1

Human and Population

Genetics
M. K. Tadjudin
Fakultas Kedokteran dan Ilmu Kesehatan
UIN Syarif Hidayatullah
2
Genetics
Mendelian Genetics Non-Mendelian Genetics
Cytoplasmic
inheritance
Polygenic
inheritance
Epigenetics
Dominance Co-dominance Epistasis
3
Gene
A discrete particle of inheritance
controlling a trait (pea shape or pea
appearance)
The segment of DNA involved in
producing polypetide chain (cistron). It
includes regions preceding and
following the coding region (leader and
trailer) as well as intervening sequences
(introns) between individual coding
segments (exons).
4
5
Allele = An alternative form of a
gene (R or r)
Phenotype = a trait exhibited by
an allele that distinguishes one
individual from another (round vs.
wrinkled)
Haplotype = particular
combination of alleles in a defined
region of a chromosome
P = G + E
6
7
Polymorphism
Simultaneous occurrence in the
population of genomes showing
variations at a given population
Polymorphism is present if the
frequency of an allele is > 1 %
8
9
Multiple alleles
Multiple alleles are different forms
of the same gene/locus
The sequence of the bases is
slightly different in the genes
located on the same place of the
chromosome
10
Polygenic traits
The result of the interaction
of several genes
11
Gametes ABC ABc AbC Abc aBC aBc abC abc
ABC 6 5 5 4 5 4 4 3
ABc 5 4 4 3 4 3 3 2
AbC 5 4 4 3 4 3 3 2
Abc 4 3 3 2 3 2 2 1
aBC 5 4 4 3 4 3 3 2
aBc 4 3 3 2 3 2 2 1
abC 4 3 3 2 3 2 2 1
abc 3 2 2 1 2 1 1 0
Polygenic inheritance
12
Pleiotropy
The effect of a single gene
on more than one
characteristic/effects
13
Disease risk
Prevention of
inherited traits:
Decision not to
reproduce
Fetal destruction
Abortion
Environmental
exposure
Genetic mutations
and polymorphisms
Reduction in
mutagens
Mutagens
Genetic
risks
Gene
therapy
To prevent
second hit
Environmental
risk
Radiation and
environmental
exposure:
Biological
Physical
Socioeconomic
Behavioral changes:
Smoking
Diet
Exercise
Drugs & alcohol
Other measures:
Chemoprevention
Early detection
Population
screening
Removal of target
organs

Disease
Inheritance
14
P = G + E
15
Definitions (1)
Population = all individuals of a
species
Mendelian Population = all
individuals of a species which can
interbreed within a defined
geographical boundary
16
Definitions (2)
Gene pool/gamete pool =
hypothetical mixture of genetic
units from which the next
generation will arise
Gene frequency= proportion of an
allele in a population
17
Population
Interbreeding groups of
organisms that are usually
subdivided into partially
isolated breeding groups
called demes or local
population
18
Study of human inheritance
Inborn characteristics of human
beings
Differences between human and non-
human beings
Characteristics of certain human
populations
Man is not an ideal species for the
study of genetics
19
20
21
22
Your ancestors
23
Eugenics
Eu =well; gen = grow;
eugenes = well born
Primary aim = to produce a
race of physically perfect
human beings
24
Positive eugenics
Attempts to increase
consistently better
germplasm and thus
preserve the best
germplasm of the society
25
Early marriage for those having desirable
traits
Subsidizing the fit
Gamete banks
Avoiding germinal wastage
Improvement of environmental condition
Genetic counseling
Promotion of genetic research
Positive eugenics
measures
26
Sexual separation of the defective
Sterilization
Control of immigration
Regulation of marriage
Negative eugenics
measures
27
A Nazi-era high-school
biology book warns
that "a hereditarily ill
person costs 50,000
reichsmarks on
average up to the age
of sixty." From the
U.S. Holocaust
Memorial Museum,
Washington, D.C.
30
The Nazi regime awarded
bronze medals to "fit"
Germanic women who had
four or five children, silver
medals to those who had
six or seven, and gold
medals to those with eight
or more. From the U.S.
Holocaust Memorial
Museum, Washington, D.C.
31
Euphenics
Symptomatic treatment of
genetic diseases:
Prevention
Replacement therapy
Research in human genetics
32
Mendelian population
Attributes:
Gene frequencies
Gene pool
33
Phenotype frequency
Genotype frequency
Gene frequency
34
Gene flow
New organisms entering a
population by migration and
mating in the new
population, thus bringing
new alleles to the local
gene pool
35
36
Genetic polymorphism
In a polymorphic locus the
frequency of a second allele >
1 %
39 % of loci are polymorphic
12 % of loci are heterozygous
Polymorphism is maintained by
heterozygous advantage
37
38
Hardy-Weinberg equilibrium
1. The allelic frequencies at an autosomal locus
in a population will not change from one
generation to the next (allelic frequency
equilibrium)
2. The genotypic frequencies of the population
are determined in a predictive way by the
allelic frequencies (genotypic frequency
equilibrium)
3. The equilibrium if perturbed will be
reestablished within one generation of
random mating at the new allelic frequencies
39
Assumptions of the Hardy-
Weinberg equilibrium
1. Random mating
2. Large and constant population size
3. No difference in fitness between the
different genotypes
4. No mutation
5. No migration
6. No natural selection/selection
40
41
Genotype TT
Freq. p x p = p
2

