Recombinant mapping of the familial hyperinsulinism gene to an 0.8 cM region on chromosome 11p15.1 and demonstration of a founder effect in Ashkenazi Jews

Abstract

A gene for autosomal recessive familial hyperinsulinism (HI) (OMIM: 256450), a neonatal metabolic disease characterized by inappropriate insulin secretion In the presence of severe hypoglycemia, was recently mapped to a 6.6 cM interval between the markers D11S926 and D11S928 on chromosome lip In 15 families (1). in the current study we evaluated six additional families and five new markers, and further localized the gene between D11S419 and D11S131O. Using genotype data from CEPH Version 7 and data generated from this study, this region was estimated to be 0.8 cM in length. Significant linkage disequilib rium between markers and the HI gene was observed over a region of 10.3 cM (11pter-D11S926-D11S1308-11pcen) for Ashkenazi Jewish chromosomes. Haplotype analysis showed that 12 of 36 HI chromosomes, versus one of 36 non-HI chromo somes, bore a specific haplotype for D11S419-D11 S902-D11 S921 (p<0.0007), strongly suggesting a founder eftect In this ethnic group.