sitogenetika

DEFINITION OF CYTOGENETICS

Cytogenetics is the study of

chromosomes.
Cytogenetics includes the
study of normal and
abnormal chromosomes,
and investigation of the
causes of chromosomal
abnormalities.
 CHROMOSOMES
PHOTO

Chromosomes are dense

bodies found in the
nucleus of cells. They
contain all the genetic
information necessary to
create a living being.

Photograph taken with a scanning electron microscope of several human

chromosomes. Source: J.B. Rattner and C.C. Lin, Cell 42 (1985), p. 291.
 CHROMOSOMES
ILLUSTRATION OF PAIRS

Chromosome pairs look a bit

like stick figures of people
each with two arms and two
legs.
The two arms are called the
short arms of the chromosome.
The two legs are called the
long arms of the chromosome.
These are joined in the middle
of the chromosome, which is
called the centromere.
 KARYOTYPE
Chromosomes are usually all
jumbled up and mixed together in
the nucleus of cells.

To study particular chromosomes,

they are organized by their size
and arranged in pairs. A full
complement of chromosomes
arranged from the largest to
smallest is called a karyotype.
Reverse-banded cell (top) with karyotype (below) from a normal male. Source: P.A. Benn and M.A. Perle, Chromosome Staining and
Banding Techniques, in Rooney & Czepulkowski, Human Cytogenetics: A Practical Approach (2nd ed. 1992), Vol. I at p.101.
When chromosomes are preparing to divide the DNA
replicates itself into two strands called chromatids

Replicating chromosome The same chromosome

under normal conditions
Telomere

Centromere

The two
chromatids

Telomere
 Chromosome nomenclature
Two arms
p (petite) and q (follows p in alphabet)

1-22 = autosome numbers

X, Y = sex chromosomes

Karyotype - the chromosome constitution

of an individual
 Three classes of chromosome

Metacentric -
centromere in middle

Submetacentric -
centromere distant
from middle

Acrocentric -
centromere at end
Clinical cytogenetics
looks at the morphology & organization of human
chromosomes
karyotyping important
white blood cells
block mitosis in metaphase
lyse the cells
fix
stain or use a probe
Clinical cytogenetics
situations where analysis is strongly recommended
problems with early growth & development
stillbirth & neonatal death
fertility problems
family history
neoplasia
pregnancy in older women
Chromosome staining
Q-banding quinacrine stain
G-banding giemsa stain
R-banding reverse banding
C-banding heterochromatin regions which remain
condensed
regions near centromere are heterochromatin
FISH fluorescence in situ hybridization
probes for specific genes or locations
probes tagged with fluorescent molecules
Spectral karyotyping
probes specific for each chromosome, different colors
chromosome identification
bands numbered from 1, starting near the centromere
short arm on the top, long arm on the bottom
centromere location key in identification
metacentric in center; arms about equal in length
submetacentric arms unequal
acrocentric centromere near one end
telocentric centromere at one end
acrocentric satellites on short arm
chromosome identification
G banding giemsa stain
unique staining pattern for each chromosome

p short arm,
on top
q long arm, on
bottom
special procedures
C banding staining of heterochromatin (condensed DNA)
region near centromere
High-resolution banding staining of less condensed
chromosome regions
non-staining regions on several chromosomes fragile
sites (fragile X mental retardation)
special procedures
FISH Fluorescence In Situ Hybridization
DNA probes for: specific chromosomes
specific regions
specific genes
detect chromosome rearrangements, abnormal numbers
THE HUMAN GENOME
HUMAN CHROMOSOMES

There are 46 chromosomes

in human cells. These
consist of 22 autosomal
pairs (one of each type
contributed by the mother
and one of each type
contributed by the father),
and two sex chromosomes.
 SEX CHROMOSOMES
The sex chromosomes are referred to by the letters
x and y. Females have two x chromosomes.
Males have one x and one y chromosome.
46,XX = female 46,XY = male

Giemsa banding (G-banding)

 GENES
Genes are segments of chromosomes which contain
particular genetic information.
Together the genes within our chromosomes contain the
entire blueprint for all human life.
There are about 35,000 genes in the human genome.
 DNA: THE MOLECULE OF LIFE

Source: Human Genome Project http://www.ornl.gov/hgmis/graphics/slides/images1.html

