Population Genetics

Chanin Limwongse, MD
Chintana Sirinavin, MRCP
 Population Genetics

 The study of gene distribution in population

 How gene frequencies or genotypes are
maintained or changed
 Concerns both genetic factors (mutation
and mating) and environmental factor
(selection and migration)
What happens with a mutant gene ?

 Existing in decreased number until

disappearance
 Existing in increased number

 Existing in stable number

Gene frequency

 Balance between new mutation rate,

fitness, selection and other factors

 New mutation rate = rate of allele loss

 Gene frequencies vary among
different ethnic groups
 Europian / US Caucasian: cystic fibrosis,
hemochromatosis
 French Canadian: PKU, OPMD, familial
hypercholesterolemia
 Ashkenazi Jews: Tay-Sachs, dysautonomia

 African: sickle cell anemia

 Asian: α and β thalassemia

 Hardy-Weinberg Law

 Use in calculating genotype frequency from

phenotype data

 p = frequency of allele A
 q = frequency of allele a

 p+q = 1
 Hardy-Weinberg Law

 Frequency of genotype AA = p2
 Frequency of genotype aa = q2

 Frequency of genotype Aa = 2pq

 Sum of all genotype = p2 + 2pq + q2

= (p+q)2
=1
 Hardy-Weinberg Law

 Proportion of each genotype (AA:Aa:aa)

will remain constant at equilibrium if allele
frequencies remain constant
 Hardy-Weinberg Law

 For an autosomal recessive disease,

disease phenotype is found in population
at a frequency of 1/3600

 Then carrier frequency = 2x 1/√3600

= 1/30
o Gene frequency = q = 1/60
 Hardy-Weinberg Law

 For an autosomal dominant disease,

allele frequency = ½ x population
frequency of disease

 For X-linked recessive disease, allele

frequency = disease frequency in male
 Factors that disturb Hardy-
Weinberg equilibrium (1)
 Non-random mating
stratification (ethnic subgroup)
assortive mating
consanguinity
 All of the above will tend to increase
homozygote frequency and decrease
heterozygote frequency for AR disorder
 Factors that disturb Hardy-
Weinberg equilibrium (2)

 Non-constant allele frequency

reduced fitness (<1) or no fitness (= 0)
selection against disease allele esp.
for AD disorder
genetic drift
gene flow
 Selection against dominant allele

 Lethal dominant disease or disease with near

zero fitness
 Results in no transmission of disease through
parents
 Most cases are from new mutation
 Disease frequency remain constant if new
mutation rate is high enough
 Population frequency will not comply with
Hardy-Weinberg equilibrium
 Example of disease with
zero fitness
 Apert syndrome
 Thanatophoric dysplasia

 Cornelia de Lange syndrome

 Atelosteogenesis

 Acrodysostosis

 Osteogenesis imperfecta type 2

 Selection and mode of
inheritance
 AD – significant due to expose of phenotype in
heterozygote
 AR – negative selection has minimal effect due to
most are carrier without phenotype thus
no selection against
- positive selection in carrier may maintain high
gene frequency in population
 XR – selection operates in hemizygous male only
therefore about 1/3 of alleles are lost in
a generation if fitness = 0
 Genetic drift vs, Gene flow

 Drift: Fluctuation in gene frequency due

to chance
 Flow: Slow diffusion of genes due to
population admixture
 Example : drift: breaking off of a
subpopulation from a larger population
flow: migration of population
and merge with larger one