Exam 5: Population Genetics

Question 1

ancestry

Answer 1

genome-wide SNP analysis can be used to calculate accurate parameters of genetic ancestry (membership to certain population)
data reflects human migration and admixture - more accurate than physical appearance & race

Question 2

epidemiological studies

Answer 2

measure contributions of certain genetic polymorphisms (which underlie susceptibility) to disease
uses genome-wide association studies (GWAS) to compare prevalence of certain SNPs

Question 3

SNPs & diseases

Answer 3

SNPs not necessarily disease-causing mutations

often lie outside coding regions - show strong linkage with mutations contributing to disease

Question 4

founder effect

Answer 4

new territory populated by small founder population
eventually everyone is related (inbreeding inevitable) and homozygosity increases
Lead to amplification of rare alleles - genotype of founder population amplified proportionally as population grows

Question 5

genetic drift

Answer 5

effect of statistical variation (in small populations, normal statistical variation can have large impact)
can lead to disappearance or multiplication of rare alleles, without selection for or against it - chance

Question 6

genome-wide association studies (GWAS)

Answer 6

millions of SNPs analyzed to compare prevalence of certain SNPs in patients to their prevalence in control cases
Odds ratio calculated for each SNP that describes strength of association of SNP with disease

Question 7

polymorphic allele

Answer 7

allelic variants, present in more than 1% of population

Question 8

highly polymorphic genes

Answer 8

determine individual characteristics

Question 9

Nonpolymorphic genes

Answer 9

code for proteins with essential cellular functions, mutations in these are incompatible with life

Question 10

population bottleneck

Answer 10

large part of population wiped out by catastrophic event & has to recover from small founder population of survivors
population bottleneck leads to amplification of rare alleles in founder’s genotype that provide a selective advantage

Question 11

Ever human can be expected to carry

Answer 11

3 deleterious recessive mutations

Question 12

How many SNPs are there between unrelated humans?

Answer 12

6 million (about 0.1% of genome)

Question 13

How much of world’s polymorphisms can be found within any given population?

Answer 13

90%

Question 14

How any polymorphisms set apart races?

Answer 14

10%

Question 15

Hardy-Weinberg equations

Answer 15

calculate allele frequencies in gene pools and genotype frequencies in ideal populations - allele frequencies do not change over time in ideal populations

Question 16

Ideal populations have following characteristics:

Answer 16

large population size, equal fitness of offspring, random mating, no influx of new alleles by migration or mutations

Question 17

Probability of being heterozygous (Aa) using Hardy-Weinberg equation (carrier frequency)

Answer 17

2f(a)f(A)

or 2*sq.root of prevalence

Question 18

Probability for being homozygous for an allele using Hardy-Weinber equation

Answer 18

f(a)^2 or f(A)^2

Question 19

allele frequency of a gene pool

Answer 19

f(A) = 1-f(a)
if recessive disease is 1/10,000, f(a)=1/100
f(A) = 0.99

Question 20

X-linked recessive allele frequency

Answer 20

fraction of males who are affected

Question 21

selection

Answer 21

will reduce number of detrimental mutant alleles in population (as selection favors against mutant allele)
frequency of mutant alleles will stabilize at low level (negative selection equals occurrence of new mutations)

Question 22

positive selection of heterozygotes (heterozygote advantage)

Answer 22

responsible for high mutant allele frequencies

Some heterozygote alleles are favored - disease preventing

Question 23

heterozygote advantage in CFTR

Answer 23

In homozygous state causes Cystic fibrosis
Heterozygote protects against Typhoid fever
have higher resistance to S. typhimurium bacterium which binds to nonmutated CFTR protein to enter human - can not enter bloodstream as well
people heterozygote for CFTR lived during Typhoid epidemics and passed on the mutant allele
Populations with repeated typhoid exposure have high CFTR mutant allele frequencies and a high incidence of cystic fibrosis

Question 24

heterozygote advantage in Hemoglobin B

Answer 24

homozygous state = sickle cell anemia or B-thalassemia

heterozygous = protects against malaria

Question 25

heterozygote advantage in HFE

Answer 25

homozygous state = Hemochromatosis

heterozygous protects against plague

Question 26

Assortative mating

Answer 26

selection of partners based on specific genetic trait

disturbs equilibrium of alleles

Question 27

consanguineous matings

Answer 27

mating of genetically similar individuals increases degree of homozygosity in population
does not change allele frequencies in gene pool - only change is an increase in homozygote frequency above expected level = increase in recessive diseases

Question 28

Ellis van Creveld syndrome

Answer 28

EVC gene recessive mutation
affects genetically isolated populations - propagation of rare allele in Old Order Amish of Lancaster County (carrier frequency 12.3% vs. general population 0.8%)
skeletal dysplasia, shortening of forearms and lower legs, postaxial polydactyly and heard defects

Question 29

Diseases affecting genetically isolated populations

Answer 29

Ellis van Creveld Syndrome - Old Order Amish of Lancaster County
Tay-Sachs Disease - Ashkenazi Jews
Tyrosinemia - French Canadians (Quebec)

Question 30

linkage disequilibrium

Answer 30

original combination of alleles is found more frequently than predicted
find alleles that contribute to certain disease - find markers that are more often associated with disease trait than predicted by allele frequency alone
Genetically young populations (LD observed when disease introduced to population recently) & small populations (only few genes with little heterogeneity contributing to disease) most useful in these studies