Nature Genetics
19, 292 - 296 (1998)
doi:10.1038/985
A second-generation screen of the human genome for susceptibility to
insulin-dependent diabetes mellitusPatrick Concannon, Kathryn J. Gogolin-Ewens2, David A. Hinds3, Beth Wapelhorst1, V. Annem Morrison1, Brigid Stirling1, Mirna Mitra4, Jennifer Farmer2, Sloan R. Williams2, Nancy J. Cox5, Graeme I. Bell4, Neil Risch3
& Richard S. Spielman1
Virginia Mason Research Center, 1000
Seneca St., Seattle, Washington 98101,
USA and Department of Immunology, UW School of Medicine,
Seattle, Washington 98195, USA
2
Department of Genetics, University of Pennsylvania
School of Medicine, 415 Curie Blvd, Philadelphia,
Pennsylvania 19104-6145, USA. 3
Department of Genetics, Stanford University,
Stanford, California 94305-5120, USA. 4
Howard Hughes Medical Institute and Departments of
Biochemistry and Molecular Biology, and Medicine, University of Chicago,
5841 South Maryland Avenue, MC1028, Chicago,
Illinois, 60637 USA. 5
Department of Medicine, University of Chicago,
5841 South Maryland Avenue, MC1028, Chicago,
Illinois 60637, USA.
Correspondence should be addressed to Patrick Concannon patcon@u.washington.edu or Richard S. Spielman spielman@pobox.upenn.eduDuring the past decade, the genetics of type 1 (insulin-dependent)
diabetes mellitus (IDDM) has been studied extensively and the disorder has
become a paradigm for genetically complex diseases. Previous genome screens1,
2 and studies focused on candidate genes3,
4,
5,
6,
7,
8,
9
have provided evidence for genetic linkage between polymorphic DNA markers
and 15 putative IDDM susceptibility loci, designated IDDM1-IDDM15
. We have carried out a second-generation screen of the genome for linkage
and analysed the data by multipoint linkage methods. An initial panel of 212
affected sibpairs (ASPs) was genotyped for 438 markers spanning all autosomes,
and an additional 467 ASPs were used for follow-up genotyping. Other than
the well-established linkage with the HLA region at chromosome 6p21.3, there
was only one region, located on chromosome 1q and not previously reported,
where the log likelihood ratio (lod) was greater than 3. Lods between 1.0
and 1.8 were found in six other regions, three of which have been reported
in other studies. Another reported region10, on chromosome 6q
and loosely linked to HLA, also had an elevated lod. Little or no support
was found for most reported IDDM loci (lods were less than 1), despite larger
sample sizes in the present study.
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