on the firm bedrock foundation of the HGP
(Figure 2), then the true promise of genomics research for benefiting humankind can be realized.

"Make no little plans; they have no magic to stir men's blood and probably will themselves not
be realized. Make big plans; aim high in hope and work, remembering that a noble, logical
diagram once recorded will not die, but long after we are gone will be a living thing, asserting
itself with ever- growing insistency" (attributed to Daniel Burnham, architect).

Dalam Bahasa Indonesia

visi untuk masa depan dari genomic riset

franci s. collins<file: /h: \smad-lock\dna\nature01626. html>, eric d. green<file: /h: \smad-
lock\dna\nature01626. html>, alan e. guttmacher<file: /h: \smad-lock\dna\nature01626. html>
tanda s. guyer<file: /h: \smad-lock\dna\nature01626. html>
abstrak
cetak biru untuk genomic era.
kelengkapan dari high-quality, rangkaian lengkap manusia genome, di ini fiftieth tahun
tahunan penemuan double-helical struktur dna, peristiwa ciri khas. genomic era sekarang
kenyataan.
 di merenungkan visi untuk masa depan dari genomic riset, ini tepat menganggap jalan sempit
baik sekali yang telah membawa kita disini. rollfold (figur 1 <file: /h: \smad-
lock\dna\nature01626. html> menunjukkan timeline prestasi ciri khas di genetika dan genomic,
mulai dengan gregor mendel' penemuan hukum heredity<file: /h: \smad-lock\dna\nature01626.
html> dan mereka rediscovery pada awal hari abad ke duapuluh. pengakuan dna turun temurun
sebagai material<file: /h: \smad-lock\dna\nature01626. html>, determinasi structure<file: /h:
\smad-lock\dna\nature01626. html>, penyuluhan genetis code<file: /h: \smad-
lock\dna\nature01626. html>, pengembangan recombinant dna technologies5, <file: /h: \smad-
lock\dna\nature01626. html><file: /h: \smad-lock\dna\nature01626. html>, dan pendirian makin
bertambah automatable metode untuk dna sequencing7, <file: /h: \smad-lock\dna\nature01626.
html>8, <file: /h: \smad-lock\dna\nature01626. html>9, <file: /h: \smad-lock\dna\nature01626.
html>10 <file: /h: \smad-lock\dna\nature01626. html> seperangkat tingkatan untuk manusia
genome proyek (hgp mulai di 1990 (lihat juga <http: /www. alami. com/alami/dna50>.
terimakasih kepada visi perencana asli, dan kreatifitas dan determinasi legiun ilmuwan berbakat
yang memutuskan membuat proyek ini mereka melingkupi fokus, semua sasaran hasil awal hgp
punya sekarang mencapai sedikitnya dua tahun di depan harapan, dan revolusi di riset biologis
telah mulai.
figur 1: timeline <http: /www. alami. com/alami/majalah/v422/n6934/fig_tab/nature01626_f1.
html>

melihat lebih besar versi image ini download pdf <http: /www. alami.
com/alami/majalah/v422/n6934/pdf/timeline_01626. pdf> (1.9 m.
project' strategi riset baru dan teknologi percobaan telah membangkitkan sungai kokoh ever-
larger dan lebih rumit genomic kumpulan data yang telah menuangkan ke basis data umum dan
telah menjelma belajar dari sebenarnya semua hidup memproses. genomic mendekati
pengembangan teknologi dan generasi skala luas kumpulan data sumber komunitas telah
memperkenalkan dimensi baru penting ke biologis dan biomedical riset. interwoven kemajuan
dalam genetika, berdasarkan perbandingan genomic, high-throughput biokimia dan bioinformatic
membuktikan ahli ilmu biologi dengan dengan jelas memperbaiki acara yang tersedia alat-alat
riset yang akan mengizinkan berfungsi organisme di sehat dan penyakit untuk;menjadi meneliti
dan memahami belum pernah terjadi tingkat molekuler rinci. genome rangkaian, membatasi
satuan informasi yang penunjuk jalan pengembangan biologis dan fungsi, terletak berada di
pusat revolusi ini. singkatnya, genomic telah menjadi pusat dan gemblengan berpadu biomedical
riset.
akibat praktis kemunculan ladang baru ini meluas jelas. pengenalan gen bertanggung jawab
untuk manusia mendelian penyakit, sekali se tugas sangat kuat menuntut regu riset besar, banyak
tahun pekerjaan berat, dan hasil ragu-ragu, dapat sekarang routinely ulung dalam beberapa
minggu dengan pelajar lulusan tunggal dengan akses ke dna sederhana dan berasosiasi
phenotype, hubungan internet kepada umum genome basis data, termis cycler dan dna-
sequencing mesin. dengan penerbitan baru-baru ini rangkaian naskah tikus genome11 <file: /h:
\smad-lock\dna\nature01626. html>, pengenalan mutasi mendasari jumlah terbesar menarik tikus
phenotype punya dengan cara yang sama sangat menyederhanakan. bandingan manusia dan
rangkaian tikus menunjukkan bahwa bagian mammalian genome bawah pilihan evolusioner
lebih dari dua kali itu sebelumnya menganggap.
kemampuan kami menjelajahi genome fungsi meningkat di ketegasan sebagai setiap
kemudian genome sequenced. microarray teknologi telah catapulted banyak laboran dari belajar
ekspresi satu atau dua gen sebulan belajar ekspresi puluhan dari beribu-ribu gen di tunggal
afternoon12 <file: /h: \smad-lock\dna\nature01626. html>. klinis kesempatan untuk gene-based
pre-symptomatic ramalan keadaan sakit dan tanggapan narkoba kurang menguntungkan muncul
langkah cepat, dan mengobati memberi harapan dari genomic telah mengumumkan gelombang
rangsang ekspansi dan eksplorasi di komersial sector13 <file: /h: \smad-lock\dna\nature01626.
html>. investasi hgp di belajar etis, sah dan implikasi sosial kemajuan ilmiah ini telah
menciptakan sepasukan tentara berbakat sarjana di etika, hukum, ilmu sosial, riset klinis, ilmu
agama dan kebijaksanaan umum, dan punya telah menghasilkan di penting meningkat di
kesadaran umum dan pengenalan tentang signifikan (tetapi masih proteksi tidak sempurna)
melawan menyalahgunakan seperti diskriminasi genetis (lihat <http: /www. genome.
gov/policyethics>.
prestasi ini memenuhi visi luas melafalkan di 1988 laporan badan riset nasional, pemetaan
dan peruntunan manusia genome14 <file: /h: \smad-lock\dna\nature01626. html>. berhasil
kelengkapan hgp tahun ini jadi mewakili peluang melihat muka dan tawari cetak biru untuk masa
depan dari genomic riset dalam yang akan datang beberapa tahun.
visi menyajikan disini alamat berbeda dunia dari mencerminkan di rencana itu terdahulu
menerbitkan di 1990,1993 dan 1998 (ref -1517 <file: /h: \smad-lock\dna\nature01626. html>.
dokumen itu mengalamatkan tujuan 1988 laporan, melukiskan merinci jalan sempit ke arah
pengembangan genome-analysi teknologi, fisik dan pemetaan genetis genome, dan peruntunan
organisme contoh genome dan, akhirnya, manusia genome. sekarang, dengan efektif
kelengkapan dari tujuan ini, kami tawar lebih luas dan masih ada lagi visi ambisius, sesuai
dengan benar menyingsing genomic era. tantangan menggunakan modal di potensial tak terukur
hgp meningkatkan sehat manusia dan kesejahteraan.
artikulasi visi baru peluang menjelajahi transformative baru mendekati mencapai keuntungan
sehat. meskipun genome-based metode analisis dengan cepat menyebar keseluruh bagian
biomedical riset, tantangan menetapkan jalan sempit kuat dari genomic informasi memperbaiki
sisa sehat manusia tak terukur. usaha arus menjumpai tantangan ini sebagian besar
mengorganisir mengelilingi belajar penyakit khusus, sebagai dicontohkan oleh misi menyease-
oriented institut di kita institut nasional sehat (nih, <http: /www. nih. gov/> dan nasional banyak
dan internasional bidang pemerintah dan organisasi murah hati dukungan itu riset medis.
manusia nasional genome institut riset (nhgri, di syarat-syarat anggaran belanja lebih kecil
kurang dari 2% menjadikan lengkap nih, akan kerjakan dengan teliti dengan semua ini
organisasi di menyelidiki dan mendukung ini biomedical kemampuan riset. sebagai tambahan,
kami memimpikan banyak langsung peranan untuk keduanya diluar sekolah dan program
diantara dinding nhgri di membawa genomic mendekati kepada terjemahan genomic informasi
rangkaian ke keuntungan sehat.

nhgri membawa dua aktiva unik pada ini tantangan. pertama, ini telah menutup pertalian ke
komunitas ilmiah siapa punya langsung peranan melalui masa lalu 13 tahun di membawa tentang
genomic revolusi menyediakan keakraban besar dengan nya potensial mengubah bentuk
biomedical riset. kedua, nhgri' long-standing misi, menyelidiki paling luas mungkin implikasi
genomic, mengizinkan kelenturan unik menjelajahi spektrum keseluruhan sehat manusia dan
penyakit dari visi segar genome ilmu pengetahuan. oleh menarik bersemangat dan
interdisciplinary genomics-research komunitas banyak secara langsung di health-related riset dan
oleh memanfaatkan nhgri' kemampuan mengejar kesempatan melintasi semua wilayah biologi
manusia, institut mencarikan mengikuti secara langsung di menterjemahkan memberi harapan
hgp ke diperbaiki sehat manusia.
ke secara penuh mencapai gol ini, nhgri harus juga melanjutkan dalam nya dukungan giat
lainnya misi sangat penting - gandengan program riset ilmiah dengan me-riset akibat sosial
meningkat ketersediaan teknologi genetis baru dan informasi. menterjemahkan sukses hgp ke
kemajuan medis intensifie kebutuhan akan usaha proaktif memastikan bahwa keuntungan
dimaksimalkan dan rugikan memperkecil di banyak dimensi pengalaman manusia.
reader' penunjuk jalan
visi untuk genomic riset merinci disini hasil hampir dua tahun amat sangat bahasan dengan
beratus-ratus ilmuwan dan para anggota orang ban, di lebih dari selusin workshop dan konsultasi
sendiri banyak (lihat <http: /www. genome. gov/tentang/planning>. visi dijabarkan ke tiga tema
utama - genomic ke biologi, genomic ke sehat, dan genomic ke masyarakat - dan enam
crosscutting unsur.
kami memandang tema sebagai tiga lantai membangun, teguh beristirahat di pondasi bagi hgp
(figur 2 <file: /h: \smad-lock\dna\nature01626. html>. untuk setiap tema, kami hadirkan
tantangan besar satu rangkaian, di roh usul meletakkan muka untuk matematika dengan daud
hilbert di giliran yang keduapuluh century18 <file: /h: \smad-lock\dna\nature01626. html>.