Gamete T
Freq. p
Gamete T
Freq. p
Gamete t
Freq. q
Gamete t
Freq. q
Genotype Tt
Freq. p x q = pq
Genotype Tt
Freq. p x q = pq
Genotype tt
Freq. q x q = q
2

Genotype frequencies of TT, Tt, and tt
TT = p
2
Tt = pq + pq = 2pq
tt = q
2

42
Mating frequencies
Genotype
Frequencies
TT
p
2

tt
q
2

Tt
2pq

F
e
m
a
l
e
s

TT
p
2

p
4

2p
3
q
p
2
q
2

Tt
2pq
2p
3
q
4p
2
q
2
2pq
3

tt
q
2

p
2
q
2
2pq
3

q
4

M a l e s
43
TT X TT
p
2
X p
2
=
p
4

p
4
- -
TT X Tt
(2)
2(p
2
X 2pq) =
4p
3
q
2p
3
q 2p
3
q
-
Mating
types
Mating
frequencies
TT Tt tt
TT X tt
(2)
2(p
2
X q
2
) =
2p
2
q
2

- 2p
2
q
2

-
Tt X Tt
2pq X 2pq =
4p
2
q
2

p
2
q
2
2p
2
q
2
p
2
q
2

Tt X tt
(2)
2(2pq X q
2
) =
4pq
3

- 2pq
3
2pq
3
tt X tt
q
2
X q
2
=
q
4

- - q
4
Frequency of offspring of different mating types
44
p
4
+ 4p
3
q + 6p
2
q
2
+ 4pq
3
+ q
4
=

p
2
(p
2
+ 2pq + q
2
) + 2pq(p
2
+ 2pq + q
2
)
+ q
2
(p
2
+ 2pq + q
2
) =
p
2
+ 2pq + q
2
= (p + q)
2
= 1
Total number of matings
45
TT: p
4
+ 2p
3
q + p
2
q
2
= p
2
(p
2
+ 2pq + q
2
) = p
2
(1) = p
2
Total frequency of offspring
Tt: 2p
3
q + 4p
2
q
2
+ 2pq
3
= 2pq(p
2
+ 2pq + q
2
) =
2pq (1) = 2pq
tt: p
2
q
2
+ 2pq
3
+ q
4
= q
2
(p
2
+ 2pq + q
2
) = q
2
(1) = q
2
46
Contributions of genes to
the next generation (1)
Parent population: [AA = 36] - [Aa = 39] - [aa = 25]
Total = 100

Number of genes in parent population:
A = (2 X 36) + (1 X 39) = 111
a = (1 X 39) + (2 X 25) = 89 = 0.45 = q
Total number of genes = 200

Gene frequencies in parent population:
A = 111/200 = 0.55 = p
a = 89/200 = 0.45 = q
47
Contributions of genes to
the next generation (2)
Genotype frequencies in the next
generation:

AA = (0.55)
2
= 0.3025

Aa = 2 X 0.55 X 0.45 = 0.495

aa = (0.45)
2
= 0.2025
48
H
2
=4DR

(2pq)
2
=4p
2
q
2

D = 10 = AA

H = 80 = Aa

R = 10 = aa

H
2
= 0.64

4 DR = 4 X 0.1 X 0.1 = 0.04 49
D = AA = 10
[A] = (2 X 10) + (1 X 80) = 100
H = Aa = 80
[a] = (2 X 10) + 1 X 80 = 100
R = aa = 10

Frekwensi gen [A] = 100/200 = 0.5 = p
Frekwensi gen [a] = 100/200 = 0.5= q
Frekwensi genotip [AA] = 0.5
2
= 0.25 = p
2

Frekwensi genotip [Aa] = 2 X 0.5

X 0.5 = 0.50 = 2pq
Frekwensi genotip [aa] = 0.5
2
= 0.25 = q
2
50
51
H- W Equilibrium in
X-linked genes (1)
In equilibrium gene frequencies in males and
females are the same
In a population: Males have 1/3 of all X-
chromosomes while females have 2/3
Gene frequency in males is the same as the
gene frequency in the mothers generation
Gene frequency in females =
2
mo fa p p
52
H- W Equilibrium in
X-linked genes (2)
Male genotypes:

