Type 2 diabetes is one of the major causes of morbidity and mortality in the developed world. While environmental factors such as diet play a significant role, familial clustering indicates that there must be significant genetic suscepibility factors at work. For nine years we have been engaged in a large collaborative study entitled FUSION (Finland - United States Investigation of NIDDM), in which over 5000 individuals with diabetes (and suitable controls) from Finland are being studied, using careful phenotyping of diabetes and diabetes associated traits, and genome-wide genetic linkage and association. During FY 2001 this project has made significant progress, shifting almost entirely from microsatellite analysis to fine mapping using the mass spectrometer for high throughput single nucleotide polymorphism (SNP) genotyping. We have further strengthened the evidence for a diabetes locus on chromosome 22q, narrowing this down to a few hundred kilobases and confirming the association in a West African sample set. For chromosomes 11q and 20q, where we have our strongest linkage signals in a genome-wide scan, we have generated high density SNP maps and discovered narrow areas that show association at the 0.001 to 0.0001 level. We are now focusing on genes in these intervals as possible diabetes susceptibility candidates.
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