L3, Genetic variation in populations Flashcards
1
Q
Hardy Weinberg: - use, assumptions
A
- See FCs
- Applies only if mating is random and population is stable
- Able to use to predict genotype frequency based on known allele frequency in a population
2
Q
Assumptions of Hardy-Weingberg rule:
A
- Mating is random -> humans actually mate assortatively e.g. religion
- -> Likely not a major interference with H-W overall due to scale of populations
- No inbreeding (critical!)
- Allele frequencies remain constant across generations
3
Q
Why may allele frequencies vary across generations?
A
- Mutation -> take a long time to reach appreciable frequencies in populations
- Selection (e.g. heterozygote advantage)
- Genetic drift (particularly in small populations) -> random changes in population
4
Q
How is inbreeding quantified?
A
- Coefficient of relationship (R) = proportion of alleles shared by two people having common ancestors -> Sum of (1/2)^n where n = number of links through a common ancestor
- Coefficient of inbreeding (F) = proportion of loci at which individual is expected to be homozygous -> 1/2R of parents
5
Q
ROH:
A
- Runs of homozygosity
- Important when considering and fitness
- -> Researchers have calculated that first cousins are 55% less likely to have children; associated with ROH and not common variant homozygosity
6
Q
What factors determine persistence of new mutations?
A
- Type of mutation ( dominant, recessive, X-linked)
- Selection (positive, neutral, negative)
- Population effect
7
Q
Frequency of mutations in generation -> affected protein-coding genes?
A
- 1 per 30 million bps per generation
- Average of 1 protein-coding gene per generation
8
Q
What is heterozygote advantage?
A
- The case in which the heterozygous genotype has a higher relative fitness than either AA or aa
- e.g. Sickle cell trait protects against malaria in
9
Q
+ Heterozygote advantage example in wild horse populations:
A
- TRPM1 gene
- Heterozygote: Leopard complex spotting
- Homozygote: Congenital night blindness
10
Q
Describe the founder effect:
A
- Loss of genetic variation that occurs when a new population is established by a very small number of individuals from a larger one
- Also increases frequency of previously rare alleles e.g. Ashkenazi Jews with a high prevalence of particular rare diseases
11
Q
Heritability:
A
- How much of the observed variation in a trait is caused by genetics
- Highly penetrant, single gene disorders should have a heritability of 0 (no variation)
12
Q
How is heritability traditionally estimated?
A
- Plotting trait in offspring against parents (e.g. height), extrapolating slope gradient -> % heritability
13
Q
Current methods for estimating heritability:
A
- Calculating lambda values: risk to sibling / population risk
- Risk to sibling is calculated using proportion of affected probands in a study who have an affected sibling
- Twin concordance studies (monozygous vs dizygous)
- Adoption at birth (many complications; need a large number for estimating heritability)
14
Q
Pharmacogenetics:
A
- Side effects conferred by genetic factors
- Also includes sensitivity to particular drugs (e.g. warfarin - 20% variation in safe, effective dose)
- Pharmacodynamics
- Pharmacokinetics
15
Q
Examples of drugs with serious side effects conferred by genetics:
A
- Azathioprine -> immunosupressant that produces neutropenia in those with low TPMT activity
- Fluorouracil -> cancer drug which is toxic to nervous system in some individuals
- Succinylchloride -> muscle relaxant which produces prolonged apnea in those with low butyrylcholinesterase activity
- Warfarin -> anticoagulant that produces excessive bleeding in those with low CYP2C9 activity