1 / 54

Population Genetics

Population Genetics. Population Genetics. ...or “what processes led to the data we’re analysing?”. Imagine we collect and sequence some samples. ATAGAAAGACCAGACTCCATCGCTAGCAGCTACGCTAGAGTTA. N samples. ATTGAAAGACCATACTCCATCGCTAGCAGC-ACGCTAGAGTTA. ATAGAAAGACCAGACTCCATCGCAAGCAGC-ACCCTAGCGTTA.

theresanichols
Télécharger la présentation

Population Genetics

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Population Genetics

  2. Population Genetics ...or “what processes led to the data we’re analysing?”

  3. Imagine we collect and sequence some samples... ATAGAAAGACCAGACTCCATCGCTAGCAGCTACGCTAGAGTTA N samples ATTGAAAGACCATACTCCATCGCTAGCAGC-ACGCTAGAGTTA ATAGAAAGACCAGACTCCATCGCAAGCAGC-ACCCTAGCGTTA ATAGAAAGACCAGACTCCATCGCAAGCAGCTACGCTAGAGTTA . . .

  4. Imagine we collect and sequence some samples... Reference sequence ATAGATAGACCATACTGCATCGCAAGCAGCTACGCTAGCGTTA ATAGAAAGACCAGACTCCATCGCTAGCAGCTACGCTAGAGTTA ATTGAAAGACCATACTCCATCGCTAGCAGC-ACGCTAGAGTTA ATAGAAAGACCAGACTCCATCGCAAGCAGC-ACCCTAGCGTTA ATAGAAAGACCAGACTCCATCGCAAGCAGCTACGCTAGAGTTA

  5. Imagine we collect and sequence some samples... ATAGATAGACCATACTGCATCGCAAGCAGCTACGCTAGCGTTA .....A......G...C......T..............A.... ..T.............C......T......-.......A.... .....A......G...C.............-..C......... .....A......G...C.....................A.... Insertion / deletion polymorphism SNPs

  6. Outline Population genetic processes Measuring correlations between alleles Recombination Differences between populations

  7. Genetic variation ATAGATAGACCATACTGCATCGCAAGCAGCTACGCTAGCGTTA .....A......G...C......T..............A.... ..T.............C......T......-.......A.... .....A......G...C.............-..C......... .....A......G...C.....................A.... ...or, in cartoon form:

  8. Genetic variation Two chromosomes (= haplotypes) carried by each individual

  9. 24 haplotypes (12 individuals) 100 SNPs on chromosome 20 Utah residents, ancestrally Northern and Western European Yoruba from Ibadan, Nigeria

  10. Population genetic processes • Genetic drift • Mutation • Recombination • Natural selection • It is the combination of these fundamental processes that generate diversity within a population

  11. Genetic Drift current generation N N-1 N-2 ... population

  12. Genetic Drift current generation

  13. Genetic Drift current generation

  14. Genetic drift current generation N generations ago . . . . . . Genetic drift creates correlations between alleles

  15. Recombination Paternal (father) Maternal (mother) Recombination No recombination

  16. Recombination . . . . . . Recombination breaks down the correlation between alleles

  17. Thinking backwards in time • As chromosome are passed from one generation to the next patterns of diversity evolve • When we take data from the present we need to think about the past. • What are the ancestral processes that generated the data?

  18. Ancestral history Present day

  19. Ancestry of the population Present day

  20. Ancestry of sample Present day

  21. Ancestry of sample The probability that two chromosomes share a common ancestor in the previous generation is 1/2N

  22. Ancestral processes Mutation Recombination Coalesce 2μ 2r 1/2N If two chromosome coalesce before they incur a mutation or recombination event then they will be identical

  23. Genetic diversity The probability that two individuals share a common ancestor in the previous generation is 1/2N The expected time to two individuals coalesce is 2N The probability two chromosomes are identical (by descent) is:

  24. Large and small ancestral populations • In large populations we have to go further back in time to time to find the common ancestor • Consequently there is more opportunity for • Mutation, increasing genetic diversity • Recombination, decreasing correlation between alleles

  25. Human population history The recent migration of European from Africa has lead to small effective population sizes

  26. 24 haplotypes (12 individuals) 100 SNPs on chromosome 20 Utah residents, ancestrally Northern and Western Europe Yoruba from Ibadan, Nigeria

  27. Natural Selection When a beneficial mutation arises it spreads quickly through the population generating strong correlations between alleles

  28. Natural Selection Big differences in the patterns of diversity between populations can be generated by natural selection

  29. Differences between populations Big differences in the patterns of diversity between populations can be generated by natural selection

  30. Population genetics • Genetic drift generates correlations between alleles • Recombination breaks them down • The ancestral population size and history determines the amount of diversity and how it is structured • Natural selection can generate strong differences between populations

  31. Measuring correlations • In genetics correlation between alleles is called linkage disequilibrium (LD) • There are several measures of LD • Understanding LD in natural populations is important for genomic epidemiology

  32. Linkage equilibrium A B AB Ab a b ab aB Haplotype frequencies are determined by SNP allele frequencies (they are in equilibrium)

  33. Linkage disequilibrium AB Ab aB ab Haplotype frequencies differ from those expected if the SNPs are independent (they are in disequilibrium)

  34. Measuring LD D ≈ 0 when near linkage equilibrium D ≠ 0 when there is linkage disequilibrium Two measures

  35. Haplotypes and LD 1 2 3 4 r2 is less than one unless SNP A is a perfect surrogate of SNP B in the sample D’ statistic less than one if and only if all four haplotypes are present in sample So D’ is 1 unless visible recombination has occurred

  36. Recombination and physical distance r2=1 r2=0.9 r2=0.5 r2=0.1 Correlations decay with distance (due to recombination)

  37. Looking at patterns of LD High r2 Low r2 Assume similar physical spacing LD patterns are complicated

  38. Recombination clusters along chromosomes Studies have shown that recombination is not uniform along chromosomes

  39. Recombination hotspots Recombination hotspots occur through out the genome

  40. Hotspots and haplotypes Hotspots can break down correlations over short distances

  41. Hotspots and haplotypes Recombination hotspots lead to regions of strong correlation separated by regions of low LD

  42. LD and Recombination • There are lots of ways to measure LD • Recombination is not uniform along chromosomes • Much of the recombination happens in hotspots and these demark breakdown in correlations • Correlations do persist across hot spots

  43. Differences between populations The overall pattern of LD is conserved The different ancestral histories lead to different levels of LD

  44. Differences between populations The overall pattern of LD is conserved The different ancestral histories lead to different levels of LD

  45. Population structure in Africa There is evidence for widespread population structure across Africa

  46. Population structure in Africa Add population differences between groups from the same region

  47. 24 haplotypes (12 individuals) 100 SNPs on chromosome 20 Luhya in Webuye, Kenya Maasai in Kinyawa, Kenya

  48. Differences in patterns of LD • An experiment: • Take genome-wide SNP data collected from a European population (A) • Take each SNP and find the SNPs which is most correlated with it (and remember how correlated it is) • Go to another European population (B) and compare the correlation between the two SNPs in the new population • (Measure correlation as r2)

  49. Differences in patterns of LD Across Europe Within Kenya We will look at this in the practical

  50. Summary • Different ancestral histories have led to different patterns of diversity • Natural selection can generate strong differences in haplotype patterns • Population structure across Africa, and between groups in Africa, will lead to differences in the structure of LD

More Related