X
H
Y = p

X
h
Y = q
Female genotypes:

X
H
X
H
= p
2

X
H
X
h
= 2pq


X
h
X
h
= q
2
53
H- W Equilibrium in
X-linked genes (3)
If the number of male = number of females,
then the gene frequency is:

p = 1/3 (p
males
) + 2/3 (p
females
) =





3
) 2 (
females males
p p
54
Males
0.2 0.5 0.35 0.425 0.3875

.40625

0.39675
Females
0.5 0.35 0.425 0.3875 0.40625 0.39675 0.401562
0 1 2 3 4 5 6
Generations
Zigzag change in gene frequencies
between males and females
55
X
H
Y p p
3
2p
2
q pq
2

X
h
Y q p
2
q 2pq
3
q
3
X
H
X
H
X
H
X
h
X
h
X
h

p
2
2pq q
2

Mothers genotype
Fathers
genotype
Freq
Mating frequencies of X-linked genes
56
Estimation of equilibrium
in dominance
Heterozygotes cannot be
distinguished from dominants
When recessive phenotypes are
rare carrier heterozygotes are
present in relatively high
frequency
Snyders ratio to check for H-W
equilibrium
57
p
2
AA p
4
2p
3
q p
2
q
2

2pqAa 2p
3
q 4p
2
q
2
2pq
3

q
2
aa p
2
q
2
2pq
3
q
4

p
2
AA 2pqAa q
2
aa
Dominant Recessive
Dominant
Recessive
Male
Parent
Female Parent
Snyders dominant ratio (1)
58
Snyders dominant ratio (2)
Proportion of recessive offspring in
dominant X dominant matings:
p
2
q
2

p
4
+ 4p
3
q + 4p
2
q
2

=
p
2
q
2

p
2
(p
2
+ 4pq + 4q
2
)

=
q
2

p
2
+ 4pq + 4q
2
=
q
2

[(p + q) + q]
2

q
2

(1 + q)
2

=
59
p
2
AA p
4
2p
3
q p
2
q
2

2pqAa 2p
3
q 4p
2
q
2
2pq
3

q
2
aa p
2
q
2
2pq
3
q
4

p
2
AA 2pqAa q
2
aa
Dominant Recessive
Dominant
Recessive
Male
Parent
Female Parent
Snyders recessive ratio (1)
60
Snyders recessive ratio (2)
Proportion of recessive offspring in
dominant X recessive matings:
2pq
3

2p
2
q
2
+ 4pq
3

=
2pq
3

2pq
2
(p + 2pq
3
)
= =
=
q
p + 2q
q
p + q + q
q
1 + q
61
Freq. of Non-
tasters among
offspring
Parents
Offspring
Mating
No.
Couples
Tasters
Non
Tasters
Total Obs. Exp.
Taster
X
Taster
425 929 130 1069 0.123 0.122
Taster
X Non-
Taster
289 483 278 761 0.365 0.349
Non-
Taster
X Non-
Taster
86 (5) 218 223
Total 800 1417 626 2043
Comparison of obs and exp freq of recessive phenotypes
SDR
SRR
PTC = PTU
Snyders experiment
62
Exp. SDR = = 0.537
2
/1.537
2
= 0.122
The frequency of the non-tasting allele is derived from
the frequency of homozyogous recessives among the
parents or [2 X number of recessive homozygotes(2R)]
+ [(number of heterozygotes(1H)] among (2 X number
of parents) = (2R + 1H)/2N = q
2


q =
Comparison of observed and expected
frequencies of recessive phenotypes
2R + 1H
2N
q = 461/1600 = 0.288 = 0.537
Exp. SRR = = 0.537/1.537 = 0.349
q
1 + q
q
2
(1 + q)
2

63
Freq. of Non-
tasters among
offspring
Parents
Offspring
Mating
No.
Couples
Tasters
Non
Tasters
Total Obs. Exp.
Taster
X
Taster
525 950 130 1080 0.12 0.12
Taster
X Non-
Taster
389 450 278 728 0.382 0.346
Non-
Taster
X Non-
Taster
86 0 218 218
Total 1000 1400 626 2026
Comparison of obs and exp freq of recessive phenotypes
SDR
SRR
PTC = PTU
TUGAS
64
H-W equilibrium in
multiple alleles (1)
The equilibrium condition is
described by the multinomial
expansion (p + q + r + )
2
If all the alleles are co-dominant
each genotype has its own distinct
phenotype and genotypic
frequencies can be easily scored
A
1
= p A
2
= q A
3
= r

