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BASIC

GENETICS
Colada, Erika Lei D.
Gloriani, Airam Eulizhene B.
Kusi, Abigail
Layague, Peter Paul
Mendoza, Aira Joy C.
Pagala, Vida Angela D.
Rotairo, Lorraine B.

CLASSIC and population


genetics

Classic Genetics
GENETICS: study of inheritance or
the transmission of characteristics
from parent to offspring
23
pairs of chromosomes; 22
autosomes, 1 sex chromosomes
(XX) females; (XY) males

Classic Genetics

Importance:
Inheritance of blood groups
antigens and the testing for disease
markers on a molecular level
All areas for transfusion medicine
are influenced by genetics, including
HLA typing, cell processing,
parentage studies, viral testing and
blood services.

REMEMBER!
Phenotype the antigens present on all
blood cells
Genotype controls what antigens may
be expressed on the cell
Homozygous contains only one allele of
the allelic pair (DD, dd); also called pure
Heterozygous contains one of each
member of the gene pair (Dd); also called
hybrid

REMEMBER!
Dominant the allele that expresses itself
at the expense of an alternate allele
Recessive an allele whose expression is
suppressed in the presence of a dominant
allele
Allele one alternative form of a given
allelic pair
Punnett square a diagram for predicting
the results of a genetic cross between
individuals of known genetic makeup

Population Genetics
Mendel
s Laws
of
Inherita
nce

HardyWeinbu
rg
Principl
e

Inherita
nce
Pattern
s

History of Early Genetics

17th century Carolus Linnaeus

1859 Charles Darwin

Classification system of living things, unit of


specules as principal definition
On the Origin of Species Natural selection

1800s Gregor Mendel

Father of Genetics, determined the physical


traits to be due to factors he called
elementen or genes
Observed seed shape, seed color, flower color,
flower position, pod shape, pod color, etc.

MENDELS LAWS OF
INHERITANCE
a.

b.
c.

Law of Independent/Random
Segregation
Law of Independent Assortment
Law of Dominance

a. Law of Segregation
During gamete formation, each
member of the gene pair separates
from the other member to form the
genetic constitution of the gamete
Alleles for a trait are then
"recombined" at fertilization,
producing the genotype for the traits
of the offspring.

EXPERIMENT

Parental
or pure
First filial

P Generation
(true-breeding
parents)

F1 Generation
(hybrids)

Red
flowers

White
flowers

All plants had red flowers

F2 Generation

Second
filial

red
flowered
plants

white
flowered
plants

b. Law of Independent Assortment


Genes for different traits are inherited
separately from each other
Allows possible combinations of genes
to occur in the offspring
This law applies only to genes on
different, non-homologous
chromosomes or those far apart on
the same chromosome

b. Law of Independent Assortment


Monohybrid individuals that are
heterozygous to each other
Monohybrid cross a cross between
such heterozygotes
Dihybrid Product of crossing two
true-breeding parents differing in two
characters, heterozygous for both
characters
Dihybrid cross a cross between F
1
dihybrids

EXPERIMENT
P Generation

YYRR

yyrr

Gametes YR
F1 Generation

yr
YyRr

Hypothesis of
Hypothesis of
dependent assortment independent assortment
Sperm
or
Predicted
1
/4 YR 1/4 Yr 1/4 yR 1/4 yr
offspring of
Sperm
F2 generation
1
/2 YR 1/2 yr
1
/4 YR
YYRR YYRr YyRR YyRr
1
/2 YR
YYRR YyRr
1
/4 Yr
Eggs
YYRr YYrr YyRr Yyrr
Eggs
1
/2 yr
1
YyRr yyrr
/4 yR
YyRR YyRr yyRR yyRr
3
1
/4
/4
1
/4 yr
Phenotypic ratio 3:1
YyRr Yyrr yyRr yyrr
Predictions

/16

/16

/16

/16

Phenotypic ratio 9:3:3:1


RESULTS

315

108

101

32

Phenotypic ratio approximately 9:3:3:1

c. Law of Dominance

In a cross of pure parents for


contrasting traits, only one form of the
trait will appear in the next generation.
Offspring that are hybrid for a trait will
have only the dominant trait in the
phenotype.
The more complex the genetic material
of an organism, the greater uniqueness
of the one organism from another
organism.

