Journal article
A recombination hotspot leads to sequence variability within a novel gene (AK005651) and contributes to type 1 diabetes susceptibility
IKL Tan, L Mackin, N Wang, AT Papenfuss, CM Elso, MP Ashton, F Quirk, B Phipson, M Bahlo, TP Speed, GK Smyth, G Morahan, TC Brodnicki
Genome Research | COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT | Published : 2010
Abstract
More than 25 loci have been linked to type 1 diabetes (T1D) in the nonobese diabetic (NOD) mouse, but identification of the underlying genes remains challenging. We describe here the positional cloning of a T1D susceptibility locus, Idd11, located on mouse chromosome 4. Sequence analysis of a series of congenic NOD mouse strains over a critical 6.9-kb interval in these mice and in 25 inbred strains identified several haplotypes, including a unique NOD haplotype, associated with varying levels of T1D susceptibility. Haplotype diversity within this interval between congenic NOD mouse strains was due to a recombination hotspot that generated four crossover breakpoints, including one with a comp..
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Awarded by National Institute of Diabetes and Digestive and Kidney Diseases
Funding Acknowledgements
We thank S. Foote, J. Stankovich, Y. Hu, and S. Mannering for useful discussions; V. Marshall, M. Martyn, and G. Brammar for technical assistance; E.H. Leiter for providing genomic DNA for various inbred mouse strains; and the mouse care facility staff at the Walter & Eliza Hall Institute and Department of Medicine at The University of Melbourne. This work was supported by the Juvenile Diabetes Research Foundation (1-2005-925), the Cooperative Research Centre for Discovery of Genes for Common Human Diseases, the Australian NHMRC (575552), and the NIH/NIDDK (1R01 DK062882-01A1). I.K.L.T. is supported by a Melbourne International Research Scholarship. N.W. and M.P.A. are supported by Australian Postgraduate Awards. M.P.A. is also supported by a St. Vincent's Institute Foundation Scholarship. C.E. is supported by a Peter Doherty Fellowship. M.B. is supported by an NHMRC Career Development Award. G.S. is supported by a NHMRC Senior Research Fellowship. G.M. is supported by NHMRC Program Grant 516700 and by the Diabetes Research Foundation of Western Australia. T.S. is supported by an Australia Fellowship.