International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


GAJ Morris
University of Cambridge

Tomkies V, Kingsnorth AJ, Payne K, Lyons PA.
University of Cambridge

Linkage analysis of the Non-Obese Diabetic mouse (NOD) genome has revealed the location of several non-MHC genes involved in type 1 diabetes. The breeding of novel congenic mouse strains has confirmed that one of these, Idd9 on mouse chromosome 4 is a true locus. Subsequent subcongenic mapping has shown that the original effect is due to the interaction of at least three distinct loci, Idd9.1, Idd9.2 and Idd9.3.  An unexpected outcome of the subcongenic analysis was that removal of the proximal region of the original congenic segment led to a significant reduction in diabetes frequency, suggesting the presence of a diabetes susceptibility gene conferred by the B10 allele. Genotyping a panel of mice from a cross between NOD and B10.H2g7 with the microsatellite markers D4Mit82 and D4Mit28 put the interval size at 20.6cM. High resolution mapping using a panel of 18 microsatellite markers refined the interval to 15.2cM, between the microsatellite markers D4Mcg25 and D4Mit144. Based on the current draft of the mouse genome sequence D4Mcg25 and D4Mit144 are located at 63.9Mb and 90.2Mb respectively on mouse Chromosome 4. Additional microsatellite markers have been generated from the draft sequence and used to refine the boundaries of the congenic strain that define Idd9.4. This new mapping data places the proximal boundary of Idd9.4 at 74.5Mb and the distal boundary of Idd9.4 at 88Mb. At present 30 known and 20 novel genes map to this interval, of which the Ifna/b cluster at 86Mb represents the most likely candidate for Idd9.4.

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