A
1
A
1
A
1
A
2
A
1
A
3

A
2
A
2
A
2
A
3
A
3
A
3


p = (2 A
1
A
1
+ A
1
A
2
+ A
1
A
3
)/2N

q = (2 A
2
A
2
+ A
1
A
2
+ A
2
A
3
)/2N

r = (2 A
3
A
3
+ A
1
A
3
+ A
2
A
3
)/2N

65
66
H-W equilibrium in
multiple alleles (2)
Calculation of gene frequencies in co-dominance:
p =
2(A
1
A
1
) + (A
1
A
2
) + 2(A
1
A
3
)
2(A
2
A
2
) + (A
1
A
2
) + 2(A
2
A
3
)
2(A
3
A
3
) + (A
1
A
3
) + 2(A
2
A
3
)
q =
2N
2N
r =
2N
67
Genotype AA AO AB BB BO OO
Frequency p
2
2pr 2pq q
2
2qr r
2

Phenotypes
Human blood groups
In equilibrium frequency of B + O phenotypes =
q
2
+ 2qr + r
2
= (q + r)
2

As (p + q + r) = 1 1 (q + r) = p
So: 1 - (q + r)
2
= p - or: 1 - (B+O) phenotypes/N = p
Similarly 1 - (A+O) phenotypes/N = q
68
Genotype AA AO AB BB BO OO
Frequency p
2
2pr 2pq q
2
2qr r
2

280 13 19 288
In equilibrium frequency of B + O phenotypes =
q
2
+ 2qr + r
2
= (q + r)
2

As (p + q + r) = 1 1 (q + r) = p
So: 1 - (q + r)
2
= p - or: 1 - (B+O) phenotypes/N = p
Similarly 1 - (A+O) phenotypes/N = q
69
Observed
number
63 31 6 92 192
Phenotype
frequencies
0.3281 0.1615 0.0312 0.4792 1.000
Equilibrium
frequencies
(p
2
+2pr)N (q
2
+2qr)N (2pq)N (r
2
)N N
Expected
number
61 29 8 94 192

2
(with Yates
correction)
0.037 0.078 0.282 0.024 0.421
A B AB O Total
Phenotypes
Comparison of observed and expected frequencies
70
Phenoty-
pes
Number
observed
Frequency
SQRT of
frequency
Estimate
Correction
formula
Corrected
values
B + O 123 0.6407 0.8004
p =
0.1996
p(1+1/2d)
p =
0.2003
A + O 155 0.8703 0.8985
q =
0.1015
q(1+1/2d)
q =
0.1018
O 92 0.4792 0.6923
r =
0.6923
(r+1/2d) X
(1+1/2d)
r =
0.6979
370 0.9934
d =
0.0066
1.000
Bernsteins correction factor: d = 1 0.9934
Calculation of gene frequencies with Bernsteins correction
71
Observed
number
263 231 106 400 1000
Phenotype
frequencies
0.263 0.231
0.106=
2pq
0.4 = r
2
r=0.632
1
Equilibrium
frequencies
0.632
Expected
number
530 146 64 565

2
(with Yates
correction)
A B AB O Total
Phenotypes
TUGAS
72
Phenoty-
pes
Number
observed
Frequency
SQRT of
frequency
Estimate
Correction
formula
Corrected
values
B + O
231 +
400=631
0.631=
(q+r)
2

0.7944=
(q+r)
p= 1-(q+r)=
0.2056
p(1+1/2d)=
0.2056-0.0837
p = 0.1219
A + O
263 +
400=663
0.663=
(p+r)
2

0.8142
q=1-(p+r)=
0.1858
q(1+1/2d)=
0.1858-0.0837
q = 0.1021
O 400 0.4 0.6325 r = 0.6923
(r+1/2d) X
(1+1/2d)=
(0.6923-0.0837)x
(1-0.0837)
r = 0.5577
Yates
correcti
on
1000 1.0837
d=
-0.0837
0.7816
TUGAS
73
Assumptions of the Hardy-
Weinberg equilibrium
1. Random mating
2. Large and constant population size
3. No difference in fitness between the
different genotypes
4. No mutation
5. No migration
6. No natural selection/selection
74
Changes in gene frequencies
Mutation
Selection:
Gametic selection
Zygotic selection
Artificial selection
Natural selection
Migration
75
Mutation
The mere appearance of new genes
is no guarantee they will persist
A newly mutated gene has a very
small chance of survival
Size of offspring and mutation
rates influence chances for survival
of a newly mutated gene
76
# of
offsping/fam
0 1 2 3 4 5
Freq of fam e
-2
2e
-2
(2
2
/2! )
e-2
(2
3
/3! )
e-2
(2
4
/4! )
e-2
(2
5
/5! )
e-2
Prob of elim 1 1/2 ()
2
()
3
()
4
()
5
Freq of family
X prob of elim
e
-2
e
-2

(1/2!)e
-2
(1/3!)e
-2
(1/4!)e
-2
(1/5!)e
-2

Tot prob of
elim in 1
st
gen
e
-2
(1 + 1 + 1/2! + 1/3! + 1/4! + 1/5! + ) =
e
-2
(e) = e
-1
= 1/2.718 = 0.3679

