FACULTY OF

MEDICINE
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International

POPULATION
GENETIC
By: E. SURYADI
Fakultas Kedokteran
UGM

FACULTY OF
MEDICINE
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Population genetic is the study

of genes in population

Distance between a gene with population

The stage of human being as organism
1. Molecular: genetic material (DNA, RNA):
protein, lipid hydrocarbon, vitamin etc
2. Sub cellular: nucleus, mitochondria,
endoplasmic reticulum golgi apparatus etc.
3. Cellular : myocyt, leukocyt, fibroblast,
neuron, melanocyt etc
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4. Tissue: Epithelium, connective tissue, muscle

and neural tissue
5. Organ: Lung, lever, heart, nose, eye etc
6. Body system: Respiration, digestion,
reproductive, cardiovascular, musculo
skeletal
7. Individual: Fat, thin, high, small etc
8. Population( Community): Chinese, Japanese,
Indonesian etc (ethic group)
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PROBLEMS

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1. How can we determine the frequency of a

gene in a population?
2. What factors affect gene frequencies?
3. Why are some genes more common than
others?
4. How does natural selection and mutation
role in maintaining gene frequencies?
5. What can we do to influence our own
evolution?
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FACULTY OF
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Application the population

genetic study in medical

* Searching the frequency of a gene especially in

individual heterozygote for genes causing
recessively inherited diseases
1. That can useful to genetic counselor
2. May be correlate to epidemiology of disease
( Etiology, distribution and controlling)
3. To plan the genetic screening program
* Are these changes large enough to worry about?
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Basics of Hardy _
Weinberg Principle

Chromosome in somas cell are diploid

Genes are arranged in linier order on
chromosomes
At locus :D: with two allele D or d
In population, the relative proportion of
the different genotypes remain constant
from one generation to another
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FORMULA 1

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In a population in equilibrium the

frequency of disease caused by an
autosomal recessive gene is the square
of the frequency of the recessive gene
or
The frequency of a gene in the square
root of the frequency of the
homozygote for that gene
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Formula 2

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The frequency of the heterozygote for two alleles

is the frequency of one allele multiplied by the
frequency of other allele, times two

p2(AA) + 2 pq (Aa) + q2(aa) =1

p + q =1
p = Frequency of allele A
q = Frequency of allele a

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In practice, We measure the frequency of

the disease and take the square root of
this to estimate the gene frequency

For example
Frequency of albinism in population is
1/20000
1
1
Thus: Frequency a gene of albinism 2

20.000
140
Frequency of heterolygote = 2pq
p=12X

1
1

140
709

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Autosomal dominant

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In autosomal dominant disorder, if gen

frequency is low ( under 1/150)
So each of patient is regarded as
heterozygote
Patient population = p2 + 2pq

p2 very low
Thus sum patient ~ 2pq
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Frequencies for
multiple alleles

We will calculate start in gene frequency of gene

recessive
For example:
Blood A, B, O types of 173 students in genetics
laboratory classes we determined as follow.
O=78; B=17; AB=7; and A=71
78
0,67
Gene frequency of O =
173
Than calculate in gene frequency of A. we used
Hardy-Weinberg formula for two
Allele O and A. (p + q)2 = 1
p=

71
78

173 173

0,86 0,93

Gene frequency of A = 0,93 0,67 = 0,26

Gene frequency of B = 1 0,93 = 0,7

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Frequency for sex

linked alleles

Allele in the sex chromosomes occur in a

different frequency than those in autosomes
In male organism have heterogametic sex
determination
For females = p2 (AA) + 2pq (Aa) + q2 (aa)
For males = p (A) + q (a)
(only one x chromosome)
Estimates of p and q can be made from male
phenotypic classes
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Haemophilia A ( X-linked recessive )

In population :1 in 10.000 male
Gene frequency = male affected = 1/10.000
Carrier frequency = 2pq
=2 x p x 1/10.000
p~1
=1/5000
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Factors Altering the

Frequencies of Genes

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Selection
Mutation
Genetic Drift
Migration/Isolation
Miotik Drive
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Effects Selection

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Selection forces operate by increasing or

decreasing fitness.
Fitness is a measure of fertility and therefore of
the contribution made to the genes of the
succeeding generation.
As the number of offspring who reach the mean
age of which the parent reproduced, so that
infant death and stillbirths.
Selection may operate on a gene at any time
from conception into adult time.
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Frequency gene a (q1) after

selection.
q1= q(1-q) + q2(1-s) or (q-sq2)
1-sq2
1-sq2
sq2 is very small
q1= q-sq2
q1= q(1-sq)
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Mutation

