BASIC GENETICS

Classic genetics
Based upon the understanding of the
biochemical and biophysical natur of
nucleic acids including DNA, RNA, and the
various proteins that are part of the
chromosomal architecture

 Based on cell division involving

chromosomes, which consist of units of
inheritance called genes. Somatic cells
containing 46 chromosomes (22 pairs of
automosomes and two sex chromosomes,
either XX or YY) divide by mitosis.

The genes on the chromosomes

obey Mendelian laws as follows:
Inheritance is based on "factors" (genes)
that are transmitted to offspring as discrete
units. For each trait a person has two
factors (alleles), one from each parent.
The two alleles always segregate and
pass to different gametes.
Factors for different traits assort to
gametes independently, i.e., maternal and
paternal genes randomly recombine in the
gametes

 The tenets of classical genetics can be

applied to the inheritance of blood group
genes. To illustrate, for the ABO blood
group system parents who
are AO and BO can produce offspring of
all ABO groups

Population
genetics
genetic structure of a population

Population
genetics
genetic structure of a population
group of individuals
of the same species
that can interbreed

Population
genetics
genetic structure of a population
alleles
genotypes

group of individuals
of the same species
that can interbreed

Patterns of genetic variation in populations

Changes in genetic structure through time

Describing genetic
genotype frequencies
structure
allele frequencies
rr = white
Rr = pink
RR = red

Describing genetic
structure

genotype frequencies
allele frequencies
200 white
500 pink

genotype
frequencies:
200/1000 = 0.2 rr
500/1000 = 0.5 Rr

300 red
total = 1000 flowers

300/1000 = 0.3 RR

Describing genetic
structure

genotype frequencies
allele frequencies
200 rr = 400 r
500 Rr = 500 r
= 500 R

allele
frequencies:
900/2000 = 0.45 r
1100/2000 = 0.55 R

300 RR= 600 R

total = 2000 alleles

for a
population
with
100 GG
genotypes:
160 Gg

140 gg

calculate:
Genotype frequencies

Phenotype frequencies

Allele frequencies

for a
population
with
100 GG
genotypes:
160 Gg

calculate:
Genotype frequencies

100/400
=
0.25
GG
260
0.65
160/400 = 0.40 Gg
140/400
=
0.35
gg
Phenotype frequencies

260/400 = 0.65 green

140/400 = 0.35 brown

140 gg

Allele frequencies

360/800 = 0.45 G
440/800 = 0.55 g

How does genetic structure

change?

How does genetic structure

change?
changes in allele frequencies
and/or genotype frequencies
through time

How does genetic structure

change?
changes in allele frequencies
and/or genotype frequencies
through time
mutation

migration
natural selection
genetic drift
non-random mating

How does genetic structure

mutation
change?

spontaneous change in DNA

migration

creates new alleles

natural selection

ultimate source of all

genetic variation

genetic drift
non-random mating

How does genetic structure

mutation
change?
migration

individuals move into populatio

natural selection introduces new alleles

genetic drift
non-random mating

gene flow

How does genetic structure

mutation
change?
migration

certain genotypes produce

more offspring

natural selection

differences in survival
or reproduction
differences infitness

genetic drift

leads to adaptation

non-random mating

How does genetic structure

mutation
change?
migration
genetic change by chance alone

natural selection
genetic drift

sampling error

misrepresentation
non-random mating small populations

How does genetic structure

mutation
change?
migration
natural selection
genetic drift
non-random mating

cause changes in
allele frequencies

How does genetic structure

change?
mutation
migration
natural selection
genetic drift

mating combines alleles

into genotypes
non-random mating

non-random mating

non-random
allele combinations

Mendels Laws of Heredity

Jam Figueroa

Mendels Laws of Heredity

GregorMendel,anAustrianmonk,in1865carriedout
importantstudiesofhereditythepassingonof
heredity
characteristicsfromparentstooffspring.
Mendelwasthefirstpersontosucceedinpredictinghow
traitsaretransferredfromonegenerationtothenext.
Traitscharacteristicsthatareinherited.
Traits
Acompleteexplanationrequiresthecarefulstudyof
geneticsthebranchofbiologythatstudiesheredity.
genetics

Mendels Laws of Heredity

Mendelstudiedgardenpeaplantsbecausetheyreproduce
sexually,whichmeansthattheyproducemaleandfemale
sexcells,calledgametes.
gametes
Themalegamete(sperm)forms
sperm
inthepollengrain,whichis
producedinthemale
reproductiveorgan.
Thefemalegamete(egg)forms
egg
inthefemalereproductive
organ.