Probability of elimination of mutant genes (1)
e = natural number = 2.303
77
Probability of elimination of mutant genes (2)
Probability of elimination in the 2
nd
generation =
e
-(1-0.3679)
= e
-0.6321
= 0.5315
Probability of elimination in the 3
rd
generation =
e
-(1-0.5315)
= e
-0.4685
= 0.6159
According to Fisher chances of a mutant gene
surviving after n generations = 2/n

The persistence and increase of many mutants
is due to recurrent mutations or the frequency
of mutations.
78
Mutation of A a - Forward mutation
Forward mutation rate = u
Mutation of a A - Backward mutation/
Reverse mutation
Reverse mutation rate = v
Mutation rate (1)
79
In equilibrium:
Forward mutation = Reverse mutation
up = vq

Since p = 1 q up = u(1 q)
So: u(1 q) = vq
u uq = vq
u = uq + vq = q(u + v)

q =
Mutation rate (2)
u
u + v
80
Selection (1)
Mechanisms for modifying the
reproductive success of a genotype
Artificial selection
Natural selection
Gametic selection
Zygotic selection
81
Selection (2)
FITNESS Relative reproductive
success Adaptive value -
Selective value
SELECTION COEFFICIENT (s):
The force acting on each
genotype to reduce its adaptive
value
82
Gametic selection (1)
Selection at the gamete level
As gametes are haploids the
gene frequency at the gamete
level = the gamete genotype
frequency
The rules for gametic selection
are also valid for haploid
organisms
83
Gametic selection (2)
Initial freq p
o
q
o
1
Fitness 1 1 s
After
selection
p q(1 s)
p + q sq
= 1 - sq
Gene freq
after sel.
p/(1 sq)
q(1 s)
(1 sq)

A a Total
Gamete genotypes
84
Change in gene frequency = q = q
1
q
o


= - q = - q


=


= =
Gametic selection (3)
q(1 s)
1 sq
(q sq)
1 sq
q sq q + sq
2

1 sq
sq + sq
2

1 sq
sq(1 q)q
1 sq
85
Gametic selection (4)
If s is small sq in the denominator can be ignored
sq = 0 and the denominator becomes = 1
The relationship for n generations calculated by
calculus is then:

sn = log
e
= 2.303 log
10



2.303 log
10

n =
q
0
(1 q
n
)
q
n
(1 q
0
)
q
0
(1 q
n
)
q
n
(1 q
0
)
q
0
(1 q
n
)
q
n
(1 q
0
)
s
86
Gametic selection (5)
If q
0
= 0.25 and s = 0.1, then the number of
generations (n) needed to reduce q
0
to q
n
= 0.10 is:


0.1n = 2.303 log
10



0.1n = 2.303 log
10


0.1n = 2.303 log
10
3 = 2.303(0.47712) = 1.09861

n = 1.09861/0.1 = 110 generations


0.25(1 0.10)
0.10(1 0.25)
0.25(0.90)
0.10(0.75)
87
Zygotic selection (1)
Initial
freq.
p
2
2pq q
2
1 q
Adaptive
value
1 1 1 s
Freq after
selection
p
2
2pq
q
2
(1 s)
(p
2
+2pq)=p
[p+(p+q)]=
p(1+q)

{ }=

=
Rel. freq.
=


=
0
AA Aa aa Total [a]
Genotypes
p
2

p(1 + q)
p
(1 + q)
2pq
p(1 + q)
2q
(1 + q)
2pq
p(1 + q)
pq
p(1 + q)
q
(1 + q)
s = 1
88
Zygotic selection (2)
q = - q = -
q
(1 + q)
q
(1 + q)
q(1 + q)
(1 + q)
= - = -
q
(1 + q)
q + q
2

(1 + q)
q
2

(1 + q)
Gene (a) is lethal in homozygous condition s = 1
89
Zygotic selection (3)
Initial
freq.
p
2
2pq q
2
1 q
Adaptive
value
1 1 1 s
Freq after
selection
p
2
2pq
q
2
(1 s)
(p
2
+2pq+q
2
)
-sq
2
=1-sq
2


=

=

=
Rel. freq.




