Linkage analysis of the human insulin receptor gene and maturity onset diabetes of the young.

The cloning of the insulin receptor cDNA has permitted the definition of restriction fragment length polymorphisms at that locus. These polymorphisms were used to study the role of the insulin receptor in four pedigrees with maturity onset diabetes of the young through linkage analyses. When each pedigree was individually analysed, no linkage was demonstrated in the two larger pedigrees, implying that an insulin receptor defect was not responsible for the predisposition to diabetes in these pedigrees. One of these pedigrees was known to be hypoinsulinaemic, while insulin levels were unavailable in the second pedigree. In the two smaller pedigrees, however, a single haplotype cosegregated with diabetes. One of these pedigrees is known to be hyperinsulinaemic. The small size of the pedigrees which demonstrated cosegregation precluded statistical proof of linkage. Nonetheless, the presence of an uncommon insertional polymorphism which cosegregated with diabetes in both pedigrees was improbable and suggested that this insertion could be responsible for diabetes in these families. This study thus may be additional evidence for heterogeneity in maturity onset diabetes of the young. For the two larger pedigrees, the insulin gene and HLA region have already been eliminated as genetic markers. This study provides data which eliminate a third candidate gene in these two pedigrees.