25. Population differences could have non-genetic basis • Differences due to environment? (Idaghdour et al. 2008) • Differences in cell line preparation? (Stranger et al. 2007) • Differences due to batch effects? (Akey et al. 2007) (Reviewed in Gilad et al. 2008) Slide courtesy Alkes Price
26. Gene expression experiment Does gene expression in 60 CEU + 60 YRI vary with ancestry? Does gene expression in 89 AA vary with % Eur ancestry? 60 CEU + 60 YRI from HapMap, 89 AA from Coriell HD100AA Gene expression measurements at 4,197 genes obtained using Affymetrix Focus array c Slide courtesy Alkes Price
27. Gene expression differences in African Americans validate CEU-YRI differences c = 0.43 (± 0.02) ( P -value < 10 -25 ) 12% ± 3% in cis Slide courtesy Alkes Price
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31. IRGM harbors a 20-kilobase deletion polymorphism immediately upstream IRGM Individuals Position on chr5 Slide courtesy Steve McCarroll McCarroll et al., Nature Genetics , Sept. 2008 rs13361189 (strongest Crohn’s-associated SNP)
32. IRGM structural haplotypes have altered expression Slide adapted, courtesy Steve McCarroll McCarroll et al., Nature Genetics , Sept. 2008
33. IRGM expression levels influence the efficacy of autophagy McCarroll et al., Nature Genetics , Sept. 2008 Slide adapted, courtesy Steve McCarroll