AA Aa aa Total [a]
Genotypes
p
2

(1 sq
2
)
2pq
(1 sq
2
)
pq+q
2
(1-s)
1 sq
2
)
pq+q
2
-sq
1 sq
2

q(p+q-sq)
(1 sq
2
)
s < 1
q(1-sq)
(1 sq
2
)
q
2
( 1 s)
(1 sq
2
)
(1 sq
2
)
90
Zygotic selection (4)
q = - q = -
q(1-sq)
(1 sq
2
)
q(1-sq)
(1 sq
2
)
q(1-sq
2
)
(1 sq
2
)
= = =
q sq
2
q + sq
3

(1 sq
2
)
-sq
2
+ sq
3

(1 sq
2
)
Gene (a) is not lethal in homozygous condition s < 1
-sq
2
(1 q)
(1 sq
2
)
91
q
0
q
n
q
0
2
q
n
2

s=1 s=.80 s=.50 s=.10 s=.01 s=.001
.99 .75 .980 .562 1 5 8 38 382 3,820
.75 .50 .562 .250 1 2 3 18 176 1,765
.50 .25 .250 .062 2 4 6 31 310 3,099
.25 .10 .062 .010 6 9 14 71 710 7,099
.10 .01 .010 .0001 90 115 185 924 9,240
92,398
.01 .001 .0001
.0000
01
900 1,128 1,805 9,023
90,231 902,314
.001 .0001
.0000
01
.0000
0001
9,000
11,515 18,005 90,023 900,230 9,002,304
Change in
gene freq
Change in
freq of R
Number of generations necessary for
reaching new gene freq. at different
selection coefficients (s)
Generations necessary to reach a given change in
[q] of a deleterious recessive gene under different
selection coefficients
92
Selection against dominants(1)
Initial
freq.
p
2
2pq q
2
1 p
Adaptive
value
1 s 1 s 1
p
2
(1-s)+2pq(1-
s)+q
2
=p
2
-p
2
s+
2pq-2pqs+q
2
=
(p
2
+2pq+q
2
)-
p2s-2pqs=1-p2s-
2p(1-p)s=1-p
2
s-
2ps+2p
2
s=
1-sp(2-p)
Freq after
selection
p
2
(1-s)
2pq(1-s) q
2

Numerator = P
2
(1-s)+ pq(1-
s)=p
2
p
2
s+pq-pqs=p
2
-p
2
s+p(1-
p)-sp(1-p)=p
2
-p
2
s+p-p
2
-sp+sp
2
=
p sp

Rel. freq.


AA Aa aa Total [A]
Genotypes
p
2
(1-s)
1-sp(2-p)
2pq(1-s)
1-sp(2-p)
q
2

1-sp(2-p)
p sp
1 sp(2 p)
93
Selection against dominants (2)
p = - p =
p s p
1 sp(2-p)
= =


= =
p sp p + sp
2
(2 p)
1 sp(2 p)
Gene (A) is not lethal in homozygous condition s < 1
p s p p{1 sp(2 p)}
1 sp(2-p)
sp + 2sp
2
sp
3
)
1 sp(2 p)
sp (1 2p
2
+ p
2
)
1 sp(2 p)
sp (1 p)
2

1 sp(2 p)
94
Selection in no dominance (1)
Initial
freq.
p
2
2pq q
2
1 p
Adaptive
value
1 1 s 1 2s
p
2
-p
2
s+ 2pq-
2pqs+q
2
-
2sq
2
=
(p
2
+2pq+q
2
)-
2pqs-2sq
2
=1-
2sq(p+q)=1-
2sq
Freq after
selection
p
2
2pq(1-s) q
2
(1 2s)

+ =

=
Rel. freq.


AA Aa aa Total [A]
Genotypes
p
2

1-2sq
2pq(1-s)
1-2sq
q
2
(1-2s)
1-2sq
pq(1-s)
1-2sq
q
2
(1-2s)
1-2sq
pq(1-s)+q
2
-2q
2
s
1-2sq
q-sq(1+q)
1-2sq
95
Selection in no dominance (2)
q = - q = -
q sq(1+q)
1 2sq
= = =
Fitness of heterozygotes is exactly intermediate
between the two homozygotes
q sq(1+q)
1 2sq
q(1-2sq)
1 2sq
q sq- sq
2
-q+2sq
2

1 2sq
-sq + sq
2

1 2sq
-sq(1 q)


1 2sq
96
q
0
q
n
q
0
q
n
s=1 s=.80 s=.50 s=.10 s=.01 s=.001
.99 .75 .01 .25 3 4 7 35 350 1,496
.75 .50 .25 .50 1 1 2 11 110 1,099
.50 .25 .50 .75 1 1 2 11 110 1,099
.25 .10 .75 .90 1 1 2 11 110 1,099
.10 .01 .90 .99 2 3 5 24 240 2,398
.01 .001 .990 .999 2 3 5 23 231 2,314
.001 .0001 .999 .9999 2 3 5 23 230 2,304
Change in
gene freq
(del. allele)
Change in
freq of [a]
(fav. allele)
Number of generations necessary for
reaching new gene freq. at different
selection coefficients (s)
Generations necessary to reach a given change in
[q] under different selection coefficients in the
absence of dominance (co-dominance)
97
Heterozygous advantage (1)
Heterozygote has superior
reproductive fitness to both
homozygotes
Overdominance
Permit equilibrium with both
alleles remaining in the population,
provided the selection coefficients
remain constant balanced
polymorphism
98
Heterozygous advantage (2)
Equilibrium is achieved when ps = qt.

