Phenotypes, genotypes
Populations genetics
RNDr Z.Polívková
Lecture No 428 - course: Heredity
Population genetics
distribution of genes in populations
No of individuals with trait
Frequency of trait =
(allele, genotype)
No of all individuals in population
frequency
1/2500, 1 : 2500, 0.004
Human population – 3 races – Caucasians, Blacks, Asians
genetically different (in allele frequencies)
also ethnic groups are genetically different
The basis of genetic differences: mutations
selection, degree of reproductive isolation
Examples of differences
albinism in some Indians
sickle cell anemia in Blacks in Africa
β-thalasemia – regions around Mediterranean sea
cystic fibrosis in Caucasians – high frequency
low in Finland, in Asian and African population
Finland : XR choroideremia - rare X-linked eye disease
only 400 cases in the world – 1/3 in Finland
high frequency of 20 disorders – rare elsewhere in the world
low frequency of CF (cystic fibrosis) and PKU (phenylketonuria)
South Africa – high frequency of Huntington disease,
porphyria variegata (AD defect of hemoglobin)
in white population of South Africa
Thompson & Thompson: Genetics in medicine, 7th ed., 2007
Passarge: Color Atlas of Genetics, 1995
Calculations of alleles and genotypes frequencies from
frequency of disorder:
The Hardy – Weinberg low
f(A) = p, f(a) = q - 1 locus with 2 alleles
p + q = 1 - alleles frequencies
gametes
A
p
a
q
A
p
AA
p2
Aa
pq
a
q
Aa
pq
aa
q2
p2 + 2pq + q2 = 1 – genotypes frequencies
(p + q)2 = 1
Each of three paternal genotypes may mate with each of three maternal genotypes
Genotypes
AA p2
AA
p4
p2
Aa
2pq aa q2
2p3q
p 2q 2
Aa
2pq 2p3q
4 p 2q 2
2pq3
aa
q2
2pq3
q4
p 2q 2
genotypes of offspring
mating types
Frequency of matings
AA
Aa
aa
1.AA x AA
p4
p4
-
-
2.AA x Aa
4p3q
2p3q
2p3q
-
3.AA x aa
2p2q2
-
2p2q2
-
4.Aa x Aa
4p2q2
p2q2
2p2q2
p2q2
5.Aa x aa
4pq3
-
2pq3
2pq3
6.aa x aa
q4
-
-
q4
Offspring:
AA : p4 + 2p3q + p2q2 = p2 (p2 + 2pq + q2) = p2
Aa: 2p3 q + 2p2q2 + 2 p2q2 + 2pq 3 = 2pq(p2 + 2pq + q2) = 2pq
aa : p2q2 + 2pq3 + q4 = q2 (p2 + 2pq + q2) = q2
p2 + 2pq + q2 = 1
Genotypes are distributed in proportions to
the frequencies of individual alleles in a
population and these proportions remain
constant from generation to generation
Frequency of autosomal recessive disorder = q2
Frequency of autosomal dominant disorder = p2 + 2pq
3 alleles – frequencies - p, q, r
p+q +r=1
(p + q + r )2 = 1
Ex.:Frequency of alleles A,B,0 in AB0 blood groups: p,q,r
Frequency of genotypes: AA + A0 = p2 + 2pr
BB + B0= q2 + 2qr
AB = 2pq
0 = r2
X-linked genes
♂
p+q=1
♀
p2 + 2pq + q2 = 1
Frequency of mutant allele = frequency of affected males
Frequency of normal allele = frequency of normal males
Condition of HW equilibrium:
• random mating
• balance between mutation and selection
• no migration
• large population
Disturbance of gene frequencies in population:
1. Non random mating
- stratification – population subgroups
mating in restricted
- assortative mating – choise of a mate
- consanquinity – risk of AR diseases
→ increase in proportion of homozygotes,
decrease in proportion of heterozygotes
2. Mutation and selection
lethal mutation = is not transmitted to the next generation
= Selection against AD mutations
- against homozygotes and heterozygotes
- effective in a single generation
Deleterious mutation, but not lethal
Coefficient of selection s
Fitness (ability to reproduce)
f=1–s
Example: achondroplasia (dwarfism)
f = 0.2 (only 20% of affected people have children)
s = 0.8 = 80% are new mutations
= constant frequency of disease
Selection against AR mutations
- less effective – mutation are maintained in heterozygotes
Selection against XR mutations
Example: DMD (Duchenne muscular dystrophy)
1/3 of alleles lost in each generation
1/3 of cases = new mutation
Selection against heterozygotes
in Rh maternal – fetal incompatibility
= haemolytic disease in Rh+ newborns (Rh- mother)
Heterozygote advantage
Example: sickle cell anemia (AR)
- highest frequency in West Africa in regions with endemic malaria
- lower frequency in Blacks in U.S.
Heterozygotes – resistence to malarian parasite
low fitness: homozygotes AA – suffer from malaria
homozygotes aa – suffer from sickle cell anemia
Passarge: Color Atlas of Genetics, 1995
3. Small populations – genetic drift = change in gene
frequency
Founder effect = one of the original founders of a new
population carries a rare allele
allele may become fixed in a new population or can
disappear from population
it depends on a chance
in case of fixation of allele = relatively high frequency in small
breeding population in relatively short time
Example: The Afrikaners (South Africa)
in 1652 settlers from Holland
1 was carrier of Huntington disease (AD)
1 was carrier of variagate porphyria (AD)
All current carriers are direct descendents of this original carriers
High frequency of these diseases in this country (rare elsewhere)
Each population is characterised by its own
molecular mutations
4. Migration - gene flow = slow diffusion of genes across
barriers (geografical, racial…)
gradual changes in large populations
Mechanism = migration
Example: B allele (AB blood groups)
declines from Asia (f = 0.3) to Europe ( f = 0.06)
Spreading of mutation in agreement with migration of some
populations
Example: Celtic mutation in cystic fibrosis, phenyketonuria
5. Eugenics
Positive - selective breeding (plants, animals)
Negative – elimination of some genotypes (genetic counselling,
prenatal diagnosis)
Medical treatment – reduces selection, maintains mutant alleles
in population, enables transfer of mutant alleles to the next
generation
Genetic counselling prenatal diagnosis – reduction of incidency
of some disorders, but it retains healthy heterozygotes
Thompson &Thompson: Genetics in medicine,7th ed.
Chapter 9: Genetic variation in individuals and population: Mutation
and polymorphism (from page 192)
+ informations
from presentation
http://dl1.cuni.cz/course/view.php?id=324