tantangan besar ini dimaksudkan untuk tebal, sasaran-sasaran riset ambisius untuk komunitas
ilmiah. dapat bermaksud jadwal waktu khusus, lain kurang untuk itu bersedia menerima nasehat
tingkat ketepatan. kami daftar tantangan besar di pesanan itu membuat rasa logis, tidak mewakili
prioritas. tantangan luas di menyapu, tidak terbatas - dapat memimpin oleh nhgri sendirian,
sedangkan lain akan [jadi] mengejar di rekanan dengan organisasi terbaik lain. di bawah, kami
menjelaskan wilayah di mana nhgri bermaksud bermain memimpin peranan.
figur 2: masa depan dari genomic mempercayai pada; bersandarkan pondasi bagi manusia
genome proyek. <http: /www. alami. com/alami/majalah/v422/n6934/fig_tab/nature01626_f2.
html>

enam dengan kritis penting crosscutting unsur sesuai ke semua tiga thematic wilayah. mereka:
sumber daya (kotak 1 <http: /www. alami.
com/alami/majalah/v422/n6934/kotak/nature01626_bx1. html>; pengembangan teknologi (kotak
2 <http: /www. alami. com/alami/majalah/v422/n6934/kotak/nature01626_bx2. html>;
computational biologi (kotak 3 <http: /www. alami.
com/alami/majalah/v422/n6934/kotak/nature01626_bx3. html>; latihan (kotak 4 <http: /www.
alami. com/alami/majalah/v422/n6934/kotak/nature01626_bx4. html>; etis, sah dan implikasi
sosial (elsi, kotak 5 <http: /www. alami.
com/alami/majalah/v422/n6934/kotak/nature01626_bx5. html>; dan (kotak pendidikan 6
<http: /www. alami. com/alami/majalah/v422/n6934/kotak/nature01626_bx6. html>. kami juga
tekanan pentingnya kritis awal, akses tak terkekang ke genomic data dalam mencapai
pertolongan umum maksimum. akhirnya, kami menyarankan 'kuantum satu rangkaian
melompat', pencapaian itu akan mendorong kearah kemajuan dalam penting genomic riset dan
aplikasi nya ke obat. sebagian dari ini mungkin bampak sangat tebal, tetapi tidak hukum fisika
perlu untuk;menjadi tidak menghormati mencapai mereka. demikian melompat akan punya
implikasi mendalam, sama [halnya] mimpi mid-1980 tentang menyelesaikan rangkaian manusia
genome telah mewujudkan di prestasi sekarang sedang merayakan.
saya genomic ke biologi
 menerangkan struktur dan fungsi genome
dengan luas tersedia genome rangkaian manusia dan pilih satuan organisme tambahan
mewakili foundational informasi untuk biologi dan biomedicine. menanamkan dalam ini as-yet
mengerti kode kurang baik instruksi genetis untuk seluruh acara yang tersedia komponen
seluller, pengetahuan diperlukan ke lepas kompleksitas sistem biologis. menerangkan struktur
genome dan mengenali fungsi jumlah yang tidak terhitung menyandi unsur akan mengizinkan
koneksi untuk;menjadi membuat diantara genomic dan biologi dan akan, pada gilirannya,
percepat eksplorasi kerajaan pengetahuan biologis.
untuk ini, konseptual baru dan teknologi mendekati akan [jadi] memerlukan ke:
· mengembangkan lengkap dan katalog dapat dimengerti komponen menyandi di manusia
genome.
· menentukan bagaimana genome-encoded fungsi komponen di menggabungkan cara
melakukan seluller dan organismal fungsi.
· mengerti bagaimana genome merubah dan menerima peranan fungsional baru.
tantangan besar i-1
dengan penuh pemahaman mengenali membangun dan komponen fungsional menyandi di
manusia genome
meskipun dna secara relatif sederhana dan mengerti secara kimiawi baik, manusia genome'
struktur secara luar biasa gabungan dan fungsi nya mengerti kurang baik. hanya 1-2% tentang
nya basis menyandikan proteins<file: /h: \smad-lock\dna\nature01626. html>, dan pelengkap
penuh protein-coding rangkaian masih sisa untuk;menjadi mendirikan. secara kasar jumlah sama
non-coding bagian genome bawah giat selection11 <file: /h: \smad-lock\dna\nature01626. html>,
mengesankan bahwa juga secara fungsional penting, masih vanishingly kecil dikenal tentang itu.
ini mungkin berisi jumlah besar pengontrolan informasi pengaturan ekspresi kira-kira 30,000
protein-coding gen, dan jumlah yang tidak terhitung unsur, fungsional lain seperti non-protein-
coding gen dan determinan rangkaian dinamika kromosom. bahkan kurang dikenal tentang
fungsi secara kasar setengah genome itu terdiri dari sangat rangkaian berulang atau remaining
non-coding, non-repetitive dna.
berikut gelombang genomic ke katalog, watakkan dan pahami seluruh satuan unsur fungsional
menyandi di manusia dan lain genome. menyusun ini genome 'daftar bagian' akan merupakan
suatu tantangan tak terukur. kelas terkenal unsur fungsional, seperti protein-coding rangkaian,
masih tidak bisa dengan teliti meramalkan dari informasi rangkaian sendirian. tipe lain
mengetahui rangkaian fungsional, seperti unsur pengaturan genetis, bahkan kurang mengerti
baik; niscaya sisa tipe baru untuk;menjadi menggambarkan, kami harus siap menyelidiki novel,
barangkali tak diduga, cara dna rangkaian dapat menganugerahkan fungsi. dengan cara yang
sama, lebih baik kesepakatan epigenetic perubahan sebagai contoh, methylation dan chromatin
remodelling diperlukan memahami acara yang tersedia penuh cara dna dapat menyandikan
informasi.
bandingan genome rangkaian dari evolutionarily bermacam-macam spesies telah muncul
sebagai alat bertenaga untuk mengenali secara fungsional penting genomic unsur. awal meneliti
dari tersedia hewan bertulang belakang genome sequences7, <file: /h: \smad-
lock\dna\nature01626. html>11, <file: /h: \smad-lock\dna\nature01626. html>19 <file: /h: \smad-
lock\dna\nature01626. html> telah diwahyukan banyak sebelumnya undiscovered protein-coding
rangkaian. mammal-to-mammal bandingan rangkaian telah diwahyukan besar jumlah dari
homologie di non-coding regions11 <file: /h: \smad-lock\dna\nature01626. html>, beberapa
dimana dapat menggambarkan di syarat-syarat fungsional. lebih jauh bandingan rangkaian
menurunkan dari spesies kelipatan, khususnya itu menempati posisi evolusioner berbeda, akan
mendorong kearah signifikan pemurnian di kesepakatan kami pentingnya fungsional memelihara
sequences20 <file: /h: \smad-lock\dna\nature01626. html>. jadi, tambahan pembuatan genome
rangkaian dari beberapa spesies yang dipilih dengan baik kepada penting sekali perwatakan
fungsional manusia genome (kotak 1 <http: /www. alami.
com/alami/majalah/v422/n6934/kotak/nature01626_bx1. html>. pembuatan demikian kumpulan
data rangkaian besar akan pertolongan dari lebih jauh kemajuan dalam teknologi peruntunan
hasil itu signifikan berharga penurunan (kotak 2 <http: /www. alami.
com/alami/majalah/v422/n6934/kotak/nature01626_bx2. html>. belajar variasi rangkaian dalam
spesies akan juga penting di melukiskan alami fungsional rangkaian (lihat tantangan besar i-3.
pengenalan efektif dan analisis fungsional genomic unsur akan memerlukan makin bertambah
bertenaga computational kemampuan, termasuk baru mendekati untuk mengerjakan ever-
growing dan makin bertambah kumpulan data gabungan dan yang sesuai kuat computational
infrastruktur untuk perumahan, mengakses dan menganalisa kumpulan data itu (kotak 3 <http:
/www. alami. com/alami/majalah/v422/n6934/kotak/nature01626_bx3. html>. di sejajar,
pemeriksa akan perlu makin bertambah ahli di berhadapan dengan harta terpendam yang didapati
ini dari informasi baru (kotak 4 <http: /www. alami.
com/alami/majalah/v422/n6934/kotak/nature01626_bx4. html>. sebagai lebih baik kesepakatan
genome fungsi diganyang, menyuling computational alat-alat untuk tidak novo ramalan identitas
dan kelakuan dari unsur fungsional harus emerge21 <file: /h: \smad-lock\dna\nature01626.
html>.
melengkapi computational pendeteksi unsur fungsional akan menjadi generasi data percobaan
tambahan dengan high-throughput metodologi. satu contoh produksi full-length yang melengkapi
dna (cdna rangkaian (lihat, sebagai contoh, <http: /mgc. nci. nih. gov/> dan <http: /www. bari-
bari. org/est/penuh. shtml>. tidak dapat diceraikan tantangan utama di program menemukan gen
pengenalan percobaan dan pengesahan mengubah menyambung dengan menjalin bentuk dan
pesuruh rna terungkap di sangat membatasi gaya. lebih lagi menantang pengesahan percobaan
unsur fungsional yang tidak menyandikan protein sebagai contoh, wilayah pengaturan dan non-
coding rna rangkaian). high-throughput mendekati mengenali mereka (kotak 2 <http: /www.
alami. com/alami/majalah/v422/n6934/kotak/nature01626_bx2. html> akan [jadi] memerlukan
mengadakan data percobaan yang akan [jadi] perlu mengembangkan, konfirmasikan dan
memperbesar computational metode untuk mendeteksi unsur fungsional di genome.
karena teknologi arus tidak bisa masih mengenali semua unsur fungsional, ada suatu
kebutuhan untuk membuat bertahap mendekati di mana metodologi baru membangun, diuji di
skala penerbang dan akhirnya menerapkan kepada seluruh manusia genome. terus baris ini, nhgri
meluncurkan ensiklopedi dna unsur (menyandikan) proyek (<http baru-baru ini: /www. genome.
gov/halaman/riset/encode> mengenali semua unsur fungsional di manusia genome. di proyek
percobaan, strategi sistematik untuk mengenali semua secara fungsional penting genomic unsur
akan [jadi] membangun dan menguji menggunakan memilih 1% manusia genome. sejajar proyek
menyertakan well-studied organisme contoh, sebagai contoh, ragi, nematode dan bari-bari, terus
menerus. pelajaran belajar akan bertindak sebagai dasar untuk menerapkan program lebih luas
untuk seluruh manusia genome.
