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A region of linkage to type 1 diabetes has been defined on human chromosome 10p11-q11 (IDDM10; P = 0.0007) using 236 UK and 76 US affected sibpairs and a 1 cM resolution microsatellite marker map. Analysis by the transmission disequilibrium test (TDT) in 1159 families with at least one diabetic child, from the UK, the US, Norway, Sardinia and Italy provided additional support for linkage at D10S193 (P = 0.006, Pc = 0.17). Notably, 5.1 cM distal to D10S193, marker D10S588 also provided positive TDT results (P = 0.009, Pc = 0.25) but the allele under analysis was also preferentially transmitted to nonaffected siblings (P = 0.0008, Pc = 0.02). This allele was positively associated in an independent UK case control study and, importantly, was neutrally transmitted in control CEPH families. These results suggest a type 1 diabetes susceptibility locus on chromosome 10p11-q11 (provisionally designated IDDM10) and demonstrate the necessity of analysis of non affected siblings in disease families, as well as analysis of control families.

Original publication

DOI

10.1093/hmg/6.7.1011

Type

Journal article

Journal

Human molecular genetics

Publication Date

07/1997

Volume

6

Pages

1011 - 1016

Addresses

The Wellcome Trust Centre for Human Genetics, Nuffield Department of Surgery, University of Oxford, UK.

Keywords

Chromosomes, Human, Pair 10, Humans, Diabetes Mellitus, Type 1, Genetic Predisposition to Disease, Genetic Markers, Chromosome Mapping, Microsatellite Repeats, Adolescent, European Continental Ancestry Group, United States, Italy, Norway, Genetic Linkage, United Kingdom