population genetics Flashcards
How DNA is variable between 2 individuals
any 2 copies of the human genome are 99.9% identicle in sequence, the majority of differences are SNPs or indels and other structural variations. Polymorphisms are allelic. 3 million SNPs between any two people, but more in some populations and less in other
mutation rates
mutageneisis, mostly cause the replication process happens every 1/100million bp
Every gamete contains 10-100 de novo mutations. Somatic mutagenisis happens all the time but those are not transmitted to offspring, only germline mutations are transmitted (but even then only 50% of germline mutations are transmitted)
longer genes have more mutations. Mutation hot spots like CpG s (c->uracil deamination)
Mutation vs polymorphisms
Mutation (de novo) occurs in less than 1% of the population: usually a varient that results in altered function of the protein, all SNPs initially occur as mutation
Polymorphisms: is present in more than 1% SNP
Linked SNP: no effect on protein but the SNPs are linked to disease
Causitive SNPs: noncoding (but in regulatory region, affect amount of protein made). Coding (synonomous or non synnomous– alter AA sequence
How allelic frequency change
When a mutation become >1% in frequency there is typically no selective pressure. The major driving force for increase/decrease of allelic frequency is genetic drift- just by chance expansion or dissapearance. After lots of generations, most SNPs show two common alleles with the minor allel in the 10-20%
genetic drift vs selection
genetic drift: is a random process where some mutation arise where others disappear. The smaller the pop, the more variabilty in frequency
selection: when the mutation affects reproductive fitness
Positive selection: mutation is more likely to become a SNP if the mutation increases reproductive success
Negative selection: allele isnt transmitted, rarely completely removes an allele bc heterozygotes live. If the mutation is age dependent (alzheimers)– neg selection wont do anything cause the people can still reproduce
migration and inbreeding
migration: gene flow mating between two sub populations. (change in allel frequency is influenced by the size of pop)
inbreeding: mating of close releative-> decrease in variation within populaiton causing change in frequency dramatically
hardy weinberg equation
HW model describes and predicts genotype and allele frequency in a non evolving population
if no evolution is occuring then an equilibrium of allel frequency will remain in effect in each succescive generation of randomly mating individuas
HW assumptions: in order to remain in effect (no evolution is occuring): no mutations, no geneflow, random mating, large population to avoid genetic drift, no selection
P= f(A/A) + 1/2 f (A/a)= frequency of A
Q= f(a/a) + 1/2 (A/a)= frequency of a
p+q=1 in first generation
in susequent generations: p^2= f(A/A) 2pq= f (A/a) q^2= f (a/a) p2 + 2pq +q2= 1
if observed doesnt match the HW
if observed numbers and frequencies are not what are expected in the next gen, then use a chi squared
df the number of possible alleles minus one = 2-1= 1
Chi2= sum (o-e)2/ e
if its greater then the table value then its not in HW equilibrium
sickle cell is not in HW equilibrium bc it imparts malaria resistance
linkage analysis
alleles that are close to each other will be inherited together
genetic markers and recombination
a known position on a gene that are known tracks a disease. recombination between 2 markers depends on distance. if two DNA are far apart the chances for recombination is 50/50 (independent). if they are very close then its less likely recombination will work (1 cm= 1% recombination=1 million bp)
linkage disequilibrium
non random association of SNP alelles at closely linked loci and these alleles are frequently coinheited and are in linkage disequilibrium