tantangan besar i-2
menerangkan organisasi jaringan genetis dan protein trotoar dan dirikan bagaimana mereka
berperan untuk seluller dan organismal phenotype
 gen dan produk gen tidak fungsi dengan bebas, tetapi berpartisipasilah di gabungan, saling
behubungan trotoar, jaringan dan sistem molekuler itu, mengambil bersama, beri kenaikan
kepada bekerja sel, tisu, organ dan organisme. melukiskan sistem ini dan menentukan kekayaan
mereka dan interaksi penting sekali ke kesepakatan bagaimana fungsi sistem biologis. sistem ini
masih jauh lebih rumit daripada beberapa masalah biologi molekuler itu, genetika atau genomic
punya mendekati masih. atas dasar sebelumnya pengalaman, satu jalan sempit efektif akan mulai
dengan belajar dari secara relatif contoh sederhana organisms22 <file: /h: \smad-
lock\dna\nature01626. html>, seperti bakteri dan ragi, dan kemudian perpanjang awal
menemukan ke organisme lebih rumit, seperti tikus dan manusia. sebagai alternatif, memusatkan
di beberapa well-characterized sistem di mamalia akan merupakan suatu percobaan berguna
mendekati (lihat, sebagai contoh, <http: /www. signaling-gateway. org/>.
kesepakatan trotoar biologis, jaringan dan sistem molekuler akan memerlukan informasi dari
beberapa tingkat. di genetis tingkat, arsitektur interaksi pengaturan akan perlu untuk;menjadi
mengenali di berbeda tipe sel, menuntut, di antaranya, metode untuk serempak mengawasi
ekspresi gen di cell12 <file: /h: \smad-lock\dna\nature01626. html>. di gene-product tingkat,
mirip teknik yang mengizinkan di vivo, real-time ukuran protein ekspresi, lokalisasi, perubahan
dan kegiatan/ilmu gerak akan [jadi] memerlukan (kotak 2 <http: /www. alami.
com/alami/majalah/v422/n6934/kotak/nature01626_bx2. html>. ini akan [jadi] penting
mengembangkan, bersih dan menaikkan teknik yang mengatur tinggi nada ekspresi gen, seperti
konversional gene-knockout methods23 <file: /h: \smad-lock\dna\nature01626. html>, lebih baru
memukul roboh approaches24 <file: /h: \smad-lock\dna\nature01626. html> dan small-molecule
inhibitors25 <file: /h: \smad-lock\dna\nature01626. html> mendirikan sementara dan pola
ekspresi seluller sendiri protein dan menentukan fungsi protein. ini adalah kunci pertama langkah
ke arah menugaskan semua gen dan produk mereka ke trotoar fungsional.
kemampuan ke monitor semua protein di sel serempak akan sangat meningkatkan
kemampuan kami mengerti protein trotoar dan biologi sistem. langkah kritis ke arah memperoleh
menyelesaikan kesepakatan biologi sistem adalah untuk mengambil sensus teliti protein hadir di
tipe sel teliti bawah berbeda kondisi fisiologis. ini adalah menjadi mungkin dalam beberapa
sistem contoh, seperti microorganisms26 <file: /h: \smad-lock\dna\nature01626. html>. ini akan
merupakan suatu tantangan utama ke katalog protein hadir di kelimpahan rendah atau di
membran. menentukan kelimpahan lengkap protein, termasuk semua bentuk dimodifikasi, akan
merupakan suatu penting berikut langkah. menyelesaikan interaksi dipetakan protein di sel, dan
lokasi seluller mereka, akan bertindak sebagai atlas untuk biologis dan eksplorasi medis seluller
metabolism27 <file: /h: \smad-lock\dna\nature01626. html> (lihat <http: /www. nrcam. uchc.
edu/>, untuk contoh). ini dan peraturan wilayah lain yang berhubungan mengembang ladang
proteomic.
menetapkan kesepakatan benar bagaimana mengorganisir trotoar molekuler dan jaringan
memberi kenaikan ke normal dan seluller berkenaan dengan penyakit dan organismal phenotype
akan memerlukan lebih dari besar, secara eksprimen menurunkan kumpulan data. sekali lagi,
computational pemeriksaan akan [jadi] (kotak pokok 3 <http: /www. alami.
com/alami/majalah/v422/n6934/kotak/nature01626_bx3. html>, dan akan ada sangat meningkat
perlu untuk koleksi, penyimpanan dan tampilan data di basis data kuat. dengan trotoar khusus
modeling dan jaringan, meramalkan bagaimana mereka mempengaruhi phenotype, hipotesis
ujian menurunkan dari model ini dan penghalusan model berdasarkan di data percobaan baru,
haruslah mungkin mengerti banyak selesai semua perbedaan diantara 'tas molekul' dan berfungsi
sistem biologis.
 tantangan besar i-3
kembangkan merinci kesepakatan variasi turun temurun di manusia genome
genetika mencarikan hubung variasi di dna rangkaian dengan phenotypic perbedaan (ciri).
kemajuan dalam terbesar genetika manusia telah membuat untuk ciri berasosiasi dengan variasi
di gen tunggal. tetapi paling phenotype, termasuk penyakit biasa dan variabel menjawab agen
pharmakologis, punya asal lebih rumit, menyertakan keadaan saling mempengaruhi diantara
kelipatan faktor genetis (gen dan produk mereka) dan non-genetic faktor (lingkungan
mempengaruhi). unravelling demikian keruwetan akan memerlukan keduanya menyelesaikan
deskripsi variasi genetis di manusia genome dan pengembangan alat-alat analitis untuk yang
menggunakan informasi itu mengerti dasar genetis penyakit.
menetapkan katalog varian-varian biasa di populasi manusia, termasuk single-nucleotide
polymorphism (snp, penghilangan kecil dan penyisipan, dan lain membangun perbedaan, mulai
dengan sungguh-sungguh beberapa tahun yang lalu. banyak snp telah identified28 <file: /h:
\smad-lock\dna\nature01626. html>, dan paling di depan umum tersedia (<http: /www. ncbi.
nlm. nih. gov/snp>. kerja sama umum, internasional hapmap proyek (<http: /www. genome.
gov/halaman/riset/hapmap>, dilengkungkan di 2002 menggambarkan pola ketakseimbangan
pertalian dan haplotype melintasi manusia genome dan mengenali subset dari snp itu menangkap
kebanyakan dari informasi tentang pola ini variasi genetis mengaktifkan skala luas persatuan
genetis belajar. mencapai tercapainya harapan, demikian belajar perlu banyak (kotak percobaan
kuat 2 <http: /www. alami. com/alami/majalah/v422/n6934/kotak/nature01626_bx2. html> dan
computational (kotak 3 <http: /www. alami.
com/alami/majalah/v422/n6934/kotak/nature01626_bx3. html> metode yang menggunakan
pengetahuan baru ini manusia haplotype structure29 <file: /h: \smad-lock\dna\nature01626.
html>.
kesepakatan lengkap variasi genetis, baik dalam manusia dan di organisme contoh, akan
memudahkan belajar mendirikan hubungan diantara genotype dan fungsi biologis. belajar dari
varian-varian teliti dan bagaimana mereka mempengaruhi berfungsi khusus protein dan protein
trotoar akan hasil kepandaian untuk memahami baru penting tentang fisiologis memproses di
normal dan negeri penyakit. kemampuan peningkatan mempersatukan informasi tentang variasi
genetis ke manusia genetis belajar akan mengumumkan era baru untuk menyelidiki basis genetis
penyakit manusia dan tanggapan narkoba (lihat tantangan besar ii-1.
tantangan besar i-4
pahami variasi evolusioner melintasi spesies dan mekanisme mendasari ini
genome struktur dinamis, secara terus menerus memperlakukan perubahan oleh kekuatan
evolusi. genomic variasi melihat di manusia mewakili hanya kecil memandang sekilas melalui
lebih besar jendela evolusi, dimana beratus juta tahun trial-and-error usaha telah menciptakan
biosfer masa kini hewan, tanaman dan microbial spesies. menyelesaikan penyuluhan genome
fungsi memerlukan sejajar kesepakatan perbedaan rangkaian melintasi spesies dan asasi
memproses telah memahat itu mereka genome ke bentuk jaman modern.
belajar dari inter-specie bandingan rangkaian penting untuk mengenali unsur fungsional di
genome (lihat tantangan besar i-1. di seberang ini memperjelas peranan, menentukan perbedaan
rangkaian diantara spesies akan menyediakan kepandaian untuk memahami ke anatomis berbeda,
fisiologis dan keistimewaan pengembangan organisme, akan membantu ke arah mengartikan
dasar genetis untuk speciation dan akan mudahkan perwatakan mutational memproses. poin lalu
ini perhatian teliti patut menerima, karena mutasi keduanya mengendarai evolusioner jangka
panjang merubah dan mendasari penyebab menerima warisan penyakit. temuan baru-baru ini
angka mutasi itu merubah meluas melintasi mammalian genome11 <file: /h: \smad-
lock\dna\nature01626. html> menaikkan pertanyaan banyak tentang dasar molekuler untuk
evolusioner ini perubahan. sekarang, kesepakatan kami dna mutasi dan perbaiki, termasuk
penting peranan faktor lingkungan, terbatas.
genomic akan menyediakan kemampuan ke sebenarnya kepandaian untuk memahami
kemajuan ke variasi evolusioner, yang akan, pada gilirannya, hasil kepandaian untuk memahami
baru ke alami dinamis genome di rangka evolusioner lebih luas.
tantangan besar i-5
kembangkan pilihan kebijakan yang memudahkan tersebar menggunakan dari genome
informasi di keduanya riset dan klinis penyesuaian
pelaksanaan kesempatan menyediakan oleh genomic bergantung di akses efektif kepada
informasi seperti data tentang gen, varian-varian gen, haplotype, protein struktur, molekul kecil
dan computational model) dengan cakupan luas dari pengguna potensial, termasuk peneliti,
perseroan komersial, health-care provider, sabar dan orang ban. mereka sendiri peneliti perlu
akses maksimum kepada data secepat mungkin (lihat 'data mengeluarkan', di bawah). gunakan
informasi untuk pengembangan mengobati dan produk lain perlu menyebabkan perlu ganjaran
terbitan gabungan milik berkenaan dengan akal budi sebagai contoh, mempatenkan dan
perizinan) dan komersialisasi. pengamalan milik berkenaan dengan akal budi, hukum dan
peraturan yang mempengaruhi genomic harus bertahan pada asas memaksimalkan pertolongan
umum, tetapi harus juga tetap dengan banyak umum dan longer-established prinsip milik
berkenaan dengan akal budi. lebih jauh, karena genome riset mencakup luas, internasional
treatie, hukum, peraturan, pengamalan, sistem iman dan budaya juga masuk ke dalam arena.
tanpa komersialisasi, paling diagnostik dan kemajuan mengobati akan tidak mencapai klinis
setting, dimana mereka dapat sabar pertolongan. jadi, kami perlu mengembangkan pilihan
kebijakan untuk akses data dan untuk mempatenkan, perizinan dan terbitan milik berkenaan
dengan akal budi lain memudahkan penghamburan genomic data.
puncak halaman <file: /h: \smad-lock\dna\nature01626. html>
ii genomic ke sehat
menterjemahkan genome-based pengetahuan ke keuntungan sehat
peruntunan manusia genome, bersama-sama dengan baru-baru ini lain dan menyangka
pencapaian di genomic, menyediakan peluang tak ada bandingnya ke kemajuan kesepakatan
kami peranan dari faktor genetis di sehat manusia dan penyakit, mengizinkan banyak definisi
akurat non-genetic faktor orang yang bersangkutan, dan menerapkan kepandaian untuk
memahami ini dengan cepat kepada cegahan, diagnosa dan pengurusan penyakit. laporan dengan
kita badan riset nasional itu semula memimpikan hgp dalam nya eksplisit harapan bahwa
manusia genome rangkaian akan mendorong kearah perbaikan di sehat manusia, dan kemudian
rencana lima tahun menegaskan lagi ini view15, <file: /h: \smad-lock\dna\nature01626. html>16,
<file: /h: \smad-lock\dna\nature01626. html>17 <file: /h: \smad-lock\dna\nature01626. html>.
tetapi bagaimana ini akan terjadi telah kurang dengan jelas melafalkan. dengan kelengkapan
tujuan asli hgp, waktunya hak-hak untuk mengembangkan dan terapkan skala luas genomic
strategi menguasakan perbaikan di sehat manusia, sementara mengantisipasi dan menghindari
potensial kesalahan.
demikian strategi harus mengaktifkan komunitas riset mencapai berikut:
· mengenali gen dan trotoar dengan peranan di sehat dan penyakit, dan tentukan bagaimana
mereka saling berhubungan dengan faktor lingkungan.