THE DISCOVERY OF DNA

The structure of DNA was discovered by James

Watson and Francis Crick in 1953. Watson was
an American biochemist working at Cambridges
Cavendish Laboratory. Crick was a British
physicist/biologist.
For their discovery, Watson and Crick were
awarded the Nobel Prize in 1962.
Chromosome abnormalities
euploidy or polyploidy
multiples of the N number of chromosomes
haploid 1N or 23 chromosomes
diploid 2N or 46 chromosomes
triploid 3N or 69 chromosomes
tetraploid 4N or 92 chromosomes
Chromosome abnormalities
triploid 3N
due to dispermy
found in 15-18% of
spontaneous abortions

enlarged head
fusion of fingers & toes
malformations of mouth,
eyes & genitals
Chromosome abnormalities
tetraploid 4N or 92 chromosomes
present in ~5% of spontaneous abortions
Chromosome abnormalities
changes in number that are not a multiple of 23
addition or deletion of individual chromosomes
aneuploidy 45 or 47 chromosomes
monosomy 45 chromosomes
trisomy 47 chromosomes
aneuploidy
monosomy one of a pair missing (usually lethal)
karyotype: 45, XX -13 or 45, X
trisomy three of one chromosome (XXY; trisomy 21)
karyotype: 47, XY +13 or 47, XX +13

non-disjunction is cause
trisomy of autosomes
trisomy 13 Patau syndrome (47, +13)
1 in 15,000 live births
condition lethal
phenotype
facial malformations
eye defects
extra fingers or toes
malformations of brain & nervous
system
congenital heart defects
parental age is a factor
trisomy of autosomes
trisomy 18 Edwards syndrome (47, +18)
80% of live births are female
phenotype
small at birth, grow slowly
mentally retarded
clenched fists; 2nd & 5th fingers overlap 3rd & 4th
malformed feet; heart malformations common
parental age is
a factor
trisomy of autosomes
trisomy 21 Down syndrome (47, +21) most common trisomy
trisomy of autosomes
trisomy 21 Down syndrome (47, +21) most common trisomy
1 in 900 live births
leading cause of mental retardation and heart defects
phenotype
distinctive skin fold near eye epicanthic fold
spots in iris Brushfield spots
wide skull, flatter than normal at the back
tongue often furrowed and protruding
congenital heart defects in ~40% of cases
physical growth, behavior and mental development are
retarded
prone to respiratory infections
contract leukemia at higher rate than normal
parental age is a factor
CHROMOSOME ABNORMALITIES

Cancer can result when chromosomes

become damaged or when
chromosome replication goes awry.
There are two major types of
chromosomal damage:
Numerical abnormalities
Structural abnormalities
 NUMERICAL
ABNORMALITIES

Numerical abnormalities occur when cells lack the usual 46

pairs of chromosomes. Examples of numerical abnormalities
are monosomy (only 1 chromosome of a pair), trisomy (3
chromosomes instead of 2), tetrasomy (4 chromosomes instead
of 2), et cetera.
 4N
First meiotic
division NORMAL SEPARATION

2N
Second meiotic
division

Gametes N

Fertilization

Zygotes 2N

NORMAL ZYGOTE
First meiotic
division NONDISJUNCTION

Second meiotic
division

Gametes

Fertilization

Zygotes

TRISOMIC ZYGOTE MONOSOMIC ZYGOTE

 STRUCTURAL
ABNORMALITIES

Structural abnormalities occur

when cells have the usual 46
pairs of chromosomes, but the
normal structure of the
chromosomes has been altered.
Sometimes a chromosome will
break into two pieces. This is
called a chromosome break.
Sometimes one of the pieces is
lost. This is called a deletion.
Either the long or the small arm
of a chromosome can be
deleted.
CHROMOSOME TRANSLOCATION

Sometimes two chromosomes will break in half and the four

pieces will reassemble with each other improperly. This is
called a chromosome translocation.
Six main types

Deletion
Ring chromosome
Duplication
Isochromosome
Inversion
paracentric & pericentric
Translocation
Robertsonian & reciprocal
Kelainan Struktur kromosom

Delesi
Duplikasi

Inversi

Translokasi
 Deletion
Involves loss of part of a
chromosome
Results in monosomy of
that chromosomal
segment
Clinical effects due to
Insufficient gene products
Unmasking of mutant
alleles on normal Before After
chromosome deletion deletion
 Two types of deletion

Terminal Interstitial
Wolf-Hirschhorn syndrome

deletion of
distal arm of
chromosome
4p

growth and
mental
retardation

seizures
 Ring chromosome
Breaks occur in both arms of a chromosome.
The two broken ends anneal; the two acentric
fragments are lost.