Mendels Laws of Heredity

Inaprocesscalledfertilization,the
malegameteuniteswiththefemale
gamete.
Theresultingfertilizedcell,calledazygote,then
zygote
developsintoaseed.
Thetransferofpollengrainsfromamalereproductive
organtoafemalereproductiveorganinaplantis
calledpollination.
pollination

Mendels Experiments
Whenhewantedtobreed,orcross,
oneplantwithanother,Mendel
openedthepetalsofaflowerand
removedthemaleorgans

Mendels Experiments
Hethendustedthefemaleorganwithpollenfromtheplanthe
wishedtocrossitwith.
Crosspollination

Poll
en
grai
ns

Transfer
pollen

Fem

Mal

Mendels Experiments
Thisprocessiscalledcrosspollination.Byusingthis
technique,Mendelcouldbesureoftheparentsinhiscross.
Hestudiedonlyonetraitatatimetocontrolvariables,and
heanalyzedhisdatamathematically.
Thetallpeaplantsheworkedwithwerefrompopulations
ofplantsthathadbeentallformanygenerationsandhad
alwaysproducedtalloffspring.
Suchplantsaresaidtobetruebreedingfortallness.
Likewise,theshortplantsheworkedwithweretrue
breedingforshortness.

TheFirstGeneration(F1)

TheSecondGeneration(F2)
Mendelallowedthetallplantsinthisfirstgenerationto
selfpollinate.
Aftertheseedsformed,heplantedthemandcounted
morethan1000plantsinthissecondgeneration.
Threefourthsoftheplantswereastallasthetallplants
intheparentandfirstgenerations.
Onefourthoftheoffspringwereasshortastheshort
plantsintheparentgeneration.

TheSecondGeneration
Theoriginalparents,thetrue
breedingplants,areknownas
theP1generation.
Theoffspringoftheparent
plantsareknownastheF1
generation.

P1

Shortpeaplant

TheoffspringoftwoF1plants
crossedwitheachotherare
knownastheF2generation.

Tallpeaplant

F1

Alltallpeaplants
F2
3tall:1short

TheRuleofUnitFactors

TheRuleofDominance

Short plan

Tall plant

t t

TT

T
F
1
All tall plants

Tt

TheRuleofDominance
Whenrecordingtheresultsofcrosses,
itiscustomarytousethesameletter
fordifferentallelesofthesamegene.
Anuppercaseletterisusedforthe
dominantalleleandalowercaseletter
fortherecessiveallele.
Thedominantalleleisalwayswritten
first.

Short plan

Tall plant

t t

TT

T
F
1
All tall plants

Tt

Dominant and Recessive Alleles in Pea

Plants
Seed
shape

Seed

color

round

yellow

Flower

color

Flower
position

Pod

color

Pod

shape

Plant

height

inflated

Dominant

Traits
purple

axial
(side)

green

Recessive

Traits
wrinkled

green

white

terminal
(tips)

yellow

constricted

t
a
l
l

short

TheRuleofDominance

TheRuleofDominance
Anuppercaseletterisusedfor
thedominantalleleanda
lowercaseletterforthe
recessiveallele.
Thedominantalleleisalways
writtenfirst.

Short
plant

Tall plant

tt

TT

T
F
1

All tall plants

Tt

TheLawofSegregation
Thelawofsegregationstatesthatevery
individualhastwoallelesofeachgeneand
whengametesareproduced,eachgamete
receivesoneofthesealleles.
Duringfertilization,thesegametesrandomly
pairtoproducefourcombinationsofalleles.