GENOTYPE SYMBOL

GENOTYPE VOCAB

PHENOTYPE

TT

homozygous
DOMINANT
or
pure tall

tall

Tt

heterozygous
or
hybrid

tall

tt

homozygous
RECESSIVE
or
pure short

short

c. Law of Dominance
TAL
L
ste
ms

Gree
n pea
pods

short

stem
s
Yello
w
seed
s
Yello
w
pea
pods

TAL
L

ste
ms
Gree
n
seed
s
Gree
n pea
pods

Yello
w
seed
s

Hardy-Weinburg
principle
G. H. Hardy, a mathematician, and
W. Weinberg, a physician,
developed a mathematical formula
that allowed the study of
Mendelian inheritance in great
detail

The Hardy-Weinberg formula

p + q = 1, in which
p equals the gene frequency of the
dominant allele and
q is the frequency of the recessive
allele
can also be stated p2 + 2pq + q2 = 1 and
specifically addresses questions about
recessive traits and how they can be
persistent in populations

Criteria for Use of the Hardy-Weinberg


Formula

The population studied must be large


Mating among all individuals must be
random
Mutations must not occur in parents
or offspring
There must be no migration,
differential fertility, or mortality of
genotypes studied

EXAMPLE #1

If in our example we tested 1,000


random blood donors for the D antigen
and found that DD and Dd (Rh-positive)
occurred in 84 percent of the
population, and dd (Rh-negative)
occurred in 16 percent, the gene
frequency calculations would be
performed as follows:

EXAMPLE #1

p = gene frequency of D
q = gene frequency of d
p2 = DD, 2pq = Dd, which combined are 0.84
q2 = dd, which is 0.16
q = square root of 0.16, which is 0.4
p+q=1
p=1-q
p = 1 - 0.4
p = 0.6

EXAMPLE #2

Albinismis a rare genetically inherited trait


that is only expressed in the phenotype of
homozygousrecessiveindividuals (aa). The
most characteristic symptom is a marked
deficiency in the skin and hair pigment
melanin. This condition can occur among
any human group as well as among other
animal species. The average human
frequency of albinism in North America is
only about 1in20,000.

EXAMPLE #2

Referring back to the Hardy-Weinberg


equation(p + 2pq + q = 1), the frequency
of homozygous recessive individuals (aa) in
a population isq. Therefore, in North
America the following must be truefor
albinism:
q = 1/20,000 = .00005
By taking the square root of both sides of
this equation, we get: (Note: the numbers
in this example are rounded off
forsimplification.)

EXAMPLE #3

In other words, the frequency of the recessive


albinism allele (a) is .00707. Knowing one of
the two variables (q) in the Hardy-Weinberg
equation, it is easy to solve for the other (p).
p=1- q
p=1- 0.007
p= 0.993
The frequency of the dominant, normal
allele (A) is, therefore, 0.99293.

Inheritance patterns

Pedigree Analysis

A diagram that shows


appearance of phenotypes for a
single trait in a group of related
individuals from one generation
to the next.

REMEMBER!

Blood type is determined by genetic


inherited patterns.
Phenotype - observable trait
Genotype - actual genetic make-up
Blood type is determined by the antigen
present on the RBC.

REMEMBER!

Genes - unit of inheritance on a


chromosome. They are located on specific
areas of the cells called genetic loci.
Alleles - form or different forms of a gene
of a given loci. (Each gene resides at a
specific locus on a specific chromosome)

Ex: A, B and O alleles on the ABO gene locus.


ABO genes locus 9

Polymorphic - having two or more alleles


at a given locus. (Rh system)

Inheritance Pattern:

Co-dominant (equal expression of a gene


on an individual)
A.

B.

two alleles that express themselves


equally in the presence of each other
A and B are codominant

Recessive or dominant ( only one alleles


is expressed on the cell)
A.

