Population Genetics

Question 1

Polymorphisms

Answer 1

Allelic variants that are present in more than 1% of the population; highly polymorphic genes determine individual characteristics (ex. HLA haplotypes and p450), while nonpolymorphic genes cannot be mutated without causing serious problems (ex. histones)

Question 2

Genetic polymorphisms in human populations

Answer 2

Approximately 6 million single nucleotide polymorphisms (SNPs) between unrelated humans, variation in copy numbers between individuals due to presence of insertions and deletions (0.4% of genome)

Question 3

Genetic variation between different ethnic groups

Answer 3

90% of world’s polymorphisms are found in any given population, so only 10% polymorphic difference between races

Question 4

4 assumptions of Hardy-Weinberg principles

Answer 4

1. Large population
2. Genotypes all have same fitness
3. Mating is random
4. No influx or efflux of alleles

Question 5

What 4 influences are there on Hardy-Weinberg principles?

Answer 5

1. Genetic drift (population is small)
2. Selection (fitness of offspring is unequal)
3. Assortative mating (mating is nonrandom)
4. Population bottlenecks and founder effect

Question 6

Calculate allele and heterozygote frequencies using the Hardy Weinberg equations

Answer 6

4 possible genotypes are aa, Aa, aA, and AA, so probabilities are f(a)^2 for aa, f(A)^2 for AA, and 2f(a)f(A) for heterozygotes – PRACTICE THIS WITH QUESTIONS

Question 7

Genetic drift

Answer 7

Effect of statistical variation from small populations that leads to disappearance or multiplication of rare alleles

Question 8

How does genetic drift affect the gene pool of a population?

Answer 8

Leads to loss of more alleles due to disappearance in small population (typically, but can be GAIN of alleles); recessive alleles disappear more slowly than dominant

Question 9

How does selection affect the gene pool of a population?

Answer 9

Eliminates detrimental alleles (negative selection); but positive selection of heterozygotes can occur due to reduced incidence of certain disorders (ex. sickle cell and thalassemia against malaria, CFTR against typhoid, and hemochromatosis against plague)

Question 10

How does assortive mating affect the gene pool of a population?

Answer 10

Selection of partners due to specific genetic trait that disturbs distribution of alleles and leads to a loss of heterozygosity – DOES NOT AFFECT ALLELE FREQUENCY OVER TIME (ex. consanguineous matings)

Question 11

How does founder effect affect the gene pool of a population?

Answer 11

Can lead to amplification of rare alleles so that the genotype is amplified

Question 12

Population bottlenecks

Answer 12

Selection for homozygotes due to bottleneck recovery (amplification of rare alleles)

Question 13

Heterozygote advantage in respect to mutations affecting CFTR

Answer 13

Preventative against typhoid fever due to resistance to S. typhimurium bacterium that makes it difficult for it to enter bloodstream well

Question 14

Heterozygote advantage in respect to mutations affecting β-globin

Answer 14

Both sickle cell and thalassemia protect against malaria due to mutation in hemoglobin

Question 15

Heterozygote advantage in respect to mutations affecting HFE

Answer 15

Protection against the plague

Question 16

Ellis van Creveld syndrome

Answer 16

Rare autosomal recessive disease caused by mutations in EVC genes that is common in Old Order Amish of Lancaster County (carrier frequency is 12.3% compared to normal 0.8% in rest of population)

Question 17

Tay-Sachs disease

Answer 17

Ganglioside storage disease prevalent in Ashkenazi Jews

Question 18

Tyrosinemia

Answer 18

Disorder common in French Canadians in Quebec

Question 19

Ancestry

Answer 19

Genetic ancestry is calculated best by looking at all 5 million SNPs of a genome

Question 20

Genome-wide association studies (GWAs)

Answer 20

Millions of SNPs analyzed to compare prevalence of certain SNPs in patients to prevalence in control cases

Question 21

Epidemiological studies

Answer 21

A way of measuring contribution of polymorphisms to disease

Question 22

Linkage equilibrium

Answer 22

Two close markers in a population are associated half the time

Question 23

Linkage disequilibrium

Answer 23

Two close markers are associated more frequently than expected by chance; an important way of characterizing genetic history of a population using young, genetically isolated (aka small) populations (high degree of disequilibrium); establishes which recombinations are more prevalent before the population reaches an equilibrium – only observed when disease-causing mutation is introduced recently

Question 24

Type I diabetes in Dutch village

Answer 24

Found mutations increasing the risk through founder effect and linkage disequilibrium