Linkage-disequilibrium mapping without genotyping

Genomic mismatch scanning (GMS) is a technique that enriches for regions of identity by descent (IBD) between two individuals without the need for genotyping or sequencing. Regions of IBD selected by GMS are mapped by hybridization to a microarray containing ordered clones of genomic DNA from chromosomes of interest. Here we demonstrate the feasibility and efficacy of this form of linkage-mapping, using congenital hyperinsulinism (HI), an autosomal recessive disease, whose relatively high frequency in Ashkenazi Jews suggests a founder effect. The gene responsible (SUR1) encodes the sulfonylurea receptor, which maps to chromosome 11p15.1. We show that the combination of CMS and hybridization of IBD products to a chromosome-11 microarray correctly maps the HI gene to a 2-Mb region, thereby demonstrating linkage-disequilibrium mapping without genotyping.