Transcript Population Genetics The study of distribution of genes in

Prepared By:
Dr. Awatif Ali Alam
Population Genetics
The study of distribution of genes in
populations and of how these gene
frequencies are maintained or changed.
Historical Background
• Gregor John Mendel (1865):
origin of modern human genetics.
• Francis Galton and Colleagues:
Studied variations predisposing to
diseases.
• Foundation of human medical genetics
was laid down during the first decade of
this century.
Historical Background cont…
• Rediscovery of Mendel’s work at turn of
century.
• Karl Landsteiner’s discovery of ABO
blood group system in 1901.
• Archibald Garrod discovery of “Inborn
Errors in Metabolism” in 1907.
Impact of Genetic Disease
• Physicians paid little attention to genetics
during the first three decades of the
previous century.
• Was not considered an intrinsic part of
medicine.
• Hereditary conditions were rare or so
rarely recognized.
• Genetics was developed by Zoologists
and Botanists.
Probability
• Similarity between gene transmission and toss of a
coin.
• A child receives his genotype from two parents.
• The chance that a child, both of whose parents are
(Aa) will receive the (A) allele from each is
½x½=¼
• Applies to sex ratios in families.
• Probability has no memory.
• Binomial distribution approximately equal probability
of combination of two independent events.
For two-child families, the frequencies of different
possible combinations of P & q presented by the
binomial distribution of P & q:-
(P & q)2 = P2 + 2 pq + q2
Families of 2 boys = p2 = ½ + ½ = ¼
Families of 2 girls = q2 = ½ x ½ = ¼
Families of a boy and a girl = 2pq = 2 x ½ x ½ = ½
Note: Primary and Secondary sex ratios.
Hardy Weinberg Principle:
• Expounded in 1908.
• Frequency of a hereditary disorder is
independent of whether the disease is a
dominant or recessive one.
• The Cornerstone of population genetics.
Statement:
[(Neglecting mutation, selection, gene flow,
and genetic drift)] the gene frequency and
genotype frequencies remain constant from
generation to generation.
P+q=1
Importance of “H-W”
Formula:
• Determining gene frequencies when the
genotype incidence is known.
• Calculating the proportion of heterozygotes
when the frequency of the recessive
phenotype is known.
Importance of “H-W” Formula: cont…
• Example:- If the incidence of (PKU) is 1 in
10,000 live births, and it is a recessive condition
then:
q2 =
1/10,000 = 0.0001
q =
0.0001 = 0.01
• Where q is the gene frequency for PKU.
The frequency of heterozygotes is 2 pq as:
P+q=1
P = 1 – 0.01 = 0.99
2 pq = 2 (0.99 x 0.01) = about 1/50
Pedigree Patterns:
The chief method of genetic study in man.
DOMINANT CONDITION
I.
1
2
3
II.
AFFECTED
3
4
5
6
7
}
2
}
1
AFFECTED
8
Criteria for recognizing autosomal
dominant inheritance: (Cont…)
1. Patients are heterozygotes.
2. Patients have one affected parent.
3. Boys and girls are equally likely to be
affected.
Recessive Condition
RECESSIVE CONDITION
I.
1
2
3
II.
1
2
3
4
5
APPARENTLY NORMAL
6
7
8
AFFECTED
The criteria for recognizing autosomal
recessive inheritance are:-
1. Patients are homozygotes.
2. Patients are the children of apparently
normal parents who, are obligate
heterozygotes.
3. One quarter of the sibs of the proband
are affected.
4. Boys are affected as often as girls.
5. Affected people who marry normal people
will have apparently normal children.
X-Linked Inheritance
I.
II.
1
2
4
1
2
3
1
2
3
HEMIZYGOTE
AFFECTED
5
III.
HOMOZYGOTE
NORMAL
4
HEMIZYGOTE HETEROZYGOTE
AFFECTED
CARRIER
Criteria for recognizing X-linked
inheritance are:
1.
2.
3.
4.
Affected boys are hemizygous.
50% of daughters are carriers.
50% of sons are affected.
Affected fathers do not have affected
sons.
5. All daughters of affected fathers are
carriers.
Consanguinity:
• There is an above – average risk of producing
homozygous off springs for a certain
recessive gene.
• Risk increases with closeness of relationship of
the parents.
• If prevalent in a population can disturb “H-W”
equilibrium by increasing the proportion of
homozygotes at the expense of heterozygotes
“Genetic Isolates”.
Coefficient of in Breeding:
• Is the probability that an individual
being homozygous for a certain locus
by receiving both alleles of this locus
from ancestral source.
• Offspring of first-cousin marriage is
homozygous at 1/16 of his loci.
Factors Affecting Gene Frequency
in a Population:
1.
2.
3.
4.
5.
Non-random mating.
Altered mutation rate.
Selection.
Small populations.
Migration.
1. Non-Random Mating:
• The offspring of these mating are at
an increased risk of homozygosity for
any recessive alleles carried by the
common ancestor(s).
2.
Altered Mutation Rate:
• New hereditary variations arise by mutation, and the
new gene is called a mutant.
• The spontaneous mutation rate (u) varies for
different loci:
(u = n/2 N)
(n = no. of cases with mutent gene / N =
Total No. of births) Who have normal
parents
• The rate is easier to measure in dominant
genes. Dominant traits require a mutation
rate in only one of the two gametes concerned.
3. Selection:
• Genetic selection acts on the individual
phenotypes and either favours or hinders
reproduction and thus the propagation of that
individual’s genotype.
• Acts by modifying an individual’s biological
fitness (F).
• For an autosomal dominant trait, any
increase in (F), will rapidly alter the gene
frequency over the next few generations to a
new equilibrium.
Selection: (Cont’d)
• Selection against a recessive genotype is less
effective and result in a slow change in gene
frequencies.
• For X-Linked recessive trait, the situation
is intermediate between autosomal dominant
and recessive.
4.
Small Populations:
• For religious, geographical, tribal or other
reasons a small group of individuals may
become genetically isolated from the rest of
the population (genetic isolates).
• By chance one allele may fail to be passed on
to the next generation and so disappear
(extinction) leaving only the alternative
allele at that locus (fixation).
5.
Migration:
• Migrant individuals will modify the gene
pool of their descendents.
• ABO blood group system – B allele.
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