Both and B are dominant to O, therefore O


is recessive

Homozygous vs. Heterozygous inheritance

Homozygous - 2 alleles for a given


trait are the same-genotype are identical
genes
Heterozygous - 2 alleles are inherited
are different-genotype are different.
Agglutination reactions will be effected
by inheritance pattern.
Homozygous pattern - stronger reactions
Heterozygous pattern - weaker reactions

Homozygous parents

Blood type A and O


parents

Blood type A IAIA


O- i

Offsprings

are all IAi

Type B and O parents

Blood type B IBIB


O- i

Offsprings

are all IBi

Type A and B parents

Blood type A IAIA

Blood type B-IBIB


IAIB

Offsprings

are all

Heterozygous parents
Type A(I i) and O parent
A

Type B(IBi) and O parent

Type A (I i) and Type


B
B(I i)
A

Mendelian Pedigree Patterns:

Autosomal recessive two


copies of an abnormal gene
must be present in order for
the disease or trait to develop

X linked dominant

A mode
ofgenetic
inheritance
by which a
dominant
geneis
carried on
theX
chromosom
e.

X linked dominant

Example:
Xgblood group system,is the
onlyblood groupin which the
antigen-encoding genesare
located on the Xchromosome.

X linked recessive

A mode
ofinheritancein
which amutationin
ageneon theX
chromosomecause
s the phenotype to
be expressed in
males and in
females who are
homozygous for the
gene mutation

CELLULAR
GENETICS

Mitosis and meiosis

Why Do Cells Divide?

For growth, repair,


and reproduction.

MITOSIS
Organisms grow by the
addition of cells
In multicellular organism
some of these cells
perform functions different
from other cells.

Cell Division vs. Nuclear


Division

Cytokinesis: The actual division of


the cell into two new cells.

Mitosis: The division of the nucleus


of the cell into two new nuclei.

NOTE:

Sometimes cells go through


mitosis without going through
cytokinesis.

gene- basic unit of heredity; codes for a


REMEMBER!

specific trait
locus- the specific location of a gene on a
chromosome (locus - plural loci)
genome- the total hereditary endowment
of DNA of a cell or organism
somatic cell- all body cells except
reproductive cells
gamete- reproductive cells (i.e. sperm &
eggs)
chromosome- elongate cellular structure
composed of DNA and protein - they are
the vehicles which carry DNA in cells

REMEMBER!

Sister chromatids - identical structures that result


from chromosome replication, formed during S phase
diploid (2n)- cellular condition where each
chromosome type is represented by two homologous
chromosomes
haploid (n)- cellular condition where each
chromosome type is represented by only one
chromosome
homologous chromosome- chromosome of the same
size and shape which carry the same type of genes
chromatid- one of two duplicated chromosomes
connected at the centromere
centromere- region of chromosome where
microtubules attach during mitosis and meiosis

Anatomy of a
Chromosome
p -arm

centromere

q-arm

chromatids
telomere

Centromere - point
where sister
chromatids are
joined together
P=short arm;
upward
Q=long arm;
downward
Telomere-tips of
chromosome

How Do Cells Divide?

Cell cycle - sequence of


phases in the life cycle
of the cell

Cell Cycle
G1 phaseGrowth
S phase- DNA
replication
G2 phaseGrowth and
preparation for
mitosis
M- Mitosis

STAGES OF MITOSIS

Interphase
Prophase
Metaphase
Anaphase
Telophase

Interphase
Interphaseis the
"resting" stage
between cell
divisions.
During this period,
cells are
synthesizing RNA
and protein and
chromatin is
uncondensed.

Prophase
Prophase- the
first stage of
mitosis.
The chromosomes
condense and
become visible
The centrioles
form and move
toward opposite

Prophase
The nuclear
membrane
dissolves
The mitotic spindle
forms (from the
centrioles in
animal cells)
Spindle fibers from
each centriole
attach to each

Metaphase
The centrioles
complete their
migration to the
poles
The
chromosomes
line up in the
middle of the cell
("the equator")

Anaphase

Spindles attached to
kinetochores begin to
shorten.
This exerts a force on the
sister chromatids that pulls
them apart.
Spindle fibers continue to
shorten, pulling
chromatids to opposite
poles.
This ensures that each
daughter cell gets identical
sets of chromosomes

Telophase
The chromosomes
decondense
The nuclear
envelope forms
Cytokinesis
reaches
completion,
creating two
daughter cells

MEIOSIS
A division of the nucleus that
reduces chromosome number by
half.
Important in sexual reproduction
Involves combining the genetic
information of one parent with that
of the other parent to produce a
genetically distinct individual

REMEMBER!

