Population Genetics

Natural selection, mutation, random genetic drift, migration

(4) Types of Population Genetics

p^2 + 2pq + q^2 = 1

Hardy Weinberg Equation (formula)

p^2

Frequency of homozygous allele A (dominant)

q^2

Frequency of homozygous allele a (recessive)

2pq

Frequency of heterozygous alleles

Mutation, natural selection, random, migration, drift, large

Hardy Weinberg Law Assumptions

• No __ occurring at the locus

• __ __ is not occurring

• Completely __ mating

• No net __ and no random genetic __

• __ population

Hardy Weinberg Equation

Formula allows prediction of genotypic frequency of next generation

1 = p^2 + 2pq + q^2 = (p x q)^2

Distribution of genotypes in next generation (equation)

Bottleneck Effect

Drastic reduction in population size, species have reduction in gene pool

Founder Effect

Subpopulation breaks off from larger population, species have reduction in gene pool

Metabolism, metabolite, pharmaco

Drug Metabolism

Genetic variants with decreased drug __ means low __ activity, and increased __logical effect

Poor metabolizer

Much less of this drug type is converted to active form

low, Warfarin, high

Warfarin

• For a decreased metabolizer drug, a __ (low/high) dose of __ is needed

• For a high metabolizer drug, a __ (low/high) dose of Warfarin is needed

Ultra-rapid metabolizer, poor metabolizer

CYP2D6 Phenotypes

• Activity score more than 2 = ___ __, give high dose of drug

• Activity score of 0 = __ __; give low dose of drug

Codeine, metabolite, morphine, adverse

CYP2D6 ultra-rapid metabolizers should NOT receive __ as it is converted to active __, aka __

• There is an increased risk of __ side effect, avoid drug altogether

C

Patient is experiencing pain following a surgical procedure and a clinician wants to prescribe codeine to treat the pain. The patient has a pharmacogenetic activity score of greater than 2. Based on the pharmacogenetic test result, what recommendation would you do?

a) Use label recommended dosing
b) Reduce the initial starting codeine dose by 50%
c) Avoid codeine due an increased risk of severe side effects
d) Avoid codeine due to a lack of analgesic effects

Assortative mating

A male with a loss-of-function mutation in the GJB2gene mates with a female with a mutation in the same gene. What best describes this exception to the Hardy-Weinberg assumptions?

Heterozygous advantage

The decrease in malaria cases in individuals that are carriers for mutations in the beta-globin gene is an example of which principle?

Founder effect

French-Canadians have 22 unique mutant alleles that are not shared in the same frequency in the French population. What best describes the difference in the two populations?

Diplotype

Henderson has deoxycytidine at positon 6,889,648 on the OR6A2gene and hates cilantro.  Dr. Brooks has deoxyadenosine at position 6,889,648 and likes cilantro.

What best describes this common genetic variation?

Increase dose

Your patient’s pharmacogenetics lab results indicate that they have one loss-of-function allele for CYP2D6 and one normal allele.  You want to prescribe a drug that is transformed into its active form by CYP2D6.  What adjustments do you need to make to the dose for this patient?

A. Increase dose

B. Decrease dose

C. No change, standard dose

Increase dose

A patient that is an ultrafast metabolizer for CYP2C19, the cytochrome P450 protein responsible for the breakdown of the active form of a new drug.  What adjustments do you need to make to the dose for this patient?

A. Increase dose

B. Decrease dose

C. Avoid drug