Type 2 diabetes locus on 12q15 - Further mapping and mutation screening oftwo candidate genes

We recently reported evidence of a novel type 2 diabetes locus placed on ch romosome 12q15 between markers D12S375 and D12S1684 (Diabetes 48:2246-2251, 1999). Four multigenerational families having logarithm of odds (LOD) scor es >1.0 in the original analysis were genotyped for 11 additional markers i n this interval to refine this mapping; this allowed us to narrow the linke d region to the interval between markers D12S1693 and D12S326. In a multipo int parametric analysis using the VITESSE software, the LOD score for linka ge at this location reached 3.1 in one of these families. This interval con tains the gene for protein tyrosine phosphatase receptor type R (PTPRR)-a p rotein that may be involved in both insulin secretion and action. After det ermining PTPRR exon-intron structure, we identified several polymorphisms i n this gene but no mutation segregating with diabetes. The search for mutat ions was also negative for carboxypeptidase M (CPM)-another candidate gene mapped to this region. In summary, our data provide further evidence for th e existence of a type 2 diabetes locus on chromosome 12q15. This locus, how ever, does not appear to correspond to the PTPRR or CPM, although a contrib ution of mutations in regulatory regions cannot be excluded at this time.