PhenotypesandGenotypes

PhenotypesandGenotypes
Tt Ttcross

Twoorganismscan
F1
lookalikebuthave
different
Tallplant
Tallplant
T t
T t
underlyingallele
combinations.
F2

TT
a

Tt
a

Tt
a

Sh
t t
o

TheLawofIndependentAssortment
Genesfordifferenttraitsareinherited
independentlyofeachother.
Example:seedshapeandseedcolor

PunnettSquares

HardyWeinberg
Principle

 In 1908, the English mathematician

G.H. Hardy and the German physician
W. Weinberg developed a
mathematical approach in which allele
frequencies, genotype frequencies and
phenotype frequencies could be used
to study the genetic composition of
population.
G.H. Hardy
mathematician

W. Weinberg
physician

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.

 If all of these criteria happen,

new alleles are not introduced
to a population and therefore,
the population isnt evolving.
This doesnt happen in reality
but the rate these change has
a direct affect on the rate of
evolution.

A general formula is used to represent the relative

frequencies of alleles of a single gene within a
population:

p + q = 1

where:
p = the relative frequency of the dominant
allele and
q = the relative frequency of the recessive
allele

Hardy-Weinberg Equation

p + 2pq + q =
1
2

p2 = relative frequency of homozygous dominants (e.g.,

BB)
2pq = relative frequency of heterozygotes (e.g., Bb)
q2 = relative frequency of homozygous recessives (e.g.,
bb)

BB

Bb

bb

p2 + 2pq + q2 = 1

H-W formulas
Alleles:

p+q=1

B
Genotypes:

p2 + 2pq + q2 = 1

BB
BB

Bb
Bb

bb
bb

Using Hardy-Weinberg equation

population:
100 cats
84 black, 16 white
How many of each
genotype?

BB

First calculate
frequency of b
from the known
number of bb
genotypes.

Bb

bb

Using Hardy-Weinberg equation

population:
100 cats
84 black, 16 white
How many of each
allele?

BB

q2 (bb)= 16/100 = .16

q (b): .16 = 0.4
Now work out p
p (B)= 1 - 0.4 = 0.6

Bb

bb

Using Hardy-Weinberg equation

population:
100 cats
84 black, 16 white
How many of each genotype?

p2 + 2pq + q2 = 1
p2=0.36
BB

2pq=0.48
Bb

q2=0.16

bb

q2 (bb): 16/100 =
0.16
q (b): .16 = 0.4
p (B): 1 - 0.4 = 0.6
2pq = 2 x 0.6 x
0.4 = 0.48

Why do we have to start the problem with

the percentage of the homozygous
recessive in the population?

Answer : It is not possible to tell

the homozygous dominant (AA)
from the heterozygous (Aa) by
examining the phenotype!

INHERITANCE
PATTERNS

Pedigree Analysis
A pedigree is a family tree that describes
the interrelationships of parents and children
across generations
Inheritance patterns of particular traits can
be traced and described using pedigrees

SCHEMATIC ILLUSTRATION OF
COMMONINHERITANCE PATTERN
MALES represented by squares
FEMALES represented by circles
MATING a line joining a male and
female
OFFSPRING indicates a vertical line
CONSANGUINEOUS MATING a
double line between male and female

 STILL BIRTH OR ABORTION indicated by small black circle

DECEASED FAMILY MEMEBERS a line crossed through
them
PROPOSITUS indicate by an arrow appointing to it; indicates
the most interesting or important member of the pedigree
Something unusual about the propositus is often the reason the
pedigree analysis is undertaken

TYPES OF INHERITANCE PATTERNS:

1.) Autosomal recessive
-It is a trait manifested by people who are
homozygous for the alleles. Both parents who
do not express the trait maybe carrier or
heterozygous for the recessive allele.
Example:
dd genotype, Bombay phenotype
Autosomal- refers to traits that are not carried on the sex
chromosomes
Recessive- trait is carried by either parent or both parents but is not
generally seen at the phenotypic level unless both parent carry the
trait

2.) Autosomal dominant

- It is a trait that appears when the gene that has
been inherited can be found in each generation
and occurs with equal frequency in males and
females.
Example:
(Lu) suppressor gene

2.) X-linked dominant

- it is a trait transmitted to all daughters
of affected father but not to sons.

