1. Worldwide population differentiation at
disease associated SNPs
Hong Chang Bum
Center for Genome Science, NIH, KCDC

4. Characterizing signals
of selection in humans

5. Jomon , , (2 )
- ( ), (
)
Seto Inland Sea
Yayoi
2,000 ,
Super Science High School(SSH)
48 55 (48 SSH + 7 ), 5 , 1,963

6. rs17822931(ABCC11)
GG Wet earwax
GA Wet earwax
AA Dry earwax
G Ancestral allele A derived allele

7. My Japanese Friends

8. Worldwide population differentiation at
disease-associated SNPs
~1000 individuals from 53 population, 25 SNPs
6 complex human diseases

9. 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

10. ALFRED(The Allele Frequency Database)
HapMap
Allele frequency resources
- lactose tolerance, lactase(LCT) gene

11. Haplotter - iHS, detect selective sweeps
Selection resources(lactose tolerance,
lactase(LCT) gene)
- iHS

12. HGDP Selection Browse
Selection Resources (thicker hair, EDAR
gene)
- Fst, iHS, XP-EHH, allele frequency

13. East Asia(red haplotype under selection) Middle East(no strong recent selection)
Selection Resources (thicker hair, EDAR
gene)
- expanded haplotype plots

14. 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
.

16. replication, large
number of population

17. 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.

20. rs13266634, T2D
Africa: 0.941
Oceania: 0.911
rs1801281, T2D
Africa: 1
Oceania: 1
rs564398, T2D
Africa: 1
America: 0.937

21. Global Fst
provides a
rough measure
of the
magnitude of
allele frequency
differentiation
worldwide
mean global
Fst

27. Thank You!
@hongiiv
http://
hongiiv.tistory.com
HONGII
V
Open Bioinformatics