We are continuing our total genome scan on 2502 Finnish individuals, including 532 families with at least 2 affected sibs, at a 10cM resolution to find the susceptibility genes for type II diabetes mellitus. We have completed over 300,000 post-processed genotypes and finished scanning chromosomes 1, 2, 7, 8, 15 and 16. Our throughput has doubled over the last year to an average of 12,000 per week. Our average error rate is in the region of 0.3%. Using multi-point linkage analysis with affected sib-pairs we have been able to exclude the D2S125 region at the telomeric portion of 2q at a lambdas value of 1.35 or more. This locus was linked to NIDDM in a sample of Mexican-Americans and has an estimated lambdas value of 1.37 (NIDDM1) under an additive model. Furthermore, we are looking at the 12q region for the NIDDM2 locus which showed significant linkage in a population from the Botnia region of Finland. At present we are working towards doubling our throughput by introducing multiplex PCR and using gels with increased lanes. In addition we are designing a database system in SYBASE to handle the 2500 extra samples which will arrive during the course of the next year. The latter samples will help us in fine mapping.
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