 · mengembangkan, evaluasi dan terapkan genome-based metode diagnostik untuk ramalan
kepekaan ke penyakit, ramalan tanggapan narkoba, awal pendeteksi keadaan sakit dan klasifikasi
molekuler teliti penyakit.
· mengembangkan dan berbaris metode itu catalyse terjemahan genomic informasi ke
kemajuan mengobati.
tantangan besar ii-1
kembangkan strategi kuat untuk mengenali sumbangan genetis ke penyakit dan tanggapan
narkoba
untuk penyakit biasa, keadaan saling mempengaruhi gen kelipatan dan kelipatan non-genetic
faktor, tak satu pun tunggal allele, biasanya mendikte kepekaan penyakit dan menjawab
pengurusan. membaca dengan susah payah peranan gen di sehat manusia dan penyakit masalah
hebat untuk banyak alasan, termasuk gagap melukiskan secara biologic sah phenotype, tantangan
di mengenali dan mengukur pencahayaan lingkungan, rintangan teknologi ke pembangkitan
cukup dan berguna genotypic informasi, dan berbagai kesulitan belajar manusia. masalah ini
masih dapat memecahkan. pengembangan giat crosscutting genomic alat-alat ke catalyse
kemajuan dalam kesepakatan genetika penyakit biasa dan di pharmacogenomic diperlukan.
menonjol dari antara akan merupakan suatu merinci haplotype dipetakan manusia genome (lihat
tantangan besar i-3 itu dapat menggunakan untuk whole-genome persatuan belajar dari semua
penyakit dalam semua populasi, sebaik lebih jauh kemajuan dalam peruntunan dan genotyping
teknologi membuat demikian belajar layak dikerjakan (lihat 'kuantum melompat', di bawah).
banyak strategi efisien untuk mendeteksi jarang allele orang yang bersangkutan bersama-sama
penyakit juga memerlukan, hipotesa sebagai itu allele resiko menambah itu untuk penyakit biasa
mereka sendiri common30 <file: /h: \smad-lock\dna\nature01626. html> akan mungkin tidak
yang bersifat universal benar. computational dan metode percobaan mengetahui gene-gene dan
gene-environment interaksi, sebaik metode mengizinkan interfacing dari berbagai sesuai basis
data, juga diperlukan (kotak 3 <http: /www. alami.
com/alami/majalah/v422/n6934/kotak/nature01626_bx3. html>. dengan memperoleh penilaian
obyektif resiko penyakit penghubung varian-varian gen teliti itu menyumbang, bujur besar
population-based sepasukan tentara belajar, dengan koleksi informasi klinis luas dan tindak-
lanjut terus menerus, akan sangat kepada berharga belajar dari semua penyakit biasa (kotak 1
<http: /www. alami. com/alami/majalah/v422/n6934/kotak/nature01626_bx1. html>. telah,
demikian proyek sebagai uk biobank (<http: /www. ukbiobank. arus bolak-balik. uk/>,
marshfield clinic' membuat menurut selera proyek riset obat (<http: /www. mfldclin. edu/pmrp>
dan estonian genome proyek (<http: /www. geenivara. ee/> mencarikan menyediakan demikian
sumber daya. tetapi jika kelompok populasi kelipatan di kesatuan negeri dan di tempat lain di
dunia ke pertolongan secara penuh dan agak baik dari demikian riset (lihat tantangan besar ii-6,
besar population-based sepasukan tentara belajar itu termasuk perwakilan penuh populasi
minoritas juga memerlukan.
tantangan besar ii-2
kembangkan strategi mengenali varian-varian gen yang berperan untuk sehat baik dan
pertahanan ke penyakit
paling manusia riset genetis punya secara tradisional memusat di mengenali gen yang
menjadikan cenderung kepada ke keadaan sakit. secara relatif belum diselidiki, tetapi penting,
daerah riset memusat di peranan dari faktor genetis di memelihara sehat baik. genomic akan
memudahkan lebih jauh kesepakatan aspek ini biologi manusia dan bolehkan pengenalan varian-
varian gen itu penting untuk pemeliharaan sehat, terutama di hadapan mengetahui faktor resiko
lingkungan. satu sumber riset berguna akan menjadi suatu 'sepasukan tentara sehat', besar
epidemiologically kelompok kuat individu (kotak 1 <http: /www. alami.
com/alami/majalah/v422/n6934/kotak/nature01626_bx1. html> dengan tidak biasa sehat baik,
siapa dapat membandingkan dengan sepasukan tentara individu dengan penyakit dan siapa dapat
juga secara intensif mempelajari menyatakan allele protektif untuk kondisi seperti kencing
manis, kanker, penyakit jantung dan alzheimer' penyakit. lainnya berjanji mendekati akan ujian
teliti varian-varian genetis di individu resiko tinggi untuk penyakit khusus yang tidak
mengembangkan mereka, seperti dikerjakan sambil duduk, perokok gendut tanpa penyakit
jantung atau individu dengan hnpcc mutasi yang tidak mengembangkan kanker tanda titik dua.
tantangan besar ii-3
kembangkan genome-based mendekati ke ramalan kepekaan penyakit dan tanggapan narkoba,
awal pendeteksi keadaan sakit, dan taksonomi molekuler negeri penyakit
penemuan varian-varian yang mempengaruhi resiko untuk penyakit dapat secara potensial
menggunakan di membedakan dari yang lain obat penangkal - termasuk diet, latihan, lifestyle
dan intervensi obat - memaksimalkan kemungkinan dari tinggal baik. sebagai contoh, penemuan
varian-varian yang berhubungan dengan berhasil hasil terapi narkoba, atau dengan efek samping
malang, dapat secara potensial dengan cepat diterjemahkan ke pengamalan klinis. olakan visi ini
ke kenyataan akan memerlukan berikut: (1 determinasi obyektif resiko berasosiasi dengan
tertentu gen yang lain, sering menaksir terlalu tinggi di awal studies31 <file: /h: \smad-
lock\dna\nature01626. html>; (2 kemajuan teknologi mereduksi ongkos genotyping (kotak 2
<http: /www. alami. com/alami/majalah/v422/n6934/kotak/nature01626_bx2. html>; lihat
'kuantum melompat', di bawah); (3 riset di apakah macam ini membuat menurut selera genomic
informasi akan sebenarnya mengubah sehat kelakuan (lihat tantangan besar ii-5; (4 kekeliruan
implementasi percobaan genetis memastikan bahwa hanya mereka yang mempunyai
mendemonstrasikan keabsahan klinis diterapkan di luar riset setting (kotak 5 <http: /www. alami.
com/alami/majalah/v422/n6934/kotak/nature01626_bx5. html>; dan (5 pendidikan dari
healthcare para profesional dan orang ban untuk;menjadi pengikut berpengetahuan luas di bentuk
baru ini obat penangkal (kotak 6 <http: /www. alami.
com/alami/majalah/v422/n6934/kotak/nature01626_bx6. html>.
waktunya cocok untuk memusat usaha mengerti, dan secara potensial ke reclassify, semua
macam-macam penyakit manusia atas dasar merinci perwatakan molekuler. sistematik meneliti
dari somatic mutasi, epigenetic perubahan, ekspresi gen, protein ekspresi dan protein perubahan
harus mengizinkan definisi taksonomi molekuler baru keadaan sakit, yang akan menggantikan
kita kini, sebagian besar empiris, skema klasifikasi dan kemajuan keduanya cegahan penyakit
dan pengurusan. reclassification dari neuromuscular menyeases32 <file: /h: \smad-
lock\dna\nature01626. html> dan tipe tertentu cancer33 <file: /h: \smad-lock\dna\nature01626.
html> menyediakan menghantam contoh awal, tetapi banyak lagi yang lain demikian aplikasi
mungkin.
taksonomi molekuler seperti itu akan adalah dasar untuk pengembangan lebih baik metode
untuk awal pendeteksi penyakit, yang sering mengizinkan banyak efektif dan kurang pengurusan
mahal sekali. genomic dan skala luas lain mendekati ke biologi tawar potensial untuk
mengembang alat-alat baru mengetahui banyak penyakit lebih segera dari sekarang layak
dikerjakan. demikian 'metode penjaga' boleh termasuk analisis ekspresi gen di berputar-putar
leukocyte, proteomic analisis tubuh cair, dan lanjutan analisis molekuler tisu biopsie. contoh
akan adalah analisis ekspresi gen di darah sekeliling leukocyte meramalkan tanggapan narkoba.
memusat usaha menggunakan genomic mendekati menggambarkan serum protein secara
mendalam di sehat dan penyakit boleh juga sangat memberi penghargaan.
tantangan besar ii-4
gunakan kesepakatan baru gen dan trotoar mengembangkan mengobati baru bertenaga
mendekati ke penyakit
obat di sasaran pasar lebih sedikit daripada 500 gen manusia products34 <file: /h: \smad-
lock\dna\nature01626. html>. suingguhpun tidak semua 30,000 atau manusia protein-coding
genes<file: /h: \smad-lock\dna\nature01626. html> akan punya produk targetable untuk
pengembangan narkoba, ini menyatakan bahwa ada kubangan belum digunakan hebat manusia
gene-based sasaran-sasaran untuk intervensi mengobati. sebagai tambahan, kesepakatan baru
trotoar biologis menyediakan oleh genomic (lihat tantangan besar i-2 harus menyumbang lebih
lagi pada dasarnya ke desain mengobati.