Example:
Xga blood group system
- one of the blood group systems that follow an X-linked
inheritance patterns

3.) X- linked recessive

-

The traits appear much more frequently in males than in

females due to inheritance from carrier mothers

Example:
Hemophilia A

LOVE YOUR FAMILY

Cont. Cellular Genetics

It takes 2 gametes to make a fertilized egg
with the correct number (2N) number of
chromosomes in the nucleus of a cell.
Each parent gives only half (1N).
Genes composed of discrete units of DNA
arranged in a linear fashion, similar to strand
of pearls, with structural proteins wrapped
around the DNA at specific intervals to pack it
into tightly wound bundles.
The specific sequence of nucleotides and the
location on the chromosomes determines a
gene.

 At each locus (plural= loci) there may be only one

or several different forms of the gene, which are
called alleles.
Genotype is the sequence of DNA that is inherited.
Phenotype is anything that is produced by the
genotype.
Ex. Enzyme to control a blood group Ag, length of long
bones, curvature of spine, eye, skin, hair color and etc..

 Depending on the alleles inherited, an organism

can either be homozygous or heterozygous for a
specific trait.
Amorph silent gene, is a gene that does not
produce any obvious, easily detectable traits and is
seen only at the phenotypic level when the
individual is homozygous for the trait.
Hemizygous refers to the condition when one
chromosome has a copy of the geneand the other
chromosome has that gene deleted or absent.

Mitosis and Meiosis

Ainnah Marielle O. Torres
BSMT 4-2

Mitosis

Interphase
Prophase
Metaphase
Anaphase
Telophase

Mitosis
Interphase (2N) - Resting stage between cell
division; during this period , cell are synthesizing
RNA and proteins, and chromatin is uncondensed.
Prophase (4N) 1st stage of mitotic cell division.
Chromosomes become visible and condense.
Each chromosome has two chromatids from
duplication of DNA, and chromatids are linked via
the centromeres.
Metaphase (4N) Chromosomes move toward
the equator of the cell and are held in place by
microtubules attached at the mitotic spindle
apparatus.

Mitosis
Anaphase (4N) The two sister chromatids
separate. Each one migrates to opposite poles of
the cell, and the diameter of the cell decreases at
equator.
Telophase (2N) Chromosomes are at the poles
of the cell, and the cell membrane divides between
the two nuclei. The cell divides, and each cell
contains a pair of chromosomes identical to the
parent cell.

Meiosis

Interphase
Prophase 1
Metaphase 1
Anaphase 1
Telophase 1
Metaphase 2
Anaphase 2
Telophase 2

Meiosis

Meiosis
Interphase (2N) Resting stage between cell divisions;
during this period, cells are synthesizing RNA and
proteins, and chromatin is uncondensed.
Prophase 1 (4N) First stage of meiotic division.
Chromosomes condense. Homologous chromosomes
pair to become bivalent. Chromosome crossing over
occurs at this stage.
Metaphase 1 (4N) Bivalent chromosomes align at cell
equator. Bivalent chromosomes contain all four of the
cells copies of each chromosome.

Meiosis
Anaphase 1 (4N) Homologous pairs move to
opposite poles of the cell. The two sister chromatids
separate.
Telophase 1 (2N) The cell separates to become two
daughter cells. The new cells are now 2N.
Metaphase 2 (2N) homologoues line up at the
equator.
Anaphase 2 (N) Homologues move to opposite poles
of the cell equator.
Telophase 2 (N) Each cell separates into two new
cells. There are now 4 (N) cells with a unique genetic
cionstitution.