If so then: ps + qs = qt + qs
s(p + q) = q(s + t)

Since p + q = 1 q =
s
s + t
Also ps + pt = qt + pt p(s + t) = t (p + q)

Since p + q = 1 p =
t
s + t
99
Initial
freq.
p
2
2pq q
2
1 p
Adaptive
value
1 s 1 1 t
p
2
-p
2
s+ 2pq+
q
2
-q
2
t=
(p
2
+2pq+q
2
)-
p
2
s-q
2
t=
1-p
2
s-q
2
t
Freq after
selection
p
2(
1 s) 2pq q
2
(1 t)

=

= =
Rel. freq.


AA Aa aa Total [A]
Genotypes
p
2
(1-s)
1-p
2
s-q
2
t
2pq
1-p
2
s-q
2
t
pq+q
2
(1-t)
1-p
2
s-q
2
t
Heterozygous advantage (3)
q
2
(1-t)
1-p
2
s-q
2
t
pq+q
2
-qt
1-p
2
s-q
2
t
q{(p+q)-qt}
1-p
2
s-q
2
t
q(1-qt)
1-p
2
s-q
2
t
100
q = - q =


= = =
Heterozygous advantage (4)
q(1-qt)
1-p
2
s-q
2
t
q(1-qt) q(1-p
2
s-q
2
t)
1-p
2
s-q
2
t
q+q
2
tpq
2
t-q
2
t)
1-p
2
s-q
2
t
qpq
2
t
1-p
2
s-q
2
t
pq(psqt)
1-p
2
s-q
2
t
101
Equilibrium between
mutation and selection (1)
-sq
2
(1 q)
(1 sq
2
)
For a deleterious recessive gene the loss per generation =
In equilibrium the loss of (a) genes through selection is
exactly balanced by the gain of (a) genes through
mutation. The frequency of newly mutated (a) genes =
u X [A] or up or u(1 q).
If s is small the denominator can be considered = 1
102
Equilibrium between
mutation and selection (2)
Thus: sq
2
(1 q) = u(1 q)

sq
2
= u

q
2
= u/s
q = u/s

If s = 1 q = u or q
2
= u The frequency of
homozygous lethals at equilibrium = the frequency of
new genes introduced by mutation.
103
Equilibrium between
mutation and selection (3)
For a deleterious dominant gene the reduction p can be
simplified to sp(1 p)
2.
Since q = (1 p) the mutation
rate of the recessive allele to dominant = u(1 p).

Equilibrium occurs when:
sp(1 p)
2
= u(1 p)
p(1 p) = u/s

Since small values of p can usually be expected when
the dominant gene is selected against (1 p) = 1
At equilibrium p = u/s
104
Estimation of mutation rates
and equilibrium frequencies
In dominance: p = u/s u = ps

When dominance is lacking the reduction of gene
frequencies per generation for low values of q is very
close to sq(1 q). As the mutation rate = u(1 q)
The selection mutation equilibrium is:
sq(1 q) = u(1 q)

q = u/s
105
Migration (1)
Recipient population
q
0

Q
m
m = proportion of newly
introduced gene
Genes in population after
migration = q
0
(1 m) + mQ

Difference in gene frequency
after migration = (1 m)(q
0
Q)
Q
106
Migration (2)
Gen Hybrid Mig
Gene freq diff between
hybrids and migrants
0 q
0
Q q
0
Q
1
q
0
(1-m)+mQ=q
0
-mq+mQ
Q
q
1
-Q=q
0
-mq+mQ-Q
=(1-m)(q
0
-Q)
2
(q
0
-mq+mQ)(1-m)+mQ
Q
q
2
-Q=q
0
-2mq+m2q
0
-Q
=(1-m)
2
(q
0
-Q)
n
q
n-1
(1-m)+mQ
Q
q
n
-Q=(1-m)
n
(q
0
-Q)
107
Migration (3)
When after n generations the gene frequency in a
hybrid population becomes q
n,
then:
q
n
Q = (1 m)
n
(q
0
Q)

(1 m)
n
=

q
0
- Q
q
n
- Q
If:
q
n
= 0.446
Q = 0.028
q
0
= 0.630
n = 10
m = 0.036
108
Mahram

( 22 )