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A change in the genetic constitution

Vice versus mutation
u
A
a
v

u : mutation rate from A genes to a gene

v : mutation rate from a genes to A gene

If before mutation, Allele A frequency is 1-q

and a allele a is q1.
Equilibrium frequency can form if:
u
(1-q)u = q v or q =
u+v

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The Balance Between

Mutation and Selection

The frequency of any given allele reflects a

balance between the rate at which alleles of
this kind are being removed from the
population by selection and rate at which new
ones are being created by mutation.
A very long time gradualy selection and
gradualy mutation -> evolution

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A dominant gene can be formulate

2m
x=
1-f
x = frequency of disease
m = mutation rates
f = fitness of mutant gene
For a recessive gene can be formulate as
m
x=
1-f

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exercise

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How many the frequency of disease?

Autosomal dominant
achondroplasia mr = 14, fitness =0,6
retinoblastoma mr = 20, fitness =0,7
Autosomal recessive
total color blindness mr= 28,fitness =0,9
phenylketonuria
mr =25,fitness =0,5
mr = mutation rates
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Genetic Drift

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Variation in gene frequency can result

from genetic drift.
Fluctuation in gene frequency can
result from small sample.
For infinitely large populations, change
fluctuation become negligible.
Genetic Drift: large population < small
population
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Migration/Isolation

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The significance of migration in changing

allele frequencies depends on the degree of
previous isolation of the sub population
involved.
The environment such as rivers and islands
can provide models to explain isolation.
In isolation can become intra specific gene
flow and inter specific hybridization.
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Gene flow

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Migration->new territories -> exchange of

genes between these population
For example : gene for blood group B

very high in Asia > 25% but gradually

decreases as one travels west ward
across Europe --- in France and British less
than 10%

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Meiotic Drive

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Allele frequencies in population can

influence by irregularity in the
mechanics of the meiotic divisions.
Meiotic drive in nature depends on the
extent and persistence of preferential
segregation at meiosis.
An event, which is largely unknown.
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Effect of mating pattern

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RANDOM MATING
Gene carried by an individual do not
influence his choice of mate. F.e. : ABO
blood group.
Gene carried by an individual can influence
his choice of mate. F.e.:intelligence, stature
-- > NOT RANDOM

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Assortative mating and

imbreeding

Prevented from marrying outside their

group. F.e. : religious, political, cultural,
geografical.
increase the proportion of homozygote in
the population.
Imbreeding as isolated

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Polymorphism

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A pupolation of two or more genetically

determined forms could not be maintained
by mutation alone
Unaffected heterozygotes is very large
compare ith number of affected
homozygotes.
Two types : Balanced polymorphism (BP)
and Transien polymorphism(TP)
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BP f.e. : the sikle cell gene in Africa

Frequency of heterozygotes increase
because individual carriers of he sickle cell
gene are more resistant to infection by
falciparum malaria than normal persons
TP f.e. : the thalassaemia gene
environment changes / controlling of malaria
disease - heterozygotes decrease
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Variables of frequency
gene
Technology

Fertility

Social
Politics
Order

Selection

Genetic Drift

Population
Genetic

Isolation

Migration

Mutation

Meiosis Drive

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Some the known

principles of genetics

1. The gene is the unit of inheritance.

2. Genes are arranged in linear order on
chromosomes.
3. Chromosomes are single unit in reproductive
cells.
4. Members of a pair of genes and
chromosomes segregate to different
reproductive cells.
5. Members of different gene pairs are assorted
independently with respect to those of other
gene pairs in the formation of eggs and
sperm.
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6. Genes are units of deoxyribose nucleid

acid (DNA) and are capable of
replication. They carry coded messages
that can be transcribed and translated
into polypeptides.
7. Mutation occurs in genes and
chromosomes.
8. Multiple genes control in the
inheritance of quantitative traits.
9. Genes in populations establish on
equilibrium
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Just as our present knowledge and practice of

medicine relies on a sophisticated knowledge of
human anatomy, physiology and biochemistry, so
will dealing with disease in the future demand a
detailed understanding of the molecular anatomy
physiology and biochemistry of human genome. We
shall have to have physicians who are as conversant
with the molecular anatomy of chromosomes and
genes as the cardiac surgeon is with the structure
and workings of heart and circulatory tree
Paul Berg, MD
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Nobel Lecture, 1981