Results in double deletion (in p and in q).

Epilepsy, mental retardation and craniofacial abnormalities
Duplication

Trisomy of
duplicated
segment

Direct Inverted
 Isochromosome
Mirror image chromosome
Loss of one arm with duplication of other

Loss of p-arm Duplication of q-arm

 Inversion
Two breaks in one chromosome
The fragment generated rotates 180o and
reinserts into the chromosome

Pericentric - involves p and q arm Paracentric - involves only one arm

 Translocation - exchange of
chromosomal material between two or more
chromosomes

Reciprocal
Robertsonian

If no essential chromosome material

lost or genes damaged then the
individual is clinically normal
However, there is an increased chance
of chromosomally unbalanced
offspring
 Reciprocal Translocation
Involves two chromosomes
One break in each chromosome
The two chromosomes exchange broken segments

Before translocation After translocation

 Robertsonian translocation
Named after W. R. B. Robertson who first
identified them in grasshoppers in 1916

Most common structural chromosome

abnormality in humans
Frequency = 1/1000 livebirths

Involves two acrocentric chromosomes

Two types
Homologous acrocentrics involved
Non-Homologous acrocentrics involved
 Homologous acrocentric, i.e. chromosome 14

lost

+ =

Non-homologous acrocentric, i.e. chromosomes 14 &

lost

+ =
Chromosome abnormalities in humans

Spermatozoa 10%
Mature oocytes 25%
Spontaneous miscarriage 50%
Live births 0.5-1%
Most due to maternal meiotic non
disjunction
Strongly related to maternal age
Natural selection at work
Chromosome abnormalities in miscarriages
Incidence
%
Trisomy 13 2
Trisomy 16 15
Trisomy 18 3
Trisomy 21 5
Other Trisomy 25

Monosomy X 20
Triploidy 15
Tetraploidy 5
Other 10
Chromosome abnormalities in newborns
Incidence / 10,000
births
Trisomy 13 2
Trisomy 18 3
Trisomy 21 15

45,X 1
47,XXX 10
47,XXY 10
47,XYY 10
Unbalanced 10
Balanced 30
Total 90
 Chromosome abnormalities

Triploidy rare at birth lethal

Most common in spontaneous miscarriages

Trisomy 16 Completely lethal. Cause unknown

95% miscarry
Trisomy 13
&18 80% miscarry

50% miscarry
Trisomy 21
1% at conception
Klinefelters 98% miscarry, probably mosaic survive

45X
Trisomi Autosom

Down Sindrom
Sindroma trisomi-13
/Sindroma Patau (47,+13)
Sindroma Edwards/trisomi-
18 (47,+18)
SINDROM DOWN

GAGAL PISAH

TRISOMI 21

GENOTIP: 46,XY. 46,XX

PENOTIP:
 Down Sindrom (Trisomi 21)
Mongolisme dengan perbandingan 1:600
dan semakin meningkat sesuai dengan usia
ibu
Sitologi :DS tripel 21(47,XY,+21) atau
translokasi :46,XY,t(14q21q)
Tanda :
1. Tubuh pendek dengan kaki atau lengan
bengkok
2. Wajah khas yaitu bulat dengan ujung lidah
yang besar, mulut selalu terbuka, hidung
lebar dan datar, epikantus, iris mata kadang
berbintik-bintik disebut Brushfield
3. Retardasi mental (25-70)
4. Biasanya memiliki kelainan jantung dan
tidak resisten pada penyakit
KROMOSOM 21
Trisomi 21
Tanda dari Down Sindrom
SIMIAN CREASE
NDJ Down Sindrom terjadi pada
saat oogenesis
ESTIMASI RISIKO S. DOWN BERDASARKAN
USIA MATERNAL
Sindroma Patau
 Sindroma trisomi-13 /Sindroma
Patau (47,+13)
1. 1:20.000
2. Kematian pada usia yg sgt muda
(3 bln)
3. Tanda:cacat mental, tuli, celah
bibir dan palatum, polidaktili,
kelainan organ utama
SINDROM EDWARD