The Generative Cell Cycle

Stage

Description

Configuration

G0 (Gap 0)

Temporary resting
period
No cell division

2N

G1 (Gap 1)

Cells produce RNA

and synthesize
protein

2N

S (Synthesis)

DNA replication
occurs

4N

G2 (Gap 2)

During the gap

between DNA
synthesis and
Mitosis, the cell
continues to

4N

Genetic code

key according to which

sequence of sets of three
DNA nucleotides within a
gene is transcribed into a
sequence of sets of three
nucleotides within mRNA
(codon) and then translated
into
amino
acids,
the
building blocks of a peptide
or protein.

DNA
(Deoxyribonucleic
acid)
-backbone of heredity
-nucleic acid
-helical
-double stranded (antiparallel, _______)

-composed of 4 nitrogenous
bases:A, G, C,
T sugar
, 5-C
molecule (also called
___________), and a
phosphate group.
*sugar and phosphate moieties
comprises the backbone of the
DNA
-Purine:______ and _______
-Pyrimidine:_______ and
________

-codon
1. Start codon
2. Stop codon

-aka copying of DNA

-Complex process involving
numerous enzymes, nucleic
acid primers, various small
molecules, and the DNA helix
molecule.
-DNA must be copied before
___________ can occur and
must be copied with the same
number and sequence of DNA
for each daughter cells.

Steps:

1.DNA must be uncoiled by

____________ and
____________
2. Separation of two strands
done by __________ and
__________
3. Synthesis of a new strand in
the 5' to 3' direction on the
leading strand done by
___________________

4. Pairing of the newly

synthesized DNA strand with
one of the parent strand
5. Annealing
6. Joining the phosphodiester
bonds of DNA backbone to
complete the intact molecule
done by _____________

7. Recoiling of the DNA by

_______________
8. DNA is proofread by
proofreading enzymes
ex. ________________
*Okazaki fragment-joined by
________________ and
________________
9. Cell can continue with
mitosis

Note:
Nearly all DNA replication
is done in a
_______________ manner
and is
_________________ in
nature.

Genetic Code: RNA

Ribonucleic acid (RNA)

Is similar to DNA in structure but has certain key
differences.
A single stranded structure.
Uracil replaced thymine.
Uracil is similar to thymine but lacks methyl
group.

TYPES OF RNA
Ribosomal RNA (rRNA)- most abundant
and consistent.
Messenger RNA (mRNA)- encodes
specific genes.
Transfer RNA (tRNA)- bringing amino
acids to mRNA bound on the ribosome.
Small RNA molecules with various
functions.

TRANSCRIPTION
Is the cellular process by which DNA is
copied into the RNA.
Eukaryotic mRNA is modified after it is
made by various processing steps, such
as the removal of introns and addition of a
poly-A-tail to the 3 end.
These process takes place in the nucleus.

 Exons- coding region

Introns- noncoding region
RNA splicing- process by which introns are removed
from mRNA

TRANSLATION
Is the cellular process by which RNA
transcripts and turned into proteins and
peptides.
Occurs on the ribosome, and additional
steps may be necessary to get a specific
protein into its final correct form.
Proteins are made u[ of strings of amino
acids.

DNA Repair System

DNA Repair?
Genetic information carrier
Most important biomolecule in the cell
Essential to certain genetic information
unchanged
Chance to DNA damage is very high in cell
Human loses approx. 5000 everyday
DNA replication errors
DNA recombination errors
DNA damage in somatic cells cancer (loss of
gene function; damage in gametes transferred
to progeny
Damage to DNA major threat in all organisms
Cells has methods to overcome and rectify DNA
damage DNA Repair Mechanism

 It is essential for ultimate survival

Mechanistic Studies of DNA Repair Thomas
Lindahl, Paul Modrich, and Aziz Sancar (helps to
develop cancer therapeutics)
Destructive faces faced by DNA in the cells:
TWO CATEGORIES:
Internal (Intrinsic) metabolic intemediates,
reactive radicals, and DNA replication/recombination
errors