informasi memerlukan menentukan potensial mengobati dari gen biasanya tumpang tindih
dengan berat dengan informasi yang menyatakan fungsi nya. sukses imatinib mesylate (gleevec,
penghambat bcr-abl tyrosine kinase, di traktiran kronis myelogenou leukaemia bersandar pada
merinci kesepakatan molekuler disease' genetis cause35 <file: /h: \smad-lock\dna\nature01626.
html>. contoh ini menawarkan memberi harapan itu therapie berdasarkan di genomic informasi
akan [jadi] terutama efektif. tantangan besar i-1 menjelaskan 'functionation genome, yang akan
makin bertambah kritis pertama masuk pengembangan mengobati baru. tetapi rangsang ilmuwan
dasar mendekati biomedical masalah dengan genomic sikap tidak cukup. mengobati mindset,
kekurangan banyak pelajar biomedical riset dan latihan, harus dengan tegas mendorong, dan
alat-alat membangun dan memperlengkapi implementasi nya.
terutama berjanji contoh gene-based mendekati ke mengobati aplikasi 'kimia genomics'25
<file: /h: \smad-lock\dna\nature01626. html>. siasat ini menggunakan perpustakaan molekul
kecil (daerah bertembok alami, aptamer atau produk combinatorial kimia) dan high-throughput
saringan ke kesepakatan kemajuan trotoar biologis dan mengenali daerah bertembok yang
sebagai positif atau pengatur negatif produk gen sendiri, trotoar atau seluller phenotype.
meskipun industri obat menerapkan ini mendekati meluas sebagai pertama masuk pengembangan
narkoba, beberapa pemeriksa pelajar punya akses pada ini metodologi atau terbiasa dengan
penggunaannya.
membuktikan demikian akses banyak dengan luas, melalui satu atau banyak memusatkan
fasilitas, dapat mendorong kearah penemuan berguna sejumlah besar menyelidiki untuk trotoar
biologis itu akan bertindak sebagai bahan reaksi baru untuk riset dasar dan/atau titik awal untuk
pengembangan agen mengobati baru ( 'mengenai' dari demikian layar perpustakaan akan
biasanya memerlukan kimia berkenaan dengan obat perubahan ke hasil therapeutically daerah
bertembok dapat dipakai).
juga memerlukan baru, banyak teknologi bertenaga untuk perpustakaan molekuler dalam
pembangkitan, khususnya orang-orang memasang label mengizinkan determinasi uang kontan
sasaran-sasaran molekuler akurat. memusatkan basis data hasil saringan harus mendorong kearah
lebih jauh kepandaian untuk memahami biologis penting. molekuler pembangkitan menyelidiki
untuk menyelidiki biologi dasar sehat dan penyakit di laboran pelajar akan tidak menggantikan
utama peranan dari biopharmaceutical perusahaan-perusahaan di pengembangan narkoba, tetapi
dapat berperan untuk mulai alur pipa pengembangan narkoba. sektor swasta akan yakin
menemukan banyak dari molekuler ini menyelidiki minat untuk lebih jauh eksplorasi melalui
optimisasi dengan kimia berkenaan dengan obat, pengesahan sasaran, pimpin pengenalan daerah
bertembok, toxicological belajar dan, akhirnya, percobaan klinis.
 pelajar pengejaran dari ini pertama masuk pengembangan narkoba dapat terutama berharga
untuk banyak jarang mendelian penyakit, di mana sering cacat gen dikenal tetapi keterbatasan
ukuran pasar kecil pribadi sector' motivasi ke terang-terangan biaya pengembangan obat efektif.
demikian translational riset di laboran pelajar, menggabungkan dengan perangsang seperti kita
narkoba yatim bertindak, dapat sangat menambah ketersediaan pengurusan efektif untuk
penyakit genetis jarang di berikut dasawarsa. lebih jauh, pengembangan mengobati mendekati ke
single-gene kekalutan boleh menyediakan kepandaian untuk memahami berharga ke menerapkan
genomic menyatakan biologi banyak kekalutan biasa dan mengembang banyak pengurusan
efektif untuk mereka (di jalan itu, sebagai contoh, mencari-cari daerah bertembok sasaran itu
presenilin telah memimpin ke umum strategi mengobati untuk late-onset alzheimer' menyease36
<file: /h: \smad-lock\dna\nature01626. html>.
tantangan besar ii-5
periksa bagaimana informasi resiko genetis menyampaikan di klinis penyesuaian, bagaimana
informasi itu mempengaruhi strategi sehat dan kelakuan, dan bagaimana ini mempengaruhi hasil
sehat dan berharga
kesepakatan bagaimana faktor genetis mempengaruhi sehat sering mengutip sebagai gol
utama genomic, di anggapan yang menerapkan demikian kesepakatan di klinis setting akan
meningkatkan sehat. tetapi anggapan ini sebenarnya mempercayai pada; bersandarkan secara
relatif beberapa contoh dan data, dan banyak riset diperlukan menyediakan cukup pedoman
tentang bagaimana cara menggunakan genomic informasi optimally untuk memperbaiki sendiri
atau kesehatan masyarakat.
secara teoritis, langkah dengan mana informasi resiko genetis akan mendorong kearah
memperbaiki sehat: (1 perorangan memperoleh genome-based informasi tentang resiko sehat
sendiri dia/dia; (2 sendiri menggunakan informasi ini mengembangkan membedakan dari yang
lain cegahan atau rencana pengurusan; (3 sendiri melengkapkan rencana itu; (4 ini memimpin ke
arah memperbaiki sehat; dan (5 healthcare berharga direduksi. pengamatan anggapan ini
diperlukan, keduanya ke percobaan mereka dan menentukan bagaimana setiap langkah dapat
terbaik ulung di berbeda klinis penyesuaian.
riset juga diperlukan itu dengan kritis menilai percobaan genetis baru dan intervensi
parameter dalam kaitan dengan seperti keuntungan, akses dan berharga. demikian riset harus
interdisciplinary dan gunakan alat-alat dan keahlian ladang, termasuk genomic, sehat pendidikan,
sehat riset kelakuan, riset hasil sehat, healthcare analisis pengiriman, dan healthcare ekonomi.
sebagian dari ladang ini punya secara historis membayar perhatian kecil ke genomic, tetapi
high-quality riset jenis ini dapat menyediakan pedoman penting di pengambilan keputusan klinis
- sebagai bekerja dari beberapa gemblengan punya telah suka menolong di mengawasi orang
dengan meningkat resiko kanker tanda titik dua sebagai hasil mutasi di fap atau hnpcc 37
<file: /h: \smad-lock\dna\nature01626. html>.
tantangan besar ii-6
kembangkan genome-based alat-alat yang meningkatkan sehat
disparitie di sehat peraturan keadaan signifikan mencakup luas memberitakan, tetapi dapat
genome-based mendekati ke sehat dan penyakit membantu ke arah mereduksi masalah ini? sosial
dan faktor lingkungan lain penyumbang utama ke sehat disparitie; tentu saja, akan pertanyaan
apakah faktor turun temurun mempunyai signifikan peranan. tetapi perbedaan populasi di allele
frekuensi untuk menyease-associated varian-varian dapat menyokong faktor ke tertentu disparitie
di sehat keadaan, menemani informasi ini ke penangkal dan/atau public-health strategi akan
berguna. riset diperlukan mengerti hubungan diantara genomic dan sehat disparitie dengan
dengan kaku mengevaluasi bermacam-macam sumbangan keadaan ekonomi-sosial, budaya,
diskriminasi, sehat kelakuan, diet, pencahayaan lingkungan dan genetika.
ini juga penting menjelajahi aplikasi genomic di perbaikan sehat di mengembang dunia
(<http: /www3. siapa. int/whosi/genomic/genomics_report. cfm>, dimana keduanya manusia dan
non-human genomic akan bermain signifikan peranan. jika kita mengambil malaria sebagai suatu
contoh, lebih baik kesepakatan manusia faktor genetis yang mempengaruhi kepekaan dan
menjawab penyakit, dan kepada narkoba menggunakan mentraktir ini, dapat punya signifikan
tubrukan mencakup luas. terlalu dapat lebih baik kesepakatan benalu berkenaan dengan malaria
sendiri dan tentang nya vektor nyamuk, yang mana melaporkan genome sequences38 baru-baru
ini, <file: /h: \smad-lock\dna\nature01626. html>39 <file: /h: \smad-lock\dna\nature01626. html>
harus menyediakan. ini akan [jadi] perlu menentukan peranan tepat bidang pemerintah dan
organisasi non pemerintah, lembaga pelajar, industri dan individu memastikan bahwa genomic
memproduksi keuntungan klinis untuk resource-poor bangsa, dan digunakan memproduksi kuat
lokal keahlian riset.
memastikan bahwa genomic keuntungan riset semua, ini akan [jadi] kritis menguji bagaimana
genomics-based pelayanan kesehatan mengakses dan menggunakan. apakah [yang merupakan]
penghalang ke akses pantas, dan bagaimana mungkin mereka memindahkan? ini adalah sesuai
tidak hanya di resource-poor bangsa, tetapi juga di negara lebih kaya dimana bagian masyarakat,
seperti populasi asli, tak diasuransikan, atau pedesaan dan komunitas bagian tertua suatu kota,
punya secara tradisional tidak menerima cukup pelayanan kesehatan.
puncak halaman <file: /h: \smad-lock\dna\nature01626. html>
iii genomic ke masyarakat
mempromosikan menggunakan dari genomic memaksimalkan keuntungan dan kecilkan
rugikan
genomic telah di bagian terdepan dari memberikan perhatian serius, melalui riset sangat
terpelajar dan bahasan kebijaksanaan, kepada tubrukan ilmu pengetahuan dan teknologi di
masyarakat. meskipun keuntungan utama untuk;menjadi mewujudkan dari genomic di area sehat,
sebagai menjelaskan di atas, genomic dapat juga berperan untuk segi lain masyarakat. sama
[halnya] hgp dan dihubungkan pembangunan telah menelurkan wilayah baru riset di biologi
dasar dan di sehat, mereka telah juga menciptakan kesempatan untuk riset di terbitan sosial,
bahkan untuk sejumlah kesepakatan banyak secara penuh bagaimana kami mengartikan diri kita
dan saling.
di berikut sedikit tahun, masyarakat harus tidak hanya melanjutkan bergulat dengan
pertanyaan banyak mengangkat oleh genomic, tetapi harus juga jabarkan dan kebijaksanaan
perkakas ke alamat banyak di antara mereka. kalau riset menyediakan data andal dan teliti
mendekati yang di atasnya ke markas demikian keputusan, kebijaksanaan itu akan [jadi] ill-
informed dan dapat secara potensial penyelesaian perselisihan kita semua. agar berhasil, riset ini
harus meliputi keduanya 'pemeriksaan dasar' yang mengembangkan alat-alat konseptual dan
dibagi vocabularie, dan banyak 'menerapkan', 'translational proyek yang menggunakan alat-alat
ini menjelajahi dan definisikan tepat public-policy itu pilihan mempersatukan bermacam-macam
titik melihat.
sebagai ini telah di masa lalu, demikian riset akan melanjutkan punya jaringan penting untuk
semua tiga tema utama visi menyajikan disini. kami sekarang riset alamat yang memusat di
masyarakat sendiri, lebih dari di biologi atau sehat. demikian usaha harus mengaktifkan
komunitas riset ke:
 · meneliti tubrukan genomic di konsep ras, ethnicity, kekeluargaan, sendiri dan grup identitas,
sehat, penyakit dan 'kewajaran' untuk ciri dan kelakuan.