GAGAL PISAH:

E/ : TRISOMI 18

GENOTIP: 46,XY . 46.XX

PENOTIP :
Sex chromosomes and
sex chromosome
abnormalities
Females = 46,XX

Males = 46,XY
 X-chromosome
Length = 155 million base pair

Contains 931 genes (Oct 2005)

Y-chromosome
Length = 58 million base pairs

Contains 104 genes (Oct 2005)

Examples of abnormalities in sex
chromosomes

Turner syndrome
1 in 1500 - 5000 live born females

Klinefelter syndrome
1 in 1000 live born males
Turner syndrome

Short stature

Webbed neck

Lack of secondary
sexual characteristics

Amenorrhea (failure to
menstruate)
 Turner karyotype
45,X 55%

46,X with abnormal X 15%

Deletion
Isochromosome
Ring
Mosaic 30%
X/XX
X/XY
X/XXX etc.
SINDROM TURNER

GAGAL PISAH PADA

MITOSIS, MIOSIS I dan
MIOSIS II

GENOTIP: 45,X

PENOTUP:
 Monosomi (Sindroma
Turner )

Fenotip : perempuan, Genotip : 45,X

1:3000, 90 % abortus
Tanda : pendek, leher pendek, dan
bersayap, tanda sekunder tdk
berkembang, Pada waktu bayi tampak
adanya kulit tambahan di leher
tdk ada retardasi mental
Sex kromatin (-)
Terapi dgn estrogen
NDJ Sindrom Turner
Klinefelter syndrome
Lower IQ than sibs

Tall stature

Poor muscle tone

Reduced secondary
sexual characteristics

Gynaecomastia
(male breasts)

Small testes/infertility
 Klinefelter karyotype

47,XXY

The discovery of the

karyotype of Klinefelter was
the first demonstration that
sex in humans is determined
by the presence of the Y
rather than the number of X
chromosomes
SINDROM KLINEFELTER

GAGAL PISAH:
MITOSIS.MIOSIS I DAN
MIOSIS II

47,XXY

PENOTIP:
Sindroma Klinefelter

Fenotip pria tapi tanda-tanda

sekunder wanita berkembang
(tumbuh payudara, pertumbuhan
rambut kurang, lengan dan kaki
ekstrim panjang sehingga tubuh
tampak tinggi, suara tinggi sepert
wanita, testis kecil dan
spermatozoa tdk terbentuk tapi
alat genitalia normal.
Sek kromatin positip
Sebagian besar ok NDJ ovum
(70%)
Sindroma XYY
Cri du - Chat
Cri du Chat

Terminal
deletion
5p15

Cries like cat

Mental
retardation
Diagnosis of chromosome abnormalities
Child born
take blood and look at
lymphocytes
Unborn child
Prenatal Diagnosis
Chorionic villus sampling (CVS)
Amniocentesis (AF)

Fetal Blood Sampling (FBS)

Screening

Both in first and second trimester

Serum

Ultrasound

Indicates which should go forward

for invasive procedure
Prenatal Diagnosis
CVS
Performed around 10-12 weeks
Transcervical or transvaginal
Aspirate or biopsy chorionic villi
Examine by direct prep or culture
Direct prep cytotrophoblast
display spontaneous activity
can get metaphases result in 24
hours
Culture chorionic mesoderm for
good quality G band takes 8-14
days
1% risk miscarriage
CVS
 Prenatal Diagnosis
Amniocentesis

Most common method used

Usually perform around 16 weeks
10-20 ml amniotic fluid
Culture for 8-14 days
Do G banding
Can do a quick diagnosis on uncultured
amniocytes using FISH or QF-PCR
Only examine a few chromosomes
0.5-1% miscarriage rate
Amniocentesis
 Molecular Cytogenetics

FISH
Use DNA probes for specific chromosomes
Can paint metaphase
Useful for quick result and identifying small
areas
Eg deletions, ESACs

QF-PCR
Quantitative fluorescent PCR
Use polymorphic sites to define number of
copies present
Useful for quick result in prenatal diagnosis
 Quantitative Fluorescent PCR

Trisomy detection in prenatal samples

Hypervariable
region on
chromosome 21
amplified by F- Ratio: 1 : 1 :
PCR 1

Ratio: 1 : 2
Quick result from Amniocentesis
FISH
Use probes for 13,21 and X, Y, 18 on two different
slides
takes 24 hours

