Broad Institute/MPG primer lecture given 2008-12-11. Thanks to Alkes Price and Steve McCarroll for contributing slides.

8. Definitions Cis Trans

13. Trans hotspots Brem et al Science 2002

14. Yvert et al Nat Genet 2003

16. Mammals II Chesler et al Nat Genet 2005 10% !!

22. Correlation networks persist across tissues

24. Slide courtesy Alkes Price

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

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