· mengartikan pilihan kebijakan, dan akibat potensial mereka, untuk menggunakan dari
genomic informasi dan untuk batas etis mengelilingi genomic riset.
tantangan besar iii-1
kembangkan pilihan kebijakan untuk menggunakan dari genomic di medis dan non-medical
penyesuaian
survei punya berkali-kali menunjukkan bahwa umum sangat tertarik akan konsep pribadi itu
informasi genetis boleh penunjuk jalan mereka ke lebih baik sehat, tetapi mendalam mengenai
tentang potensial menyalahgunakan menyangkut itu informasi (lihat <http: /www. publicagenda.
org/terbitan/pcc_detail. cfm? issue_type=medical_research&list=7>. bagus sekali daftar
mengenai potensial untuk diskriminasi di asuransi kesehatan dan tenaga kerja. signifikan jumlah
riset di ini memberitakan telah done40 <file: /h: \smad-lock\dna\nature01626. html>, pilihan
kebijakan telah published41, <file: /h: \smad-lock\dna\nature01626. html>42, <file: /h: \smad-
lock\dna\nature01626. html>43 <file: /h: \smad-lock\dna\nature01626. html>, dan banyak kita
negeri punya sekarang melewati anti-discrimination perundang-undangan (lihat <http: /www.
genome. gov/halaman/policyethic/sudah tidak berguna lagi/stateins> dan <http: /www. genome.
gov/halaman/policyethic/sudah tidak berguna lagi/stateemploy>. kita sama tenaga kerja komisi
peluang telah memerintah bahwa amerika dengan disabilitie bertindak harus berlaku bagi
diskriminasi berdasarkan di genetis bersifat prediksi information44 <file: /h: \smad-
lock\dna\nature01626. html>, tetapi kedudukan hukum membangun sisa dalam beberapa
meragukan. meskipun pelaksana pesanan melindungi kita pemerintah karyawan melawan
diskriminasi genetis, ini tidak berlalu bagi pekerja lain. jadi, banyak pengamat telah
menyimpulkan perundang-undangan federal efektif itu diperlukan, dan kita kongres sekarang
hukum seperti itu mempertimbangkan.
memastikan percobaan genetis itu menawarkan kepada telah mendirikan keabsahan umum
klinis dan kegunaan harus prioritas untuk masa depan riset dan kebijaksanaan membuat. di
kesatuan negeri, secretary' panitia berhak memberi nasehat di ujian genetis secara luas meninjau
kembali daerah ini dan menyimpulkan itu lebih jauh kekeliruan diperlukan, menanyakan
makanan dan tata usaha narkoba meninjau percobaan genetis bersifat prediksi baru sebelum
pemasaran (<http: /www4. od. nih. gov/oba/sacgt/laporan/oversight_report. pdf>. rekomendasi
itu tidak masih bertindak di; sementara itu, banyak website menawarkan unvalidated percobaan
genetis secara langsung kepada umum, sering menggabungkan dengan penjualan 'nutraceutical
dan produk lain sangat nilai diragukan, berkembang biak.
banyak terbitan sekarang pusaran mengelilingi besar mengantar dari riset genetis menyertakan
pokok manusia, dan lebih jauh bekerja diperlukan mencapai memuaskan seimbang diantara
proteksi pengikut riset dari kesalahan dan kemampuan mengantar riset klinis masyarakat
keuntungan itu secara keseluruhan. banyak usaha telah masuk mengembang petunjuk tepat untuk
menggunakan dari tersedia contoh tisu (<http: /www. georgetown. edu/riset/nrcbl/nbac/hbm.
pdf>, untuk konsultasi komunitas bila melaksanakan riset genetis dengan populasi bisa
diidentifikasi (http: /www. nigm. nih. gov/berita/laporan/community_consultation. html#exec
<http: /www. nigm. nih. gov/berita/laporan/community_consultation. html>, dan untuk
mengabulkan dari non-examined para anggota keluarga bila melaksanakan riset asal-usul
(<http: /www. nih. gov/sig/bioethic/nih_third_party_rec. html>, tetapi kekacauan masih sisa
untuk banyak pemeriksa dan kelembagaan meninjau papan.
 menggunakan dari genomic informasi tidak membatasi pada gelanggang biologi dan sehat,
dan lebih jauh riset dan pengembangan kebijakan pilihan juga memerlukan untuk banyak
aplikasi lain demikian informasi. mempersiapkan dari pengguna tambahan mungkin termasuk
hidup, cacat dan jangka panjang merawat industri asuransi, sistem sah, militer, lembaga
pendidikan dan perwakilan adopsi. walaupun beberapa riset memberi tahu medis menggunakan
dari genomic akan [jadi] berguna di lebih luas penyesuaian, mempersembahkan di luar itu riset
healthcare kegiatan diperlukan menjelajahi orang ban nilai yang berlaku bagi menggunakan dari
genomic selain dari untuk pelayanan kesehatan dan mereka hubungan ke khusus aplikasi
kontekstual. sebagai contoh, harus informasi genetis di kecenderungan hyperactivity tersedia di
masa datang ke sekolah resmi? atau harus informasi genetis tentang ciri perilaku dapat
dipertimbangkan di kriminal atau cara bekerja sipil? genomic juga menyediakan lebih besar
peluang mengerti asal nenek moyang populasi dan individu, yang ajukan terbitan seperti apakah
informasi genetis harus menggunakan untuk melukiskan keanggotaan di grup minoritas.
karena menggunakan dari genomic di luar itu healthcare setting akan meliputi dengan mantap
komunitas lebih luas pemegang taruhan, keduanya riset dan pengembangan kebijaksanaan di
daerah ini harus meliputi individu dan organisasi lagipula itu orang yang bersangkutan di
aplikasi medis genomic. tetapi banyak dari sama visi pokok ke riset dan pengembangan
kebijaksanaan untuk medis menggunakan dari genomic juga pokok. keduanya pengguna
potensial non-medical aplikasi genomic dan orang ban perlu pendidikan mengerti lebih baik
alami dan keterbatasan genomic informasi (kotak 6 <http: /www. alami.
com/alami/majalah/v422/n6934/kotak/nature01626_bx6. html> dan mengerti etis, sah dan
implikasi sosial menggunakan pelayanan kesehatan bagian luar (kotak 5 <http: /www. alami.
com/alami/majalah/v422/n6934/kotak/nature01626_bx5. html>.
tantangan besar iii-2
pahami hubungan diantara genomic, ras dan ethnicity, dan akibat membongkar hubungan ini
ras sebagian besar non-biological konsep memalukan oleh salah faham dan sejarah panjang
prasangka. hubungan dari genomic kepada konsep ras dan ethnicity harus dianggap dalam
historis gabungan dan perhubungan sosial.
paling variasi di genome dibagi diantara semua populasi, tetapi tertentu allele banyak sering
dalam beberapa populasi daripada di pihak lain, sebagian besar sebagai hasil sejarah dan
geografi. gunakan dari data genetis mengartikan kelompok rasial, atau dari rasial categorie
menggolongkan ciri biologis, cenderung akan kesalahan menafsir. mengurangi demikian
kesalahan menafsir, biologis dan sociocultural faktor yang menghubungkan satu dng lain
genetika dengan membangun ras dan ethnicity perlu untuk;menjadi lebih baik mengerti dan
berkomunikasi dalam berikut sedikit tahun.
ini akan memerlukan riset di bagaimana berbeda individu dan hamil budaya ras, ethnicity,
grup identitas dan self-identity, dan apa peranan mereka percaya gen atau faktor biologis lain
punya. ini akan juga memerlukan pemeriksaan kritis dari bagaimana komunitas ilmiah mengerti
dan menggunakan konsep ini di penuh tipu daya riset dan menyajikan menemukan, dan dari
bagaimana laporan media ini. juga perlu tersebar tentang pendidikan arti biologis dan
pembatasan riset menemukan di (kotak daerah ini 6 <http: /www. alami.
com/alami/majalah/v422/n6934/kotak/nature01626_bx6. html>, dan formulasi dan adopsi
public-policy itu pilihan melindungi dari genomics-based diskriminasi atau penganiayaan (lihat
tantangan besar iii-1.
tantangan besar iii-3
pahami akibat membongkar genomic sumbangan ke ciri manusia dan kelakuan
 gen mempengaruhi tidak hanya sehat dan penyakit, tetapi juga ciri manusia dan kelakuan.
ilmu pengetahuan baru permulaan ke lepas trotoar rumit yang mendasari demikian sifat sebagai
ulinan, pengamatan, irama harian dan macam karakteristik perilaku. terlalu sering, riset di
genetika perilaku, seperti itu bertalian dengan orientasi seksual atau kecerdasan, telah dirancang
kurang baik dan temuan nya telah berkomunikasi dengan cara yang oversimplifie dan lebih-
lebihkan peranan dari faktor genetis. telah disebabkan masalah ini serius untuk yang yang telah
menggambarkan dengan sinis oleh saran itu allele berasosiasi dengan apa [yang] sebagian orang
melihat sebagai fisiologis negatif' atau ciri perilaku banyak sering di populasi tertentu. dengan
sejarah dan nyata potensial untuk pengulangan, ini terutama penting mengumpulkan cukup
secara ilmiah informasi sah tentang genetis dan faktor lingkungan menyediakan kesepakatan
suara sumbangan dan interaksi diantara gen dan lingkungan di gabungan ini phenotype.
ini juga penting bahwa di sana riset kuat menyelidiki implikasi, untuk keduanya individu dan
masyarakat, dari membongkar beberapa genomic sumbangan itu mungkin ada ke ciri dan
kelakuan. ladang genomic punya tanggungjawab menganggap implikasi sosial me-riset
sumbangan genetis ke ciri dan kelakuan, barangkali bahkan tanggung jawab lebih besar daripada
di wilayah lain dimana ada kurang dari sejarah salah faham dan stigmatization. keputusan
tentang riset di daerah ini sering membuat dengan masukan dari bermacam-macam kelompok
individu terbaik dan organisasi.