Synapsis - pairing of
homologous chromosomes
forming a tetrad.
Crossing over - chromatids of
tetrad exchange parts.

Phases of Meiosis

A diploid cell replicates its


chromosomes
Two stages of meiosis

Meiosis I and Meiosis II

Only 1 replication

Prophase I
Chromosomes
condense
Homologous
chromosomes pair w/
each other
Each pair contains
four sister
chromatids tetrad
(crossing-over)

Metaphase I

Tetrads or
homologous
chromosome
s move to
center of
cell

Anaphase I

Homologou
s
chromosom
es pulled to
opposite
poles

Telophase I
Daughter
nuclei
formed
These are
haploid
(1n)

Meiosis II
Daughter cells undergo
a second division; much
like mitosis
NO ADDITIONAL
REPLICATION OCCURS

Prophase II

Spindle
fibers form
again

Metaphase II

Sister
chromatids
move to the
center

Anaphase II
Centromeres
split
Individual
chromosomes
are pulled to
poles

Telophase II &
Cytokinesis

Four
haploid
daughter
cells
results
from one
original
diploid cell

Comparison

MITOSIS

MEIOSIS

MOLECULA
R
GENETICS

Genetic code
a.
b.
c.
d.

Genetic codes
Transcription
Translation
Replication

DNA (Deoxyribonucleic Acid)

Genetic material of
cells

GENES units of genetic material


that CODES FOR A SPECIFIC TRAIT
Called NUCLEIC ACIDS
DNA is made up of repeating
molecules called NUCLEOTIDES

DNA Nucleotide
Phosphate
Group

O
O=P-O
O

CH2
O
N
Nitrogenous base
C
(A, G, C, or T)
1

C4
Sugar
(deoxyribose)

C3

C2

HISTORY OF DNA
Discovery of the DNA double
helix

1928 - Frederick Griffith


Discovers that a factor in diseased
bacteria can transform harmless
bacteria into deadly bacteria
1952 - Rosalind Franklin - X-ray
photo of DNA.
1953 - Watson and Crick described the DNA molecule from
Franklins X-ray.

Watson & Crick


proposed
DNA had specific pairing
between the nitrogen bases:
ADENINE THYMINE
CYTOSINE GUANINE
DNA was made of 2 long stands
of nucleotides arranged in a
specific way called the
Complementary Rule

DNA Double Helix

Rungs of ladder
Nitrogenous
Base (A,T,G or C)

Legs of ladder

Phosphate &
Sugar Backbone

DNA Double Helix


Structure
O
5

P
5

O
O

4
2

O
O

Nitrogenous Bases

PURINES
1. Adenine (A)
2. Guanine (G)

A or G

PYRIMIDINES
3. Thymine (T)
4. Cytosine (C)

T or C

Chargaffs Rule

Adenine must pair with Thymine

Guanine must pair with Cytosine

Their amounts in a given DNA molecule


will be about the same.

BASE-PAIRINGS
H-bonds

Genetic Diversity

Different arrangements of
NUCLEOTIDES in a nucleic
acid (DNA) provides the key
to DIVERSITY among living
organisms.

The Code of Life

The code of the


chromosome is the
SPECIFIC ORDER that
bases occur.
A T C G T A T G C G G

DNA is
wrapped
tightly
around
histones
and coiled
tightly to
form
chromosom
es

DNA REPLICATION, Translation and


transcription

Replication, Transcription, and Translation

Before a cell can divide, the DNA in the


nucleus of the cell must be duplicated.

Since the DNA molecule consists of two


complimentary stands, if those two strands
separate and the right conditions are
present, two new stands that are the
compliments of the originals will be
produced.

Each new DNA molecule will consist of


one old stand, and a new complimentary
strand.

The gray strands in the figure to the right


are new strands in the process of being
assembled.

Assembling the New Bases

The term semiconservative replication means that in the


new DNA molecule there is one old and one new strand.

This is seen in the figure below.

DNA Replication

Since the DNA molecule is very


large, there must be a way to
copy it faster than just
unwinding from one end to the
other!

This happens when the DNA


molecule separates at many
sites, forming thousands of
replication bubbles. This allows
parts of the DNA message to be
replicated simultaneously in
many locations.

DNA polymerase adds new


nucleotides , while DNA ligase
joints the DNA segments
together.

