Phenotypes, genotypesPhenotypes, genotypes

Populations geneticsPopulations genetics

RNDr Z.PolívkováRNDr Z.Polívková

Lecture No 428 - Lecture No 428 - course: Heredity

Population genetics distribution of genes in populations

No of individuals with traitFrequency 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

GenotypesAA p2 Aa 2pq aa q2

AA p2 p4 2p3q p2q2

Aa 2pq 2p3q 4 p2q2 2pq3

aa q2 p2q2 2pq3 q4

Each of three paternal genotypes may mate with each of three maternal genotypes

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

genotypes of offspring

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 = 1Ex.:Frequency of alleles A,B,0 in AB0 blood groups: p,q,rFrequency 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 malesFrequency 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 – sExample: 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 mutationsExample: 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 advantageExample: 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

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