Figure 1.

A common, 20-kb deletion polymorphism upstream of IRGM.

(a) Hybridization of DNA from 90 HapMap YRI samples to the Affymetrix SNP 6.0 array reveals a correlated pattern of variation in intensity across six copy-number probes spanning the region upstream of IRGM, suggesting the existence of a common copy-number polymorphism. (Darker shades of red represent reduced hybridization intensity.) Quantitative PCR indicated that the copy-number-variable region was an insertion/deletion (Supplementary Fig. 1). (b) Mapping of the deletion breakpoints by microarray and PCR. Red indicates evidence for deletion; black indicates evidence to the contrary; blue arrows indicate locations of flanking PCR primers able to generate a PCR product in individuals with at least one deletion allele. (c) Sequence of the reference and deletion alleles. The CD-associated SNP rs13361189 is indicated in boldface red type. Physical coordinates are on the reference human genome (build 35/36); allele frequencies are for extended HapMap analysis panels, including 540 samples. (d) CD association of typed and imputed polymorphisms in the IRGM region in the NIDDK IBDGC genome scan⁵,⁸. Blue trace indicates recombination map. The deletion polymorphism and rs13361189 are indicated by red arrows. rs13361189 (which is in perfect linkage disequilibrium with the deletion, r² = 1.0) was also the most strongly associated SNP in the combined WTCCC genome scan and replication study².