Lecture 9

Question 1

Selective sweeps:

4

Answer 1

• The reduction or elimination of genetic variation among nucleotides of neighbouring DNA of a mutation as a result of recent and strong positive natural selection
• Reduction in polymorphisms
• Increase in extent of LD, longer haplotypes
• The wider the sweep the easier to detect, but the harder to identify the selected site

Question 2

Why is expected and observed heterozygosity so different?

2

Answer 2

• Population size fluctuation

- Genetic hitchhiking

Question 3

After a selective sweep we would expect

2

Answer 3

• An excess of singletons

- Negative TD around sites

Question 4

FOXP2 gene:

2

Answer 4

• Associated with speech and language

- Mutations are associated with seder articulation problems, linguistic and grammatical impairment

Question 5

Comparison of the FOXP2 in humans and other primates showed..
(3)

Answer 5

• 2/0
• 2 amino acid changes in the FOXP2 gene
• Selection was acting on this gene

Question 6

Selective sweeps cause changes in the patterns of nucleotide polymorphisms:
(3)

Answer 6

• Locally reduced heterozygosity
• Increase LD/haplotypes
• Skewed frequency spectrum

Question 7

From the footprint caused by selective sweeps we can infer..

2

Answer 7

• How recent was this selection (depth of point)?

- How long ago was this selection (width of trough)?

Question 8

CCR5 gene in humans:

4

Answer 8

• An allele variant called CCR5delta32 (a 32bp deletion)
• Expressed on some immune cells, chemokine receptor 5, found on T-cells, and other cells of the immune system
• HIV uses it as a receptor
• An allele with a 32 bp deletion provides some protection against AIDS, as it takes longer to bind

Question 9

CCR5 haplotypes observed in modern caucasians:

3

Answer 9

• A number of haplotypes are represented in different numbers across individuals
• delta32-197-215 for CCR5-GAAT-AFMB haplotype is at 84.8% of the population
• The delta32 haplotype probably arose in a 197-215 background

Question 10

The probability that a haplotype remains intact (P) equals

2

Answer 10

• The proportion of the original haloptype in current populations, using this formula
• P = (1-c) to the power of G = 84.8

Question 11

How long ago did the delta32 variant arise?

Answer 11

• Delta32 variant arose, 27 generations ago, generation time of 25 years, so arose about 700 years ago.
• This was incorrect.
• CCRG-delta32has much higher frequency in Caucasian populations that elsewhere and arose much much earlier, prior to the pressure of AIDS

Question 12

The real story of the CCR5delta32 variant

Answer 12

• Ancient DNA says the allele is older, and subsequent analysis of hap map SNP data
• Suggest demographic effect rather than a sweep

Question 13

Evidence for extended haplotypes in different populations highlights two genes:
(2)

Answer 13

• Lactase gene in european populations

- NCOA1 in Yoruba populations, involved in fatty acid regulations

Question 14

Using genomic to identify positive selections from oldest selection (6 million years) to current selection (25 thousand years)

Answer 14

• dN/dS: proportion of functional changes (or relative rate tests)
• Pi: heterozygostiy/rare alleles (deficit of variation in particular regions)
• Tajimus D: High frequency derived alleles
• Fst: Population differences
• iHS: length of haplotypes (over time they are broken down)