We are conducting a total genomic search for genes predisposing to type II diabetes on a Finnish population of affected sib-pairs and their immediate relatives. A set of fluorescently-labelled microsatellites which together give a 10cM resolution map of the human genome is being typed on approximately (a) 550 affected sib-pairs, (b) 200 non-affected spouses of an affected sib and (c) 500 offspring of these parents along with (d) 100 controls. This strategy allows us to perform discrete (diabetes) and quantitative trait linkage analysis (insulin resistance, beta cell function) along with linkage disequilibrium studies to narrow down the intervals thought to contain the disease genes. We have devised a database with programs that can filter and store editings of the data, adjust for intergel variation in sizes of microsatellite products, automatically bin alleles and provide output formats suitable for statistical packages in order to analyse the data. We are now in the process of completing chromosome 1 and are beginning to analyse chromosome 7. Our throughput is approximately 6000 genotypes a week but we hope to increase this substantially with automation in the near future. We are also conducting a candidate gene analysis on our data set for the alpha3 adrenergic receptor gene and hope to continue to look at other interesting candidates during our scan.
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