QF-PCR
Use polymorphic markers for chromosomes 13, 18,
21
Results in 24 hours
Becoming more common

Can only detect abnormalities for these

chromosomes
Usually go on and do full karyotype - ???
The future

Fetal cells in the maternal

circulation
Free fetal DNA in maternal
plasma

If diagnostic no need for

CVS or amniocentesis to
detect chromosome
abnormality
Human
Genetics
Timothy G. Standish, Ph.
D.
 The Madness of King George III
Partly as a result of the erratic behavior of King
George III the American colonies decided to break
away from the United Kingdom
Other members of King Georges family also
exhibited strange behavior with dire
consequences. These included Mary Queen of
Scots and her son James I both of whom were
beheaded.
Because madness seems to have run in the family,
it is thought thought to have a genetic basis
Acute intermittent porphyria seems to be
consistent with the symptoms exhibited by
George III
 Human Heredity Is Not Unique
The genes of humans behave in the same
way as genes of other organisms
Of the estimated 100,000 human genes,
most are identical in all humans
The relatively small number of polymorphic
genes in humans account for only part of the
variability that we see between humans
While each human (except for identical
twins) has a unique set of genetic
information, variation between humans also
results from differences in the environment
 Politics and Genetics
Because we are talking about how humans are
when we are talking about human genetics, there
can be lots of controversy when traits are seen as
relating to race, gender or other sensitive issues
This is particularly true when we start to talk about
the genetics of behavior
Nazis and other extreme right wing politicians see
human worth and behavior being based on
genetics
Communists and other extreme leftwing
politicians see humans as infinitely pliable and
molded by their environment not genetics
Simple Dominant/Recessive Traits

Many human genes are inherited as

dominant or recessive traits just like the
traits Mendel studied in peas
Ear lobes provide an example of this:

Unattached Attached ear

ear lobes are lobes are
inherited as a inherited as a
dominant recessive
trait. trait.
Simple Dominant/Recessive Traits

Having a bent little finger is a dominant trait

Dominant/Recessive Human Traits
Albinism - There are a number of different types of
albinism, but each is characterized by an absence of
pigment from the skin, eyes and hair. Albino
individuals typically have very pale white skin, light
blue or pink eyes, and light blond or white hair.
Albinism is a recessive trait.
Brown teeth - Teeth have a brown color that is not the
result of poor oral hygiene or antibiotics taken as a
child. White teeth are dominant.
Dominant/Recessive Human Traits
Cleft chin - A noticeable indentation at the center of
the chin. For examples think of Kirk Douglas and
Michael Jackson (after plastic surgery). Having a cleft
chin is dominant to a smooth chin.
Double-jointed thumbs - This is commonly called a
hitchhiker's thumb. The thumb can bend back at
almost 90 degrees. Hitchhiker's thumb is a recessive
trait, but it may vary in its expression.
Dominant/Recessive Human Traits
Hand folding - When the hands are folded either the
left or right thumb will be on top. Left thumb on top
is dominant.
Mid-digital hair - Hair growing from the middle
section of each finger. Hair presence is dominant.
PTC tasting - Phenylthiocarbamide (PTC) is a bitter
tasting chemical that cannot be tasted by some
individuals. PTC tasters taste PTC as bitter, non-
tasters taste nothing when given PTC. Tasting is
dominant to the inability to taste PTC.
Dominant/Recessive Human Traits
Tongue rolling - Tongue rolling is the ability to
form a tube with your tongue. Rolling is
dominant.
Widow's peak - A sharp point in the hairline
that points toward the nose. Having a widow's
peak is dominant to a smooth hairline.
 Sex Influenced Human Traits
Baldness - Loss of hair from the scalp following
puberty. A sex influenced trait that is most commonly
fully expressed (as a dominant trait) in males, but
carried on an autosome
Index finger shorter than ring finger - The index
finger (next to your thumb) is longer than the ring
finger (next to your little finger). Check the class data
to see if the frequency is different for the different
sexes.
 Sex Linked Human Traits
Color blindness - Inability to distinguish
between colors of the same intensity. There
may be two types, red green color blindness in
which individuals perceive red and green as the
same color, and complete color blindness in
which all colors are perceived as being the same
and vision is the functional equivalent of black
and white television. Both types of
colorblindness are sex linked traits.
 Specific Human Traits
Dimples - Round indentations in the cheeks when
smiling, not lines or clefts.
Freckles - Small patches of darker pigmented skin on
various parts of the body and most visible in those
areas commonly exposed to the sun. These may be
present on both dark and light skinned individuals.
Hair whorling - These may be referred to as cowlicks.
Areas in which hair grows from your scalp in a whorl
instead of in a given direction.
 Specific Human Traits
Myopia - Short sightedness, the inability to see far off
objects without correction by glasses or contacts
Polydactyly - Having more than five digits on each
hand and foot.
S-methyl thioester smeller - S-methyl thioesters are
produced in the urine after consumption of asparagus.
Some individuals cannot smell this substance. If you
smell a strong odor on urination after eating at least 5
asparagas spears, you are an S-methyl thioester
smeller.
 Specific Human Traits
White forelock - A white patch of hair at the
front of the scalp.
 Multiple Alleles
Eye color is determined by more
than one gene
Thus eye color appears to vary on an almost
continuous scale from brown to green to gray
to blue
Eye color is determined by two genes, one
controls texture of the iris which refracts light
to make blue. A second determines relative
abundance of melanin. When a small amount
of melanin is present, green eyes result while
brown and black eyes result from relatively
increasing amounts of melanin
Multiple Alleles
Hair color is determined
by more than one gene
Thus hair color appears to
vary on an almost
continuous scale from
black to brown to blond to
red
The brown and black
pigment is melanin
The red pigment is an iron
containing molecule
GENETIC DS

