A high-resolution 6.0-megabase transcript map of the type 2 diabetes susceptibility region on human chromosome 20

Recent linkage studies and association analyses indicate the presence of at least one type 2 diabetes susceptibility gene in human chromosome region 2 0q12-q13.1. We have constructed a high-resolution 6.0-megabase (Mb) transcr ipt map of this interval using two parallel, complementary strategies to co nstruct the map. We assembled a series of bacterial artificial chromosome ( BAC) contigs from 56 overlapping BAC clones, using STS/marker screening of 42 genes, 43 ESTs, 38 STSs, 22 polymorphic, and 3 BAC end sequence markers. We performed map assembly with GraphMap, a software program that uses a gr eedy path searching algorithm, supplemented with local heuristics. We ancho red the resulting BAC contigs and oriented them within a yeast artificial c hromosome (YAC) scaffold by observing the retention patterns of shared mark ers in a panel of 21 YAC clones. Concurrently, we assembled a sequence-base d map from genomic sequence data released by the Human Genome Project, usin g a seed-and-walk approach. The map currently provides near-continuous cove rage between SGC32867 and WI-17676 (similar to 6.0 Mb). EST database search es and genomic sequence alignments of ESTs, mRNAs, and UniGene clusters ena bled the annotation of the sequence interval with experimentally confirmed and putative transcripts. We have begun to systematically evaluate candidat e genes and novel ESTs within the transcript map framework. So far, however , we have found no statistically significant evidence of functional allelic variants associated with type 2 diabetes. The combination of the BAC trans cript map, YAC-to-BAC scaffold, and reference Human Genome Project sequence provides a powerful integrated resource for future genomic analysis of thi s region.