Linkage Analysis of Maturity-Onset Diabetes of the Young With Microsatellite Polymorphisms: No Linkage to ADA or GLUT2 Genes in Two Families

MODY is a form of NIDDM inherited as an autosomal dominant condition. We studied the linkage of MODY to two loci: ADA and GLUT2 in two large pedigrees with nonradioactive microsatellite polymorphic systems. A positive linkage of ADA to MODY was recently demonstrated in the large RW pedigree. Formal linkage analysis excluded a tight linkage between ADA and MODY with a LOD score of −5.82 and −2.24 at a recombination fraction of 0.01 in the two families. This result suggests genetic heterogeneity in the molecular basis of MODY. GLUT2 is a candidate gene that is expressed in the liver and β-cells of pancreatic islets. In the two families studied, the disease did not cosegregate with GLUT2 alleles. The LOD scores for GLUT2 were −7.79 and −1.9 at a recombination fraction of 0.001 in the two families, thus providing evidence against the involvement of GLUT2 in MODY.