Exam 5: Population Genetics Flashcards
ancestry
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
epidemiological studies
measure contributions of certain genetic polymorphisms (which underlie susceptibility) to disease
uses genome-wide association studies (GWAS) to compare prevalence of certain SNPs
SNPs & diseases
SNPs not necessarily disease-causing mutations
often lie outside coding regions - show strong linkage with mutations contributing to disease
founder effect
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
genetic drift
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
genome-wide association studies (GWAS)
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
polymorphic allele
allelic variants, present in more than 1% of population
highly polymorphic genes
determine individual characteristics
Nonpolymorphic genes
code for proteins with essential cellular functions, mutations in these are incompatible with life
population bottleneck
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
Ever human can be expected to carry
3 deleterious recessive mutations
How many SNPs are there between unrelated humans?
6 million (about 0.1% of genome)
How much of world’s polymorphisms can be found within any given population?
90%
How any polymorphisms set apart races?
10%
Hardy-Weinberg equations
calculate allele frequencies in gene pools and genotype frequencies in ideal populations - allele frequencies do not change over time in ideal populations
Ideal populations have following characteristics:
large population size, equal fitness of offspring, random mating, no influx of new alleles by migration or mutations
Probability of being heterozygous (Aa) using Hardy-Weinberg equation (carrier frequency)
2f(a)f(A)
or 2*sq.root of prevalence
Probability for being homozygous for an allele using Hardy-Weinber equation
f(a)^2 or f(A)^2
allele frequency of a gene pool
f(A) = 1-f(a)
if recessive disease is 1/10,000, f(a)=1/100
f(A) = 0.99
X-linked recessive allele frequency
fraction of males who are affected
selection
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)
positive selection of heterozygotes (heterozygote advantage)
responsible for high mutant allele frequencies
Some heterozygote alleles are favored - disease preventing
heterozygote advantage in CFTR
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
heterozygote advantage in Hemoglobin B
homozygous state = sickle cell anemia or B-thalassemia
heterozygous = protects against malaria
heterozygote advantage in HFE
homozygous state = Hemochromatosis
heterozygous protects against plague
Assortative mating
selection of partners based on specific genetic trait
disturbs equilibrium of alleles
consanguineous matings
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
Ellis van Creveld syndrome
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
Diseases affecting genetically isolated populations
Ellis van Creveld Syndrome - Old Order Amish of Lancaster County
Tay-Sachs Disease - Ashkenazi Jews
Tyrosinemia - French Canadians (Quebec)
linkage disequilibrium
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