Lecture 3: Genetic Variation in Populations Flashcards
What is p and how is is calculated?
frequency of normal allele in a population
p = number of normal alleles/total number of alleles
What is q and how is it calculated?
frequency of disease allele in a population
q = number of disease alleles/total number of alleles
What is the Hardy-Weinberg equation?
p^2 + 2pq + q^2 = 1
where p^2 = AA
2pq = Aa
q^2 = aa
What are the assumptions made when using the Hardy-Weinberg equation?
- mating is random
- population is stable (allele frequencies remain constant across generations)
- no inbreeding
What is the carrier frequency of an autosomal recessive disease?
2pq (frequency Aa heterozygote)
How would you calculate the probability of you having a child with autosomal recessive disease when both you and unrelated partner have no history of the disease?
(2pq)^2 x 0.25
0.25 = the probability of two carriers (Aa) having an affected child (aa)
How would you calculate the probability of you having a child with autosomal recessive disease when both you have a sibling with the disease but you are unaffected and your partner has no history of the disease?
Sibling with the disease = both parents must be carriers
but since you are unaffected (not aa) so your chance of being a carrier (Aa) is 2/3 and chance of not being carrier (AA) is 1/3.
Therefore
2pq (carrier frequency for partner) x 2/3 (carrier frequency for you) x 0.25 (for chance of having affected child)
2pq x 2/3 x 0.25
What is the coefficient of relationship (R) and how is it calculated?
The proportion of alleles shared by two people by having common ancestors (identity by descent - identical at same locus by inheriting same allele from ancestor)
Calculated by: (1/2)^n
1/2 = chance of inheriting an allele from a parent
n = number of links through common ancestor between two individualsW
What is the coefficient of inbreeding (F) and how is it calculated?
The proportion of loci at which an individual is expected to be homozygous due to inbreeding
calculated by: 1/2R (1/2 coefficient of relationship)
If the chance of one person being a carrier is 2pq, what is the chance that their first cousin is also a carrier at that locus?
1/8 (the coefficient of relationship, R, for cousins)
cousin - parent - grandparent - parent - cousin = 4 paths = 1/2^4 = 1/8
What is relative risk and how is it calculated?
Relative risk is the risk of having an affected child for a particular couple (E.g. first cousin marriage) compared to the risk of having an affected child for unrelated parents in general population.
Calculated by:
risk of particular couple having affected child/risk of general population having an affected child
E.g. is risk of affected child for first cousin marriage is 1 in 744 and the risk of affected child in general population is 1 in 2160, then 2160/744 = RR ~ 3
True or false: relative risk of having an affected individual is lower for inbreeding couples?
False: RR is higher (although the actual risk may still be quite low, it is just much higher compared to general population)
What does the persistence of a mutation within a population depend on?
- type of mutation (dominant, recessive, X-linked)
- selection (positive, neutral, negative effect of mutation)
How does persistence of deleterious/harmful mutations in a population vary for:
1. Dominant lethal
2. Dominant affecting fertility
3. Late onset dominant
4. X-linked lethal
5. Autosomal recessive
- Dominant lethal: persist for single generation
- Dominant affecting fertility: persist for one to a few generations
- Late onset dominant: persist for many generations
- X-linked recessive: 1/3 lost per generation
- Autosomal recessive: persists for many generations but mostly eventually lost
What balances the persistence of deleterious mutations?
de novo mutations ??????????????????????????????????
How does heterozygote advantage allow persistence of mutant allele in a population?
give an example
Heterozygote may confer a selective advantage that increases survival in those individuals
E.g. for Sickle cell anaemia autosomal recessive disorder, aa = SCA, AA = susceptible to malaria, but Aa heterozygotes do not have SCA and are resistant to malaria so increased survival of heterozygotes that pass on the mutant allele.
What is the founder effect?
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What is heritability?
how much of the observed variation in a trait is caused by genetics
What is the theoretical heritability of highly penetrant single gene disorders?
should have a heritability of 0 (i.e. no variation) - but some variability comes from modifier genes and environmental influences
Multifactorial traits?
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True or false: complex genetic diseases are inherited in a mendelian fashion?
False, not single gene
but they do tend to run in families
How is heritability estimated traditionally?
plot trait for offsprings and parents and determine the slope of the line to see correlation.
Slope of 1 = 100% of variation due to genetic
What does a slope of 0.84 mean in terms of heritability?
84% of variation in the trait can be accounted for by genetic variation (84% heritability)
What does an odds ratio of 1 mean?
there is no effect of a given factor on the development of a disease
Other than slope of line, how else can heritability be estimated (more commonly)?
Heritability is commonly estimated using risk to 1st degree relative of an affected individual compared to the rest of the population (λs) - relative risk
What is λs?
the fold greater chance of having a disease if sibling is affected (Relative risk)
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