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worldwide population

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worldwide population

  1. 1. Worldwide population differentiation at disease associated SNPs Hong Chang Bum Center for Genome Science, NIH, KCDC
  2. 2. Characterizing signals of selection in humans
  3. 3. Jomon , , (2 ) - ( ), ( ) Seto Inland Sea Yayoi 2,000 , Super Science High School(SSH) 48 55 (48 SSH + 7 ), 5 , 1,963
  4. 4. rs17822931(ABCC11) GG Wet earwax GA Wet earwax AA Dry earwax G Ancestral allele A derived allele
  5. 5. My Japanese Friends
  6. 6. Worldwide population differentiation at disease-associated SNPs ~1000 individuals from 53 population, 25 SNPs 6 complex human diseases
  7. 7. SNP 25 individual 952 population 53 (7 geographic regions) 6 complex human diseases Crohn’s disease Type 1 diabetes disease Type2 diabetes Rheumatoid arthritis Coronary artery disease Obesity HGDP-CEPH panel sample 1 KBioscience, KASPar empirical Fst distribution from 2,750 autosomal marker sample 2 previously typed in 927 individuals from the CEPH-HGDP panel
  8. 8. ALFRED(The Allele Frequency Database) HapMap Allele frequency resources - lactose tolerance, lactase(LCT) gene
  9. 9. Haplotter - iHS, detect selective sweeps Selection resources(lactose tolerance, lactase(LCT) gene) - iHS
  10. 10. HGDP Selection Browse Selection Resources (thicker hair, EDAR gene) - Fst, iHS, XP-EHH, allele frequency
  11. 11. East Asia(red haplotype under selection) Middle East(no strong recent selection) Selection Resources (thicker hair, EDAR gene) - expanded haplotype plots
  12. 12. common alleles in one population, not common in another population frequency of disease-associated alleles show “large heterogeneity between races” frequency of a risk allele discovered in one population is not always a strong predictor of the frequency of that risk allele in other populations CAD, T2D have been targets of positive natural selection local positive selection results in large allele frequency differences between population positively selected alleles tend to accumulate in the top tail of the Fst distribution allele positive selection .
  13. 13. replication, large number of population
  14. 14. 0 0.05 0.15 0.25 1 case 1. 0 <= Fst <= 0.05 ignore genetic differentiation case 2. 0.05 <= Fst < 0.15 genetic differentiation case 3. within 0.15 <= Fst E. Asia strong genetic differentiation 0.04 Africa within Europe Europe case 4. 0.147 0.02 0.25 <= Fst very strong genetic differentiation E. Asia. E. Asia within Europe Africa Africa 0.115 0.223 case 5. Jeju 0.05 1 = Fst Gyeongju high difference Fst perfect 0.018 between Korea and Jeju isolation 0.073 1 Source: Tishoff SA and Kidd KK.(2004). Nature Genetics Suplement 36:S21-27.
  15. 15. rs13266634, T2D Africa: 0.941 Oceania: 0.911 rs1801281, T2D Africa: 1 Oceania: 1 rs564398, T2D Africa: 1 America: 0.937
  16. 16. Global Fst provides a rough measure of the magnitude of allele frequency differentiation worldwide mean global Fst
  17. 17. Thank You! @hongiiv http:// hongiiv.tistory.com HONGII V Open Bioinformatics

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