Why the fuss about DNA replication??

The process of DNA replication involves a number of enzymes


and proteins, and it a bit more complicated than seen in the
previous slide.

The important idea is that an exact duplication of the DNA


message is required, so that each new cell in the body has the
same set of genetic instructions as the cells that preceded it.

This also insures that every new generation of individuals has the
same genetic information as his/her parents.

DNA carries information that can be used to


construct the proteins which form structures
and regulate the bodys activities.

Protein synthesis involves two processes: transcription and


translation.

In transcription the DNA message is converted into an RNA


molecule.

In translation the RNA message is used to assemble amino


acids into a protein chain.

Times, They are a changing

For many years biologists referred to the one gene-one enzyme


hypothesis. It was believed that each gene controlled the
production of a single protein.

This was changed to the one gene-one protein hypothesis


because many proteins are structural proteins, not enzymes.

Since some proteins consist of several polypeptide chains that


are linked together, the hypothesis was changed again. This time
one gene-one polypeptide seemed more accurate.

As a result of the Human Genome Project, the one gene-one


polypeptide hypothesis has had to be changed again! We now
know that a gene can produce more than one polypeptide
depending upon how the information in the gene is read. More
about this later!

The genetic code

The genetic code is written in


the sequence of the 4 bases
of DNA: A, T, C, and G.

Three bases read in sequence


specify one of the 20 amino
acids found in protein
molecules.

A codon is the 3-base


sequence for an amino acid.

The message in the DNA is


transcribed into an RNA
molecule, and then translated
into a polypeptide

The Genetic Code II

There are 64 (4X4X4)


possible triplet codes, but
only 20 amino acids.

As seen in the table, more


than 1 triplet may code for
the same amino acid. This is
no problem, as long as no
triplet can code for more than
one amino acid.

Note that several codons can


also act as start (AUG) or stop
(UAA) signals.

Why do we need RNA too?

There are three types of RNA produced in the nucleus: mRNA,


tRNA, rRNA.

Messenger RNA (mRNA) is a copy of the DNA that codes for a


polypeptide.

When the two DNA strands of a gene separate, one of the strands
is transcribed into an RNA molecule with the aid of the enzyme
RNA polymerase.

The RNA strand elongates until it reaches a termination signal (a


sequence of bases in the DNA strand). At this time the RNA
molecule is released from the DNA, allowing the DNA strands to
reunite.

After production the RNA molecules leave the nucleus and enter

Cleaning up the Message

When the genetic message is


copied to make mRNA, the
message contains unwanted
base sequences.

The junk sequences (called


introns) are removed from the
message and the remaining
sequences (exons) are linked
together to produce a
sequence of codons that will
translate into a polypeptide.

This process occurs before


the message leaves the
nucleus.

Where oh where can the amino acids


be?

A second type of RNA is


transfer RNA, whose function
is to attach to a specific
amino acid and bring that
amino acids to the site where
polypeptides are being
constructed.
This RNA strand is twisted
and bonded into the shape
seen on the right.
One end of the molecule
attached to a specific amino
acid.
The other end has an exposed
sequence of 3-bases. These
are called the anticodon.
How many kinds of tRNA
must there be?

REMEMBER!

If you said 20 types of tRNA you are wrong!

There must be a different tRNA molecule for each of the


possible
triplets. This means 64 anticodons.
The anticodons of the tRNAs each have a complimentary
codon in the mRNA. For example the codon AUG would be
the compliment of the anticodon UAC.

The Role of Ribosomes

The third type of RNA is


risosomal RNA (rRNA).

Ribosomes are the decoding


units of the cell.

Each ribosome consists of two


subunits, and is an
assemblage of rRNA and
proteins.

Ribosomes have binding sites


for both tRNA and mRNA
molecules.

Reading the Message

An mRNA molecule attaches


to a ribosome.
As the ribosome moves along
the mRNA, 3-base codons are
exposed one at a time.
A tRNA with an anticodon that
is complimentary to the
codon of the mRNA
temporarily bonds with the
mRNA.
The ribosome positions the
molecules so that this
bonding occurs.
As the ribosome continues its
journey along the mRNA
additional tRNAs bring their
a.a. to the site of peptide
synthesis.