tantangan besar iii-4
menaksir bagaimana cara mengartikan batas etis untuk menggunakan dari genomic
genetika dan genomic dapat menyumbang kesepakatan ke banyak wilayah biologi, sehat dan
hidup. sebagian dari aplikasi manusia ini kontroversial, dengan para anggota orang ban menanyai
wajar dari eksplorasi ilmiah mereka. meskipun kebebasan untuk permintaan keterangan ilmiah
telah keistimewaan mata angin utama manusia kemajuan, ini tidak tak terhingga. adalah penting
bagi masyarakat mengartikan tepat dan tidak sesuai menggunakan dari genomic. percakapan
diantara bermacam-macam perjanjian berdasarkan di teliti dan merinci kesepakatan sesuai ilmu
pengetahuan dan etis, sah dan faktor sosial akan memajukan formulasi dan implementasi
kebijaksanaan efektif. sebagai contoh, di ujian genetis reproduktif, ini penting sekali termasuk
visi dari komunitas cacat. riset harus menjelajahi bagaimana berbeda individu, budaya dan tradisi
agama melihat batas etis untuk menggunakan dari genomic - sebagai contoh, yang satuan nilai
menentukan sikap ke arah kepantasan menerapkan genomic ke demikian wilayah sebagai ujian
genetis reproduktif, 'peningkatan genetis' dan germline gen mengirimkan.
puncak halaman <file: /h: \smad-lock\dna\nature01626. html>
implementasi: nhgri' peranan
visi untuk masa depan dari genomic menyajikan disini luas dan dalam, dan pelaksanaan nya
akan memerlukan usaha. lanjutan kerja sama luas diantara ilmuwan dan diantara sumber
pembiayaan yang menggolongkan hgp akan [jadi] pokok. meskipun nhgri bermaksud mengikuti
di semua wilayah riset membahas disini, ini akan perlu ke fokus usaha nya menggunakan sumber
daya terbatas nya sebagai secara efektif sebagai mungkin. jadi, ini akan mengambil utama
peranan dalam beberapa wilayah, sangat rajin bekerja sama di pihak lain, dan punya hanya
mendukung peranan di masih lain. nhgri' prioritie dan wilayah penekanan akan juga menyusun
sebagai penunjuk jarak dalam mil ditemui dan baru kesempatan timbul.
mendekati telah menggolongkan genomic itu dan men sukses hgp - fokus awal di
pengembangan teknologi dan feasibility belajar, diikuti oleh usaha penerbang mempelajari
bagaimana cara menerapkan strategi baru dan teknologi secara efisien di lebih besar skala, dan
kemudian implementasi full-scale usaha produksi - akan melanjutkan untuk;menjadi berada di
pusat nhgri' priority-setting proses. berikut wilayah minat tinggi, tidak terdaftar di prioritas
pesanan.
produksi skala luas genomic kumpulan data
nhgri akan melanjutkan ke dukungan genomic peruntunan, memusatkan di genome mamalia,
hewan bertulang belakang, chordate dan hewan tak bertulang punggung; lain funder akan
dukungan determinasi tambahan genome rangkaian dari kuman dan tanam-tanaman. dengan
teknologi arus, nhgri dapat dukungan determinasi sebanyak 45-60 gigabase dari genomic dna
rangkaian, atau yang sejenisnya 15-20 manusia genome, dalam yang akan datang lima tahun.
tetapi ongkos sebagai peruntunan melanjutkan ke lorot, rasio berharga/pertolongan generasi
rangkaian akan meningkatkan, sehingga jumlah yang sebenarnya peruntunan berbuat akan [jadi]
sangat mempengaruhi oleh pengembangan memperbaiki teknologi peruntunan.
keputusan tentang yang genome ke rangkaian berikut akan [jadi] berdasarkan di hasil
berdasarkan perbandingan meneliti itu menyatakan kemampuan genomic rangkaian dari belum
diselidiki phylogenetic posisi memberitahu tafsiran rangkaian manusia dan menyediakan
kepandaian untuk memahami lain. akhirnya, derajat yang beberapa baru genomic rangkaian
disempurnakan - selesai, mengambil ke lanjutan tingkatan naskah atau enteng sampled - akan
[jadi] bertekad dengan menggunakan di mana rangkaian dibangitkan. dan, , nhgri' program
peruntunan akan mengendalikan menutup hubungan dengan, dan memperhatikan rencana dan
hasil, program peruntunan lain, sebagai telah terjadi sepanjang hgp.
siap seperangkat data kedua untuk production-level usaha manusia haplotype dipetakan
(hapmap. proyek ini, kerja sama diantara nhgri, banyak lain nih institut, dan empat pasangan
internasional, dijadwalkan untuk kelengkapan dalam tiga tahun. hasil internasional hapmap
proyek akan dengan mantap bentuk masa depan petunjuk nhgri' usaha riset di area variasi
genetis.
pilot-scale usaha
nhgri telah memulai menyandikan proyek mulai pengembangan manusia genome 'daftar
bagian'. pertama gelombang akan alamat aplikasi dan perbaikan ada teknologi untuk pengenalan
skala luas rangkaian persandian, satuan rekaman dan unsur fungsional lain di mana teknologi
sekarang tersedia. bila hasil menyandikan proyek menunjukkan tanda-tanda dari kemanjuran dan
afordabilitas di skala penerbang, ganjaran akan [jadi] memberi menerapkan teknologi tepat
melintasi seluruh manusia genome.
pengembangan teknologi
banyak wilayah kritis kepentingan kepada pelaksanaan genomics-based visi untuk biomedical
riset memerlukan teknologi baru dan pembangunan metodologis sebelum penerbang dan
kemudian skala luas mendekati dapat berusaha. mengenali pengembangan teknologi itu mahal
dan high-risk pekerjaan, nhgri meskipun demikian merasa terikat dengan mendukung dan
mengembangkan pengembangan teknologi di banyak dari wilayah penting sekali ini, termasuk
berikut.
dna peruntunan. ada masih peluang besar mereduksi berharga dan menambah throughput dari
dna peruntunan, dan membuat cepat, peruntunan murah tersedia banyak dengan luas. penurunan
radikal peruntunan berharga akan mendorong kearah sangat berbeda mendekati ke biomedical
riset.
 variasi genetis. memperbaiki genotyping metode dan lebih baik metode matematis perlu
membuat efektif menggunakan informasi tentang struktur variasi di manusia genome untuk
mengenali sumbangan genetis ke penyakit manusia dan ciri gabungan lain.
genome 'daftar bagian'. rangkaian persandian di seberang dan transcriptional satuan, baru
computational dan percobaan mendekati diperlukan mengizinkan determinasi lengkap sequence-
encoded unsur fungsional di genome.
proteomic. dalam jangka pendek, nhgri mengharapkan ke fokus di pengembangan tepat,
scalable teknologi untuk analisa menyeluruh dari protein dan protein mesin di sehat manusia dan
di keduanya jarang dan penyakit gabungan.
trotoar dan jaringan. sebagai pelengkap kepada pengembangan genome 'daftar bagian' dan
makin bertambah efektif mendekati ke proteome analisis, nhgri akan menganjurkan
pengembangan teknologi baru yang mengadakan buatan melihat dari jaringan pengaturan genetis
dan saling berinteraksi protein trotoar.
sumbangan genetis ke sehat, penyakit dan tanggapan narkoba. nhgri akan tempat prioritas
tinggi di membuat dan menerapkan baru crosscutting genomic alat-alat, teknologi dan strategi
memerlukan mengenali basis genetis secara medis sesuai phenotype. riset di sumbangan genetis
ke jarang dan penyakit biasa, dan ke tanggapan narkoba, akan khas meliputi sistem biologis dan
penyakit minat utama ke lain nih institut dan organisasi pembiayaan lain. oleh sebab itu, nhgri
mengharapkan bahwa keterlibatan nya di daerah ini riset akan sering melaksanakan melalui
persekutuan dan kerja sama. nhgri terutama tertarik akan riset rangsang mendekati kepada
pengenalan varian-varian gen yang menganugerahkan penyakit pertahanan dan penjelmaan lain
'sehat baik'.
molekuler menyelidiki, termasuk molekul kecil dan rna-mediated campur tangan, untuk
menyelidiki biologi dasar dan penyakit. eksplorasi feasibility dari kimia berkembang genomic di
pelajar dan sektor umum, terutama mengenai pendirian satu atau banyak memusatkan fasilitas,
akan [jadi] mengejar oleh nhgri di rekanan dengan lain.
basis data
lainnya jenis sumber komunitas untuk biologis dan biomedical komunitas riset
direpresentasikan oleh basis data (kotak 3 <http: /www. alami.
com/alami/majalah/v422/n6934/kotak/nature01626_bx3. html>. tetapi dukungan mereka
mewakili secara potensial signifikan masalah. perwakilan pembiayaan, mencerminkan minat
komunitas riset, tegangkan lebih suka menggunakan dana riset mereka ke dukungan data baru
pembuatan, dan terus menerus perlu untuk melanjutkan dan meningkat dukungan untuk arsip
data dan akses kuat ke mereka sering memberi kurang perhatian. keduanya komunitas ilmiah dan
perwakilan pembiayaan harus mengakui investasi itu di kreasi dan pemeliharaan basis data
efektif sebagai penting menjadikan lengkap pembiayaan riset sebagai generasi data. nhgri telah
sumber utama dukungan untuk beberapa utama genetika/genomics-oriented basis data, termasuk
tikus genome basis data (<http: /www. informatic. jax. org/mgihome/mgd/aboutmgd. shtml>,
saccharomyce genome basis data (<http: /genome-www. stanford. edu/saccharomyces>, flybase
(<http: /flybase. bio. indiana. edu/>, wormbase (<http: /www. wormbase. org/> dan online
mendelian warisan di pria (<http: /www. ncbi. nlm. nih. gov/omim>. nhgri akan melanjutkan
untuk menjadi pemimpin di menyelidiki enceran efektif kepada terbitan menggabungkan,
menampilkan dan membuktikan akses ke genomic informasi.
etis, sah dan riset sosial
nhgri' elsi aktifitas riset akan makin bertambah fokus di asasi, meluas sesuai, terbitan
bermasyarakat. komunitas sarjana dan peneliti bekerja di ladang sosial ini, sebaik lingkungan
terbitan sedang menyelidiki, perlukan untuk;menjadi memperluas. elsi komunitas riset harus
termasuk individu dari minoritas dan komunitas lain yang mungkin tak sebanding mempengaruhi
oleh menggunakan atau salahgunakan dari informasi genetis. mekanisme baru untuk
mempromosikan mengalogue dan kerja sama diantara elsi peneliti dan genomic dan peneliti
klinis perlu untuk;menjadi membangun; demikian contoh boleh termasuk membangun hadiah
untuk interdisciplinary riset, kursus musim panas intensif atau mini-fellowship untuk cross-
training, dan kreasi pusat keunggulan di elsi belajar mengizinkan diteruskan interdisciplinary
kerja sama.
populasi bujur cohort(
ini berjanji sumber riset akan [jadi] dengan luas dapat dipakai, dan akan butuhkan demikian
pembiayaan luas itu, meskipun nhgri boleh punya mendukung peranan di desain dan kekeliruan,
sukses akan permintaan keterlibatan dan dukungan sumber pembiayaan lain.