SINGLE GEN ( MENDELISME )

MULTIFACTORIAL
CHROMESOMES DS
SOMATIC MUTATION-
CANCER
GENETIC DS ???????

CONGENITAL NOT GENETIC:

ALCOHOL FETAL SYNDROME
CONGENITAL NOT GENETIC:
HUTINGTON DS
MUSCULAR DYSTROPHY:
DUCHNE & BEKER
GENETIC & CONGENITAL:
DOWN SYNDROME
PEWARISAN SIFAT

MONOGENIK
Dominan Autosom
Resesif Autosom

Alel Ganda

Terangkai Kelamin

POLIGENIK
Symbol used in pedigree
 DOMONANCE / RECESSIVE

DOMINANCE
RECESSIVE
HETEROZYGOUS
HETEROZYGOUS
a A
Aa A a
mutasi

HOMOZYGOUS HOMOZYGOUS

A A a
AA a
aa
AUTOSOMAL DOMINANT

AFFECTS EITHER SEX

TRANSMITTED BY EITHER
SEX
AN AFFECTED PERSON
USSUALLY
HAS AT LEAST ONE
AFFECTED PARENT
Autosomal dominant
DOMINAN AUTOSOM
Disebabkan adanya satu atau
sepasang gen mutan abnormal
pada autosom
Gen mutan bersifat dominan
Contoh :
Akondroplasia
Retinoblastoma
Poliposis Kolon
Khorea Huntington
Sklerosis Tuberosa
Polidaktili
DOMINAN AUTOSOM
Penderita hanya butuh satu alel
dominan. Individu heterozigot sakit
paling banyak dijumpai
Penderita homozigot sakit akan
menderita penyakit lebih berat
dibanding individu heterozigot sakit
sangat jarang (stillbirth, neonatal death,
dll)
Penderita mempunyai sekurangnya
salah stau orang tua yang juga sakit
Individu tidak sakit tidak akan
mewariskan gen abnormal
Anak laki-laki dan perempuan punya
kesempatan yang sama
DOMINAN AUTOSOM

Pola perkawinan
Heterozigot sakit dengan
individu normal
Heterozigot sakit dengan
heterozigot sakit
Homozigot sakit dengan
individu normal
Homozigot sakit dengan
heterozigot sakit mungkin
tidak pernah dijumpai
DOMINAN AUTOSOM

Fresh mutation
Seleksi alam
Ekspresivitas
Penetransi
Manisfestasi pada umur tua
Antisipasi
Pengaruh jenis kelamin
Imprinting gen
AUTOSOMAL RECESSIVE

