L9 Molecular Population Genetics 2

Question 1

Factors affecting LD

Answer 1

mutation, drift, limited recombination, demographic effects e,g, admixture, bottlenecks

There is LD between closely linked sites but no LD between distant sites as recombination has broken them up

Question 2

Admixture

Answer 2

The mixing of two genetically differentiated populations

Initially LD will be proportional to allele freq. differences between the two populations and is unrelated to the distance between markers

Question 3

Extended LD

Answer 3

Dependent on migration rate and recombination rate

Question 4

Five matings for moderns, Neanderthals

Answer 4

See OneNote

Question 5

LD - selective sweeps

Answer 5

See OneNote for diagram

• LD can show which parts of the genome shows selection
• selective sweeps for advantageous mutations can lead all the way to fixation
• Selective sweep leaves certain footprints: No variation

Question 6

Reduction in genetic diversity as a consequence of selective sweep

Answer 6

See OneNote diagram
e.g 9 sites with no variation, sign of strong selective sweep
If demographic event, we might see signal across the whole genome

Limitations:
the wide the sweep, the easier to detect but the hard to identify THE selected site

Question 7

Selective sweep - Tajimas D

Answer 7

See OneNote diragram

If selective sweep, expect local excess of rare sites

Mutations arise over time, takes a while for it to drift away => more rare sites

In humans, it takes about 1MY for a neutral mutation to be fixed

Question 8

FOXP2

Answer 8

See OneNote

• gene associated with speech and language
• gene is highly conserved suggests lots of purifying selection acting on it
• 2 aa changes but within humans there is a skew towards rare site, suggest selective sweep
• Regions of human genome without denisovan or neanderthal genome - shown in pink, that is where the FOXP2 is

Question 9

Signs of a selective sweep - footprint

Answer 9

See OneNote

Left in the patterns of the nucleotide polymorphism:

1. locally reduced heterozygosity
2. skewed frequency spectrum
3. Increased LD/haplotypes

From the footprint you can infer:

• how recent?
• how strong was the selective agent?

Question 10

Macpherson diagram 2007

Answer 10

See Macpherson 2007 diagram on OneNote

Question 11

CCRDELTA32

Answer 11

Case study
See OneNote
- estimate age of a variant by the length of the haplotype it occurs on
- allele with 32 nucleotide deletion provides some protection against AIDS
- rise of mutation to 13% in caucasians in 27 generations not due to positive selection, ancient DNA says the allele is older. Subsequent analysis of hapmap SNP data suggests demographic effect rather than a sweep

Question 12

To age a new allele

Answer 12

• We assume the probability that a haplotype remains intact (P) equals the proportion of the original haplotype in current populations

P=(1-c)^G

Question 13

Hard sweep

Answer 13

single variant goes to fixation

the higher the integrative haplotype score, the stronger the selective sweep

Question 14

Lactase - selective sweep

Answer 14

• Lactase region shows strong selective sweep in Europeans

- Lactase region has a very long haplotype