Genetic drift + fixation, F statistics, Linkage Disequilibrium, and Applied Population genetics Flashcards
Neutral theory of molecular evolution
Most genetic variation is selectively neutral, so most molecular evolution is due to drift
Effect of population size on fixation
Genetic drift is much greater in small populations. It takes much longer for an allele to reach fixation in larger populations
What is the initial frequency of mutation
1/2N, where N = population size
What is the probability of fixation
1/2N
What is the probability of extinction
1-1/2N
What is the rate of mutation in POPULATION?
2Nu
What is the overall rate of neutral evolution?
rate of mutation in a population x probability of fixation for that mutation
2Nu x 1/2N
Nearly-neutral theory of molecular evolution
Acknowledges that many if not all alleles might have a selective advantage/disadvantage
Founder effect
Loss of genetic diversity when new population is founded
Population bottleneck
Loss of genetic diversity when population size is dramatically reduced. Sometimes a natural disaster can create selection pressure rendering some alleles more likely to survive - oftentimes just random event
What do F statistics tell us?
Genetic variation within and between populations
What is Fst?
Proportion of genetic variation accounted for by differences between sub-populations
What is Fis?
Differences between individual and sub-populations
What does a high Fst indicate?
Large proportion of genetic differences amongst individuals is because of population structure (more than 1 sub-population)
Mendel’s law of independent assortment
Alleles for independent traits segregate independently into gametes
What is linkage disequilibrium?
Non-random association of alleles at a pair of genetic loci
Haplotype
Combination of alleles at adjacent sites on a chromosome that tend to be inherited together
Linkage disequilibrium equation
Dab = Pab - PaPb
What is D’ in linkage disequilibrium?
Normalised deviation from haplotype frequency from linkage equilibrium
Range = -1 to 1
If -1 or 1 = no evidence of recombination between alleles
What is r^2 in linkage disequilibrium?
Statistical correlation between alleles
range = 0 to 1
If 1 = perfect correlation between alleles
What is liability in GWAS
Accumulative burden of genetic risk that we carry for a disease
What is the threshold for GWAS?
5 x 10^-8
What is the Bonferroni-corrected p-value threshold?
0.05/number of SNPs
The 7 steps of the PCA algorithm
- Start with n-dimensional data
- Find a rotation in d dimensions that defines a new axis that captures the most variance in the data
- Call this axis (PC1)
- Fixing this axis, find a rotation orthogonal (at right angles in remaining dimennsions) to PC1 that captures the second-most variance in the data
- Call this axis (PC2)
- Repeat steps 4 and 5 for all remaining dimensions
- Plot Pcs of interest (usually 1 and 2 )
