Genetic Variation in Populations Flashcards
Allele and genotype frequencies
Frequency of A in population (p) - Number of A alleles/total number of alleles
Frequency of a in population (q) - Number of a alleles/ Total number of alleles
Think of p and q as GAMETE genotype frequencies across a population
p+q=1
Genotype frequencies:
AA - p2
aa - q2
Aa = 2pq
p2 + q2 +2pq = 1
When to use hardy weinberg
Mating random
Population stable
Using hardy-Weinberg to calculate cystic fibrosis carrier frequency
Carrier frequency = 2pq
Incidence of CF affected individials - q2- 1/2000 = 0.0005
q = Square root of 0.0005 = 0.022
p+q = 1 therefore p=1-0.022 = 0.978
2pq = 2 x 0.978 x 0.022 = 0.043 or 1 in 23
Calculating probability of having child with CF
- Unrelated partner - no CF history
0.043 squared (probability of both being carriers) x 0.25 (Probability of two carriers of having an affected child) = 4.6x10^-4 = approx 1 in 2160 - Sibling with CF
0.043 x 2/3 (parents carriers, individual unaffected) x 0.25 = 0.072 = approx 1 in 140
- consider testing of partner
Assumptions of hardy weinberg rule
- Mating random
- No inbreeding
- Allele frequencies remain constant across generations - Mutation, selection e.g. heterozygote advantages, genetic drift (random changes in population)
Measures of inbreeding
- Coefficient of relationship (R) - Proportion of alleles shared by two people by having common ancestors (identity by descent)
sum of (½)n where n = number of links through a common ancestor between two individuals
for full siblings: (½)2 + (½)2 = ½
Coefficient of inbreeding (F): proportion of loci at which individual is expected to be homozygous
½R of parents
if parents are cousins F = ½(½4 + ½4) = 1/16 = 0.0625
Inbreeding and risk of recessive disease
For first cousins (Janet and John) and CF:
chance of John being carrier for cystic fibrosis = 0.043 (q = 0.022)
chance of Janet being carrier if John is a carrier = 1/8 (R for cousins)
chance of both being carriers and having an affected child = 0.043 x 0.125 x 0.25 = 0.0013 or 1 in 744 (compared to 1 in 2160 if they were unrelated)
Inbreeding and fitness - general
5 categories:
reproductive success, risky behaviours, cognitive ability,
body size,
health
Especially males
Mutations
- 1 per 30 million base pairs per generation (100 per genome)
Average of one protein-coding gene per generation
Persistence depends on:
- Type of mutation (dominant, recessive, X-linked)
- Selection (positive, neutral, negative)
Persistence of deleterious mutations
- Dominant lethal - single generation
- Dominant conditions affecting reproductive success: one t0 a few generations
- Late onset dominant (e.g. Huntington’s): many generations
- X-linked lethal: 1/3 lost per generation
- Autosomal recessive: several-many generations but mostly eventually lost, depending on pop size, selective disadvantage
Balanced by de novo mutations
Random drift: Founder effect
Source population - Contains mutant alleles
->
Founder of new populations
->
New population - Reduced variability and increases frequency of previously rare alleles
Multifactorial traits
e.g. height, skin colour, susceptibility to disease, response to drugs
Number of genes:
Single gene -> Polygenic
Vp = Vg + Ve -> Heritability -> h2 = Vg/Vp
Heritability
How much of the observed variation in a trait is caused by genetics
Highly penetrant, single gene disorders should have heritability of 0 (no variation)
In reality – nearly always some variability (effects of modifier genes + environment)
Complex genetic diseases
- Unlike Mendelian disorders, there is no clear pattern of inheritance
But tend to “run” in families
Few large pedigrees of multiply affected individuals
Most people have no known family history
