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Flashcards in Lecture 9 Deck (14):

Selective sweeps:

- 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


Why is expected and observed heterozygosity so different?

- Population size fluctuation
- Genetic hitchhiking


After a selective sweep we would expect

- An excess of singletons
- Negative TD around sites


FOXP2 gene:

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


Comparison of the FOXP2 in humans and other primates showed..

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


Selective sweeps cause changes in the patterns of nucleotide polymorphisms:

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


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

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


CCR5 gene in humans:

- 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


CCR5 haplotypes observed in modern caucasians:

- 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


The probability that a haplotype remains intact (P) equals

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


How long ago did the delta32 variant arise?

- 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


The real story of the CCR5delta32 variant

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


Evidence for extended haplotypes in different populations highlights two genes:

- Lactase gene in european populations
- NCOA1 in Yoruba populations, involved in fatty acid regulations


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

- 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)