( 23 )
[ : 22 23 ]
109
Dan janganlah kamu menikahi perempuan-perempuan yang telah
dinikahi oleh ayahmu, kecuali (kejadian pada masa) yang telah
lampau. Sungguh, perbuatan itu sangat keji dan dibenci (oleh Allah)
dan seburuk-buruk jalan (yang ditempuh). Diharamkan atas kamu
(menikahi) ibu-ibumu, anak-anakmu yang perempuan, saudara-
saudaramu yang perempuan, saudara-saudara ayahmu yang
perempuan, saudara-saudara ibumu yang perempuan, anak-anak
perempuan dari saudara-saudaramu yang laki-laki, anak-anak
perempuan dari saudara-saudaramu yang perempuan, ibu-ibumu
yang menyusui kamu, saudara-saudara perempuanmu sesusuan, ibu-
ibu istrimu (mertua), anak-anak perempuan dari istrimu (anak tiri)
yang dalam pemeliharaanmu dari istri yang telah kamu campuri,
tetapi jika kamu belum campur dengan istrimu itu (dan sudah kamu
ceraikan), maka tidak berdosa kamu (menikahinya), (dan diharamkan
bagimu) istri-istri anak kandungmu (menantu), dan (diharamkan)
mengumpulkan (dalam pernikahan) dua perempuan yang bersaudara,
kecuali yang telah terjadi pada masa lampau. Sungguh, Allah Maha
Pengampun, Maha Penyayang. (An-nisa 22 23)
110
Ptolomeus V Cleopatra I
Ptolomeus VI Cleopatra II
Cleopatra II
Ptolomeus VIII
Cleopatra III
Ptolomeus X Cleopatra IV Ptolomeus IX Cleopatra V
Berenice III Ptolomeus XII
Cleopatra VI
Cleopatra VII
111
Inbreeding
Occurs when two genes in a zygote
are identical
The probability that two genes in a
hybrid are identical is given by the
inbreeding coefficient
Inbreeding coefficient: The
probability that two genes in a
zygote are identical
112
A
1
A
1
aa
aa A
1
a A
1
a A
2
a
A
1
a A
1
A
2
A
1
A
1
A
1
A
2
A
1
a
identical similar different
Combinations of alleles from first-cousin mating
1/2 1/2
1/2
1/2
1/2
4

[c] = 0.01 [C] = 0.99

Cc = 2pq = 2 x 0.99 x 0.01 = 0.0198

Cc X Cc 2pq x 2pq = 0.0198
2
=
0.00039204

cc = 0.25 x 0.00039204 = 0.00009801
113
114
Inbreeding coefficient (1)
Gives the extent of mating between relatives
Chances in a diploid population of two
identical gametes coming together is for any
generation = 1/2N probability of newly
arisen identical homozygotes = 1/2N
The probability of the remaining zygotes,
1 (1/2N), will have identical genes is the
inbreeding coefficient of the previous
generation
115
Inbreeding coefficient (2)
F
0
= 0

F
1
= 1/2N

F
2
= 1/2N + (1 1/2N)F
1


F
3
= 1/2N + (1 1/2N)F
2

F
n
= 1/2N + (1 1/2N)F
n-1

116
Panmictic index (1)
Panmictic index or outbred state
If F is the inbreeding or fixation
index, then 1 F is the panmictic
index = P
P is a measure of the relative
amount of random-mating
heterozygosity that is diminished
by inbreeding
117
Panmictic index (2)
F
n
= 1/2N + (1 1/2N)F
n-1


1 P
n
= 1/2N + (1 1/2N)(1 P
n-1
)

P
n
= -1 + 1/2N + 1 1/2N P
n-1
) + (1/2N)P
n-1


P
n
= P
n-1
+ (1/2N)P
n-1

P
n
= P
n-1
{1 + (1/2N)P
n-1
}


P
n
= P
n-1
{1 - (1/2N)P
n-1
}

P
n
= P
0
(1 - 1/2N)
n!

118
Inbreeding pedigrees (1)
V V
X Y
Z
Brother-sister
full-sib mating
1/2 1/2
1/2
2

119
Inbreeding pedigrees (2)
R S
U V
Z
First-cousin
mating
X Y
T W
1
2
3
4
5
6
F = ()
4
() + ()
4
()
120
Inbreeding pedigrees (3)
U
V
Z
X Y
W
1
2
3
5
4
6
U = ()
4
() = ()
5

V = ()
4
() = ()
5
W =

()
2
() = ()
3
Z = U + V + W
121
Effects of non-
random mating
Inbreeding ----->
Increased homozygosity
122
Effects of changes in
population size
Sampling error: The allelic
frequencies of a population
fluctuates from generation to
generation -----> GENETIC
DRIFT
In very small population ----->
FIXATION
123
AA X AA X = 1/16 1 0
(2) AA X Aa
2 X X =
0.75 0.25
(2) AA X aa 2 X X = 1/8 0.50 0.50
Aa X Aa X = 0.50 0.50
(2) Aa X aa 2 X X = 1/4 0.25 0.75
aa X aa X = 1/16 0 1
A a Probability Mating
Gene frequencies
in mating parents
Probabilities of mating combinations
124
Genetic drift
Measured mathematically by the
standard deviation of a proportion
= pq/2N
125