IRGM locus variation and putative isoforms. (A) A large insertion/deletion polymorphism exists upstream of the IRGM locus; linkage between the deletion and CD-risk SNPs suggest this polymorphism may be causal for the IRGM SNP-associated CD risk. An exonic SNP (T or C, as shown) in strong linkage disequilibrium with this deletion allows unambiguous identification of transcripts resulting from the risk or protective alleles. (B) There are five putative IRGM isoforms, although it is unclear which result in mature proteins. Putative mature mRNAs are shown; all isoforms are thought to share a common start codon, and untranslated exons and ORFs are shown in alternating shading to delineate intron/exon boundaries. Isoforms (c–e) all have intron-exon boundaries after the stop codon, usually indicative of targets for nonsense-mediated decay. All isoforms except (a) possess a putative second translated exon encoded on the genome approximately 30 kb downstream of the first exon, subsequent intron/exon boundaries are an additional 17 to 20 kb distant.