Genetic drift + fixation, F statistics, Linkage Disequilibrium, and Applied Population genetics

Question 1

Neutral theory of molecular evolution

Answer 1

Most genetic variation is selectively neutral, so most molecular evolution is due to drift

Question 2

Effect of population size on fixation

Answer 2

Genetic drift is much greater in small populations. It takes much longer for an allele to reach fixation in larger populations

Question 3

What is the initial frequency of mutation

Answer 3

1/2N, where N = population size

Question 4

What is the probability of fixation

Answer 4

1/2N

Question 5

What is the probability of extinction

Answer 5

1-1/2N

Question 6

What is the rate of mutation in POPULATION?

Answer 6

2Nu

Question 7

What is the overall rate of neutral evolution?

Answer 7

rate of mutation in a population x probability of fixation for that mutation

2Nu x 1/2N

Question 8

Nearly-neutral theory of molecular evolution

Answer 8

Acknowledges that many if not all alleles might have a selective advantage/disadvantage

Question 9

Founder effect

Answer 9

Loss of genetic diversity when new population is founded

Question 10

Population bottleneck

Answer 10

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

Question 11

What do F statistics tell us?

Answer 11

Genetic variation within and between populations

Question 12

What is Fst?

Answer 12

Proportion of genetic variation accounted for by differences between sub-populations

Question 13

What is Fis?

Answer 13

Differences between individual and sub-populations

Question 14

What does a high Fst indicate?

Answer 14

Large proportion of genetic differences amongst individuals is because of population structure (more than 1 sub-population)

Question 15

Mendel’s law of independent assortment

Answer 15

Alleles for independent traits segregate independently into gametes

Question 16

What is linkage disequilibrium?

Answer 16

Non-random association of alleles at a pair of genetic loci

Question 17

Haplotype

Answer 17

Combination of alleles at adjacent sites on a chromosome that tend to be inherited together

Question 18

Linkage disequilibrium equation

Answer 18

Dab = Pab - PaPb

Question 19

What is D’ in linkage disequilibrium?

Answer 19

Normalised deviation from haplotype frequency from linkage equilibrium
Range = -1 to 1
If -1 or 1 = no evidence of recombination between alleles

Question 20

What is r^2 in linkage disequilibrium?

Answer 20

Statistical correlation between alleles
range = 0 to 1
If 1 = perfect correlation between alleles

Question 21

What is liability in GWAS

Answer 21

Accumulative burden of genetic risk that we carry for a disease

Question 22

What is the threshold for GWAS?

Answer 22

5 x 10^-8

Question 23

What is the Bonferroni-corrected p-value threshold?

Answer 23

0.05/number of SNPs

Question 24

The 7 steps of the PCA algorithm

Answer 24

1. Start with n-dimensional data
2. Find a rotation in d dimensions that defines a new axis that captures the most variance in the data
3. Call this axis (PC1)
4. Fixing this axis, find a rotation orthogonal (at right angles in remaining dimennsions) to PC1 that captures the second-most variance in the data
5. Call this axis (PC2)
6. Repeat steps 4 and 5 for all remaining dimensions
7. Plot Pcs of interest (usually 1 and 2 )