Family-based linkage scan in three pedigrees with extreme diabetes phenotypes

Project leaders

Mark Daly, Broad Institute, Massachusetts General Hospital
Leif Groop, Lund University

Project Overview

Two families from the Lund University collection were selected for study based on extreme early onset of disease and severity of phenotype, characteristics that may signify a Mendelian form of disease. Several affected members from each of these families were screened for mutations in the known MODY genes (get list of precisely which genes were screened from Leif) and none were found. The families in this screen were ascertained as follows:

Family B: Twenty-two individuals, many of whom developed diabetes before the age of 40 years (a “MODY”-like pedigree, but without linkage to known MODY genes).
Family C: Twenty individuals (17 of whom are used for the analysis), with clustering of type 2 diabetes and varying age at onset.

Results Summary

Families B and C: No maximal or genome-wide significant evidence of linkage was observed across these entire families or in more tightly linked sub-pedigrees. These data failed to provide evidence for new MODY-type genes that might explain the clustering of early-onset diabetes in these families (figures for family B and family C).