Elongation of the chain

As new amino acids are


brought to the ribosome, the
growing peptide chain is
attached to the new amino
acid by a peptide bond.

Elongation of the chain


continues until a stop codon
is encountered. At that point
the peptide chain is released
from the tRNA.

A single mRNA can be read


repeatedly to make many
copies of a polypeptide.

Once a tRNA gives up its


amino acid it can return to
the cytoplasm and attach to
another of its specified amino
acid.

A Summary of the flow of Genetic


Information in a Cell

Information is stored in the


triplet codes (codons) of
DNA nucleotides.

This information is
transcribed into 3 types of
RNA.

mRNA carries the


information to assemble a
polypeptide.

In the nucleus, introns are


removed and the
remaining exons spliced
together to make a
functional mRNA strand.

tRNA molecules attach to


specific amino acids.

rRNA and proteins form


ribosomes.

mRNA attaches to a
ribosome and the message
is decoded when the
anticodon of a tRNA is
bonded to a mRNA codon.

Subsequent amino acids


are attached to the
growing peptide chain until
a stop codon is reach and
the chain is terminated.

A summary of these
events can be seen in the
next slide.

Mutation: When the Code is Miscopied

A mutation occurs when


the code doesnt copy
correctly, and a protein is
formed that doesnt
function.
If a base is substituted or
deleted, the triplet(s) are
different and so is the
protein formed.
Mutations can also
involved inversion or
deletion of larger sections
of the message.
Substances that trigger
mutations are called
mutagens and can be
physical or chemical in
nature.

DNA REPAIR

MECHANISMS OF DNA
REPAIR
PROOF READING ABILITY OF
DNA POLYMERASES
most important mechanism for
correcting DNA replication errors.

MISMATCH REPAIR
second type of editing where
an incorrect nucleotide is removed and
the corrected one is inserted in its plate

Factors that alter DNA:


a.

Alkylating agents
- react with guanine, results in depurination

b.

Cancer treatments

- puts cancer cells at greater risk for cell death than normal
cells
c.

Ionizing radiation and Strong oxidants


- i.e peroxides, cause single- strand breaks

d.

UV radiation
- alter thymine bases

e.

Certain drugs such as Antibiotic


Mitomycin C

Major DNA repair systems:


a.

Photoreactivation

b.

Excision repair (a.k.a cut & patch repair)

c.

Uses the correct DNA strand to fill in the strand where the error
is deleted

Mismatch repair

e.

disrupted section of DNA is removed, and a newly formed DNA


segment is ligated into place

Recombinational repair

d.

Exposure to UV light, activates photoreactivation enzyme

Able to remove the incorrect nucleotides and insert the correct


ones

SOS repair

Repair the damaged DNA through recombination events that


remove the damaged sections & replace them with the correct
sequences

Mutations

REMEMBER!
Mutation - any change in the
structure or sequence of DNA,
whether physical or biochemical
Mutant - an organism which DNA
sequence is different from that of
the parent organism
Wild type - an organism with
original form of DNA sequence
Mutagens- chemicals and
conditions that may cause

Different types of
Mutations
POINT MUTATION
- simplest; one nucleotide in the
sequence is changed
A.

Different types of
Mutations
SILENT MUTATION
- no effect on the amino acid because of
its redundancy
C. TRANSITION
- transition in which 1 purine is
substituted for another purine, or 1
pyrimidine is substituted for another
pyrimidine
D. TRANSVERSION
- a purine is substituted for a pyrimidine
or a pyrimidine for a purine
B.

Different types of
Mutations
E.

MISSENSE POINT MUTATION


- deleterious effect on peptide
sequence; results change in a codon,
which alters the amino acid in the
corresponding peptide;
simply INCORRECT AMINO ACID

NONSENSE MUTATION
- amino acid codon results to any of the
STOP CODONS which are the UAG
(amber), UGA (opal), UAA (ochre)
F.

Different types of
Mutations
FRAMESHIFT MUTATION
- involves insertion or deletion of nucleotides that
may alter the reading frame
G.

DUPLICATION
- give rise to pseudogenes or junk DNA that does
not code for proteins
H.

(i.e: glycophorin A and B genes and genes RHD and RHCE)

DELETION
- not capable of being corrected by any DNA repair
systems due to the size and complexity of mutation
I.