AFFECTED EITHER SEX

AFFECTED PEOPLE
USSUALLY BORN TO
UNAFFECTED PARENT
AN INCREASE INCIDENCE OF
PARENTAL CONSANGUINITY
Autosomal recessive
RESESIF AUTOSOM

Disebabkan sepasang gen mutan

resesif yang terletak pada autosom
Contoh :
Albino
Galaktosemia
Fenilketonuria
Penyakit Wilson
Osteogenesis imperfecta
Glaukoma kongenital
Ichtyosis Congenita
RESESIF AUTOSOM
Setiap individu sakit adalah homozigot
resesif
Kedua orangtua membawa satu alel gen
mutan resesif
Individu sakit mempunyai orang tua
yang keduanya normal carier
Individu dengan satu alel resesif
(heterozigot) tidak menunjukkan
kelainan
Rasio anak normal dan anak sakit pada
perkawinan dua individu heterozigot =
3:1
Frekuensi meningkat dengan
perkawinan keluarga
ALEL GANDA

Terdapat tiga atau lebih

alternatif gen yang menempati
suatu lokus dalam pasangan
kromosom
Gen yang membentuk alel
ganda dapat resesif, dominan
atau kodominan
Contoh : Golongan darah
ABO, Hemoglobin, Kulit
kelinci
TERANGKAI KELAMIN
Kromosom X membawa gen-gen vital di
samping gen kewanitaan, sedangkan
kromosom Y hanya mengandung gen
untuk kepriaan
Terdapat mekanisme untuk
menyeimbangkan bahan genetik
inaktivasi kromosom X (hipotesis Lyon)
Salah satu dari kromosom X pada sel
somatik wanita normal diinaktifkan
secara genetik
Kromosom inaktif berasal dari
maternal atau paternal
Inaktivasi terjadi pada perkembangan
embriologis, sekali diinaktivasi maka
tidak aktif selamanya kondensasi
X-LINKED DOMINANT

AFFECTED EITHER SEX, F >

M
FEMALE ARE OFTEN MORE
MILDLY AND MORE
VARIABLY AFFECTED THAN
MALES
FOR AN AFFECTED MALES,
ALL HIS DOUGHTER BUT
NONE OF HIS SON ARE
AFFECTED
X-linked dominant
TERANGKAI-X DOMINAN

Disebabkan adanya satu gen

mutan pada salah satu
kromosom X pada wanita XX
sudah menimbulkan penyakit
Peluang wanita dan pria sama
besar, tetapi wanita
heterozigot akan menderita
penyakit lebih ringan
Contoh : Rakhitis resisten
vitamin D, Gigi Cokelat
X-LINKED RECESSIVE

AFFECTED MAINLY MALES

AFFECTED MALES ARE
USSUALLY BORN TO
UNAFFECTED PARENT. MOTHER
IS NORMALLY ASYMPTOMATIC
CARRIERT, AND MAY HAVE
AFFECTED MALES RELATIVES
FEMALE MAY BE AFFECTED IF
FATHER IS AFFECTED AND
MOTHER IS A CARRIER
TERANGKAI X RESESIF

Disebabkan gen mutan resesif

pada kromosom X
Penderita pria jauh lebih banyak
dibanding wanita atau penderita
dapat jadi hanya pria saja
Contoh :
Buta warna merah hijau
Hemofilia
Anadontia
TERANGKAI-X RESESIF

Insidensi penyakit pada laki-laki

lebih besar daripada wanita.
Frekuensi penyakit pada wanita
adalah kuadrat frekuensi penyakit
pada pria
Gen XR diwariskan dari pria sakit
ke semua anak perempuannya
Gen XR tidak pernah diwariskan
langsung dari ayah kepada anak
laki-lakinya
Gen dapat diwariskan dari wanita
carier
 CARRIER DETECTION

A.D A.R X-R

*
TERANGKAI-Y

Pewarisan holandrik, hanya

diwariskan pria ke keturunan
laki-lakinya
Mutasi jenis apapun
menimbulkan efek
Contoh : daun telinga
berambut
PEWARISAN POLIGENIK

Penyimpangan cara pewarisan

Mendel
Karakter atau sifat tertentu
ditentukan tidak hanya sepasang
gen, tapi beberapa atau beberapa
pasang gen
Karakter bersifat kuantitatif
Poligen tidak sama dengan alel
ganda
Contoh :
Tinggi badan
Warna kulit
Picture slide