population genetics is?
the application of genetic principles to entire populations or organisms
population = group of organisms of same species living in same geographical area
may be within a population
allele frequencies can vary across subpopulations
what marks evolution of a population over time
changes in allele (genotype) frequency
proportion of chromosomes in a population carrying a particular allele at some locus
proportion of individuals in a population w/ a particular genotype at some locus
what does Hardy-Weinberg equilibrium state?
in a large population, allele frequency for autosomal traits will achieve and remain in a state of equilibirum after 1 generation of random mating
if you know the frequency of the allele in the population, you can estimate the frequence of the genotype in the population
what are population conditions for H-W equilibirum to work?
holds in a model population that's
1) infinitely large or large enough to neglect errors,
2) mating occurs randomly,
3) there's no advantage for any genotype,
5) no new mutations
what is the formula of the H-W equilibrium? name the varibles
p = allele A
q = allele a
p2 = homozygous genotype AA
q2 = homogous genotype aa
2pq = htereozygous genotype Aa
p+q = 1
p2 + 2pq + q2 = 1
what does H-W say about allele frequencies?
allelic frequencies will remain constant over time if certain conditions are met:
absence of distributing forces like migration, mutation, and selection in a given gene
what can cause deviation from H-W equilibrium expected frequencies?
1) genotyping errors
3) genetic drift
4) non-random mating
5) population structure
why does natural selection occur? what does it cause?
drives evolution of adaptive traits
occurs as result of fact that more organisms can survive and reproduce
thus selection, propagation, reproduction of genotypes that confer enhanced ability to survive and reproduce
if an allele confers ability to survive, it is reproduced over time
does natural selection work w/ H-W equilibrium
are humans exempt from natural selection?
think - 30% of pregnancies end by spontaneous abortion of embryos & fetuses, = mortality selection
& of those who marry, ~10% won't have children, = fecundity selection
what is genetic drift?
in each generation, some individuals may by chance leave behind a few more descendents (& genes) than others
genes of next generation will be genes of those "lucky" individuals, not the healthier/"better" individuals
happens to all populations
is an entirely random process, unlike natural selection
does not produce adaptations
what are founder effects
genetic drift means population can have high frequency of a gene that causes disease, if its present in that population and there isnt mixing
what is stabilizing vs directional selection? what causes each?
selective pressures can act on traits to favor intermediate phenotypes, = stabilizing selection, and to discriinate against intermediate phenotypes, = disruptive selection, or to favor extreme phenotypes, = directional selection
how does natural selection in humans occur
mortality in utero
illnesses prior to sexual maturity
non-reproduction due to fertility problems or choice
what is birth weight an example of re: natural selection
extremes selected against
what's coat color an example of re: natural selection
intermediate coat color isnt as favorable as dark/light depending on environment, diurnal vs. nocturnal
what are domesticated animal habits an example of re: natural selection
speed can be adventageous - greyhound breeding
what is nonrandom mating
what does it cause
how does it occur
source of devaition from H-W in humans
occurs as result of assortative mating from non-random mate selection choices on bases of physical or cultural characteristics
inbreeding also results in positve assortative effects on gene pool
assortative mating means
people non-randomly choose their mates
based on size, cultural characteristics
what causes inbreeding
when does it occur
what is its effect on genotype
caused by restricted mobility often
more pronounced in small populations
high risk of recessive diseases
can cause evolution of subpopulations
if sample is drawn from 2 or more populations, what is effect on allele frequencies?
cannot apply H-W, which assumes samples came from single population
find higher-than-expected homozygosity
can create false-positive associations
what does "out of africa" hypothesis say about allele frequencies
original population's hoogeneous genome has changed to migrated population's genome
due to adaptations as moved across world to: environmental effects, nutritional changes, cultural adaptations
how does population stratification impact GWAS studies
source of error in GWAS
get unequal distribution of alleles in study pop. may result from
1) sample made up of more than 1 distinct population
2) sample made up of individuals w/ differening levels of admixture
if cases and controls in GWAS aren't well matched ancestrally, what can happen?
1) unequal distribution of non-disease-related alleles btwn cases & controls
2) any allele more common in population w/ increased risk of disease may appear to be associated w/ disease
what is an AIM?
polymorphisms that exhibit substantially diff frequencies btwn populations from diff geographical regions
can use AIMS to estimate the geographical origins of the ancestors of an individual, determine what proportion of ancestry is derived from each geographical region
15 million SNPs from which AIMs can be selected
what does the int'l HapMap show
SNPs are not inherited individually; rather, correlate w/ each other & are inherited in blocks
what is linkage disequilibrium
the non-random association of alleles at 2 or more loci
aka 2 SNPs being inherited together rather than independently
measured on scale of 0 to 1
what are the measures for LD
D' and r2
r2 is correlation btwn SNPs, preferred measure
when D' and r2 >0.8, 2 SNPs are in LD and typing 1 SNP provides info on other SNPs
if D' and r2 = 0, typing 1 SNP provides no info on the other SNP
what is association between newness of a population and haplotide blocks?
newer population = longer hap blocks (higher LD)
older population (african) = shorter hap blocks (lower LD) - have the least homogeneity
must all SNPs be tested in GWAS?
variation is inherited in groups/blocks
so can test SNPs by tagging SNPs, impute missing genotypes from neighboring SNPs