non-genetic faktor di sehat dan penyakit
akibat memperbaiki definisi faktor genetis mendasari sehat manusia dan penyakit akan
merupakan suatu perbaikan di pengakuan dan definisi lingkungan dan lain non-genetic
sumbangan ke ciri itu. ini adalah lainnya daerah di mana nhgri akan [jadi] orang yang
bersangkutan melalui pengembangan strategi baru dan dengan membentuk persekutuan.
gunakan dari genomic informasi meningkatkan pelayanan kesehatan
nhgri akan catalyse kerja sama diantara bermacam-macam gemblengan sangat terpelajar siapa
punya usaha hubungan akan [jadi] yang penting bagi riset di jalan terbaik untuk sabar dan
healthcare provider membuat efektif menggunakan dari membuat menurut selera informasi
genetis di perbaikan sehat. nhgri akan juga berusaha memastikan bahwa riset di daerah ini
diinformasikan oleh, dan memperluas pengetahuan, implikasi bermasyarakat genomic.
memperbaiki sehat orang
ini akan [jadi] penting untuk nhgri ke riset dukungan yang menjelajahi bagaimana cara
memastikan bahwa genomic informasi digunakan, kepada tingkat itu demikian informasi sesuai,
mereduksi sehat mencakup luas disparitie. itu akan termasuk usaha giat ke menambah
perwakilan minoritas di barisan genomic peneliti. tetapi enceran penuh sehat disparitie masalah
dapat hanya terjadi melalui suatu melakukan dan diteruskan usaha dengan pemerintahan, sistem
medis dan masyarakat.
pengembangan kebijaksanaan
nhgri akan melanjutkan membantu memudahkan public-policy pengembangan di area
genetis/genomic ilmu pengetahuan. pengembangan kebijaksanaan efektif akan memerlukan
perhatian ke terbitan itu di mana ini dapat punya tubrukan terbesar di agenda kebijaksanaan dan
dapat membantu ke arah memudahkan genomic ilmu pengetahuan. nhgri akan juga fokus di
terbitan itu akan membantu orang ban di menguntungkan dari genomic, seperti keleluasaan
pribadi informasi genetis, akses ke pelayanan-pelayanan genetika, pemasaran merect-to-
consumer/provider, mempatenkan dan perizinan informasi genetis, pengurusan tepat pengikut
manusia di riset, dan standard, kegunaan dan kualitas di ujian genetis.
puncak halaman <file: /h: \smad-lock\dna\nature01626. html>
data mengeluarkan
pelajaran penting hgp telah pertolongan segera melepaskan data dari proyek peruntunan skala
luas, sebagai mewujudkan di bermuda prinsip (<http: /www. gen. ucl. arus bolak-balik.
uk/hugo/bermuda. htm>. beberapa lain proyek produksi data skala luas telah mengikuti warna
seperti itu untuk full-length cdna dan single-nucleotide polymorphism, kepada pertolongan
komunitas ilmiah. ilmiah kemajuan dan pertolongan umum akan [jadi] memaksimalkan oleh
awal, buka dan melanjutkan akses ke kumpulan data besar dan dengan memastikan bahwa
ilmuwan baik sekali kepincut kepada tugas menghasilkan banyak sumber daya jenis ini. untuk
sistem ini melanjutkan bekerja, produsen community-resource kumpulan data punya perjanjian
membuat hasil usaha mereka dengan cepat tersedia untuk gratis dan leluasa menggunakan oleh
komunitas ilmiah, dan pengguna sumber punya perjanjian mengakui dan kehormatan
sumbangan penting membuat oleh ilmuwan yang menyumbang mereka waktu dan usaha ke
produksi sumber.
meskipun prinsip ini telah biasanya mewujudkan di kotak genomic dna peruntunan, mereka
tidak untuk banyak tipe lain community-resource proyek (membangun koordinat biologi atau
data ekspresi gen, untuk contoh). pengembangan sistem efektif untuk mencapai cepat
mengeluarkan data tanpa pembatasan dan untuk membuktikan melanjutkan tersebar akses ke
material dan alat-alat riset harus menjadikan lengkap integral perencanaan dan pengembangan
sumber daya komunitas baru. komunitas ilmiah harus juga mengembangkan perangsang ke
dukungan sukarela mengeluarkan dari demikian data sebelum penerbitan dengan pemeriksa
sendiri, dengan sewajarnya memberi penghargaan dan melindungi minat ilmuwan yang harapan
ke data mereka berbagi dengan komunitas dalam yang sedemikian cara dermawan.
puncak halaman <file: /h: \smad-lock\dna\nature01626. html>
kuantum melompat
adalah menarik mempertimbangkan tentang pembangunan teknis revolusioner potensial yang
boleh memperbesar riset dan aplikasi klinis sekedarnya itu akan menulis kembali seluruh
mendekati ke biomedicine. kedatangan polymerase reaksi berantai, large-insert cloning sistem
dan metode untuk murah, high-throughput dna peruntunan contoh demikian kemajuan yang
punya telah terjadi.
sepanjang sepanjang nhgri' bahasan perencanaan, ide lain mengangkat tentang teknologi dapat
dibandingkan melompat' itu bampak sejauh ini berhenti mengenai hampir fictional tetapi yang,
jika mereka dapat mencapai, akan mengubah dengan cepat biomedical riset dan pengamalan
klinis.
berikut tidak dimaksudkan untuk daftar mendalam, tetapi memarahkan kreatif bermimpi:
· kemampuan menentukan genotype sangat rendah berharga, mengizinkan persatuan belajar di
mana 2,000 individu dapat menyaring dengan tentang 400,000 penanda genetis untuk 10,000
atau kurang;
· kemampuan ke rangkaian dna berharga itu lebih rendah dengan empat ke lima pesanan jarak
daripada arus berharga, mengizinkan manusia genome untuk;menjadi sequenced untuk 1,000
atau kurang;
· kemampuan manyatukan panjang dna molekul ketelitian tinggi untuk 0.01 per markas,
mengizinkan perpaduan gene-sized sepotong dari dna tentang segala rangkaian untuk diantara 10
dan 10,000;
· kemampuan menentukan methylation keadaan dari semua dna di sel tunggal; dan
· kemampuan ke monitor keadaan protein di sel tunggal di eksprimen tunggal.
puncak halaman <file: /h: \smad-lock\dna\nature01626. html>
akibat
mempersiapkan visi untuk masa depan dari genomic riset telah keduanya menakutkan dan
menggembirakan. kesudian beratus-ratus ahli ke sukarelawan mereka boldest dan ide terbaik, ke
pergi wilayah mereka kepentingan diri dan terlibat dalam amat sangat membantahkan tentang
kesempatan dan prioritie, telah menambahkan kesempurnaan dan keberanian kepada hasil itu
tidak secara penuh mengantisipasi bila perencanaan proses mulai. kepada tingkat bahwa ini
artikel menangkap rasa kegembiraan gemblengan baru genomic, ini ke kredit mereka.
menyelesaikan daftar pengikut di proses perencanaan ini dapat menemukan <http: /www.
genome. gov/tentang/visi/acknowledgements>.

kata akhir tentang tepat lebarnya visi melafalkan disini. pilihan mempunyai untuk;menjadi
membuat diantara melukiskan luas melihat masa depan dari genomic riset dan memusatkan
banyak sedikit di peranan tertentu nhgri. mengenali peneliti itu dan orang ban banyak tertarik
akan memberi harapan ladang daripada tentang sumber pembiayaan bertanggung jawab, kami
telah memusat disini di pemandangan luas peluang ilmiah. kami punya, akan tetapi, mengenali
wilayah itu terutama sesuai dengan kepemimpinan dengan nhgri sepanjang artikel ini. ini
biasanya wilayah riset itu tidak dikhususkan untuk tertentu penyakit atau sistem organ, tetapi
punya lebih luas biomedical dan/atau implikasi sosial. bahkan di masih hal itu, 'rekanan sabda'
kelihatan waktu banyak dengan sengaja. kami mengharapkan punya persekutuan tidak hanya
dengan sumber pembiayaan umum lain, seperti lain 26 nih institut dan pusat, tetapi juga dengan
banyak para petugas pemerintah lain, dasar pribadi dan private-sector organisasi. tentu saja,
public-private persekutuan, seperti snp konsorsium, konsorsium peruntunan tikus dan
internasional hapmap proyek, sediakan model baru bertenaga untuk kumpulan data umum
pembuatan dengan dengan segera dan nilai besar pengaruhnya. jadi, banyak dari paling rangsang
kesempatan di genomic riset menyeberang batas tradisional definisi penyakit khusus, secara
sederhana menggambarkan gemblengan ilmiah, sumber pembiayaan dan umum melawan
perusahaan swasta. era baru akan tumbuh dengan subur terbaik di lingkungan dimana demikian
batas tradisional menjadi pernah banyak berongga kecil.
meskipun kesempatan menjelaskan disini dipikirkan untuk;menjadi sangat terjangkau,
permulaan resmi program khusus akan memerlukan lebih terperinci analisis. penghubung
prioritie dari tiap menjadikan lengkap harus mengalamatkan dipandang dari sudut sumber daya
terbatas ke riset dukungan. nhgri rencana mengeluarkan meninjau kembali pemberitahuan
program dan lain mengabulkan permohonan nanti tahun ini, membuktikan banyak pedoman
khusus ke peneliti diluar sekolah tentang rencana untuk implementasi visi ini. selanjutnya, di
genomic riset, kami telah belajar mengharapkan tak diduga. dari pengalaman masa lalu, ini akan
mengherankan (dan lebih mengecewakan) jika biologis, medis dan perhubungan sosial tidak
merubah di jalan tak dapat diramalkan. kenyataan itu memerlukan bahwa visi revisited secara
reguler.
kesimpulannya, berhasil kelengkapan bulan ini tujuan asli hgp memberanikan meluncurkan
dari gelombang baru untuk genomic riset, menjelajahi pemandangan baik sekali peluang itu
sekarang membuka atas sebelum kita. suka shakespeare, kami cenderung mengatakan, " apa
lewat kata pendahuluan" ( topan, bertindaklah ii, pemandangan 1. jika kita, suka arsitek tebal,
dapat desain dan bangun belum pernah terjadi ini dan struktur mulia, beristirahat di perusahaan
bedrock pondasi bagi hgp (figur 2 <file: /h: \smad-lock\dna\nature01626. html>, kemudian benar
memberi harapan dari genomic riset untuk menguntungkan umat manusia dapat mewujudkan.
" buat tidak rencana kecil; mereka tidak punya kegaiban menggerakkan darah laki-laki dan
mungkin akan mereka sendiri tidak mewujudkan. buat rencana besar; maksud tinggi di harap dan
kerjakan, ingat itu mulia, diagram logis sekali tercatat akan tidak mati, tetapi lama setelah kami
pergi akan merupakan suatu hal hidup, menyatakan sendiri dengan ever- tumbuh insistency"
menghubungkan dengan daniel burnham, arsitek).