External (Extrinsic) radiations and

Carcinogenic chemicals/DNA intercalating
agents
All can create lesion in DNA
- pyrimidine dimer formation
- spontaneous depurination
- spontaneous deamination of bases
- errors in DNA replication

DNA Repair Mechanisms

Photoreactivation
Excision repair
Base excision repair & Nucleotide excision repair

Recombinational repair
homologous recombination & non-homologous endjoining

Mismatch repair
SOS response

Photoreactivation
Recovery by UV irradiated damage of
DNA by visible high
Cells recovers its DNA after UV
exposure
UV induces pyrimidine dimer
formation
First DNA repair mechanism
Proposed by Aziz Sancar

 Nucleotide excision repair

UV light chemicals

Damage base along with a short

strecth of healthy strand is removed
and later the gap with correct
nucleotides
Operated by cut and patch
Present in prokaryotes and eukaryotes
but mechanism and components
varies
Can remove a variety of bulky lesions
from DNA

Recombinational repair
Homologous recombination
Exchange of nucleotide sequences between two
similar or identical DNA molecules
In mitosis: repair doublestand breaks (DSB) DNA
repair
In meiosis: provide new combinations of DNA
sequences DNA mutation

It provides atransient physical link between

chromatids that promotes the orderly
segregation of chromosomes at the first
meiotic cell division

 Non-homologous end-joining
Complementary strand cannot exploited
because both strands are damage
No sister chromatids
Error prone mechanism
Imperfect repair
Better the leaving unrepaired

Mismatch repair
Replication errors
Corrects a single mismatch base pair
(C to A rather than T to A) or short
region of unpaired DNA
The defective region is recognized by
an endonuclease that makes a
single-strand cut at an adjacent
methylated GATC sequence
The DNA strand is removed through
the mutation, replaced, and religated

SOS response
Two regulatory proteins that control
SOS genes LexA and RecA protein
Synthesized at low background levels
LexA binds to the DNA region that
regulate the transcription of the
genes that are induced during the
SOS response
When the cells are exposed to UV
lights or other agents that cause DNA
damage, the RecA protein binds to
the ss region of DNA

DNA
MUTATIONS

DNA MUTATIONS
Mutation is any change in the
structure or sequence of DNA.

TYPES OF MUTATIONS:

POINT MUTATION:

1.
2.
3.

Missense mutation.
Silent mutation.
Non-sense mutation.

FRAME-SHIFT MUTATION:

1.
2.
3.

Insertion
Deletion
inversion

POINT MUTATIONS:
Point mutations are the singlebased mutations.

CLASSIFICATION OF POINT
MUTATION:
Missense
mutation
Silent mutation
Non-sense
mutation

MISSENSE MUTATION:
altering an amino acid of
polypeptide.
It can change the function of
polypeptide or not.

NON-SENSE MUTATION:
The new codon causes the protein
to prematurely TERMINATE,
producing a product that is
shortened and often does not
function.

SILENT MUTATION:
Silent mutation does not causes
any change
in amino acid.
(Silent mutation codes for same
amino acid)

FRAME-SHIFT MUTATION:

Frame-shift mutation is a change

in the reading frame of DNA.

+) Tay-Sacs Disease is caused by

frameshift mutation. It is lysosomal
storage disorder.

DELETION:

Mutations that result in MISSING

DNA are called DELETIONS.
Deletions can also cause frameshift mutation

For example:
ORIGINAL:

DELETION:

The fat cat ate

the wee rat

The fat ate the

wee rat

INSERTIONS:
Mutations that result in the
addition of extra DNA are called
insertions.
Insertions can also cause frame
shift mutations, and general
result in a nonfunctional protein.

For example:
ORIGINAL:

INSERTION:

The fat cat ate

the wee rat

The fat cat xlv

ate the wee rat

INVERSIONS:
In an inversion mutation, an entire
section of DNA is reversed.

inversions involve large regions

of a chromosome containing
several genes.

For example:
ORIGINAL:

INVERSION:

The fat cat ate

the wee rat

The fat tar eew

eht eta tac