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
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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
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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
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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
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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
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6
Q

What factors determine persistence of new mutations?

A
  • Type of mutation ( dominant, recessive, X-linked)
  • Selection (positive, neutral, negative)
  • Population effect
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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
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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
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9
Q

+ Heterozygote advantage example in wild horse populations:

A
  • TRPM1 gene
  • Heterozygote: Leopard complex spotting
  • Homozygote: Congenital night blindness
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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
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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)
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12
Q

How is heritability traditionally estimated?

A
  • Plotting trait in offspring against parents (e.g. height), extrapolating slope gradient -> % heritability
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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)
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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
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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
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