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Multipoint linkage analysis of the short arm of chromosome 11 in non-insulin dependent diabetes including maturity onset diabetes of youth
Authors:S. O'Rahilly  P. Patel  O. J. Lehmann  A. Tybjaerg-Hansen  J. Nerup  R. C. Turner  J. S. Wainscoat
Affiliation:(1) Diabetes Research Laboratories, Radcliffe Infirmary, OX2 6HE Oxford, UK;(2) Hagedorn Research Laboratory, Gentofte, Denmark;(3) Department of Haematology, John Radcliffe Hospital, OX3 9DG Oxford, UK
Abstract:Summary Members of three families with maturity onset diabetes of youth (MODY) and seven with ldquocommonrdquo type 2 diabetes were typed for six DNA markers (H-RAS, INS, HBBC, PTH, CALC1, CAT) on the short arm of chromosome 11. Using conventional pairwise linkage analysis, close linkage in the MODY families was excluded for all six markers. By multipoint analysis and a genetic map of the short arm of chromosome 11, MODY was excluded from a region of at least 35 and up to 60 centiMorgans (cM) on the short arm of chromosome 11. Multipoint analysis in the type 2 families also excludes linkage to the INS, H-RAS region of at least 3 and up to 30 cM. This study using multipoint linkage analysis in non-insulin dependent diabetes provides strong evidence against a role for mutations in or around the insulin gene in the causation of MODY or type 2 diabetes in the families studied.
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