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Diabetes 54:1879-1883, 2005
© 2005 by the American Diabetes Association, Inc.

Brief Genetics Reports

"Extended" A1, B8, DR3 Haplotype Shows Remarkable Linkage Disequilibrium but Is Similar to Nonextended Haplotypes in Terms of Diabetes Risk

Akane Ide, Sunanda R. Babu, David T. Robles, Tianbao Wang, Henry A. Erlich, Teodorica L. Bugawan, Marian Rewers, Pamela R. Fain, and George S. Eisenbarth

Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver, Colorado

To evaluate potential differential diabetes risk of DR3 haplotypes we have evaluated class I alleles as well as two microsatellites previously associated with differential risk associated with DR3 haplotypes. We found that over one-third of patient DR3 chromosomes consisted of an extended DR3 haplotype, from DQ2 to D6S2223 (DQ2, DR3, D6S273-143, MIC-A5.1, HLA-B8, HLA-Cw7, HLA-A1, and D6S2223-177) with an identical extended haplotype in controls. The extended haplotype was present more frequently (35.1% of autoimmune-associated DR3 haplotypes, 39.4% of control DR3 haplotypes) than other haplotypes (no other haplotype >5% of DR3 haplotypes) and remarkably conserved, but it was not transmitted from parents to affected children more frequently than nonconserved DR3-bearing haplotypes. This suggests that if all alleles are truly identical for the major A1, B8, DR3 haplotype (between A1 and DR3), with different alleles on nonconserved haplotypes without differential diabetes risk, then in this region of the genome DR3-DQ2 may be the primary polymorphisms of common haplotypes contributing to diabetes risk.

Address correspondence and reprint requests to George S. Eisenbarth MD, PhD, Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, 4200 East 9th Ave., Box B140, Denver, CO 80262. E-mail: george.eisenbarth{at}uchsc.edu

Abbreviations: DAISY, Diabetes Autoimmunity Study in the Young of Denver, Colorado; MHC, major histocompatibility complex


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T. A. Aly, E. Eller, A. Ide, K. Gowan, S. R. Babu, H. A. Erlich, M. J. Rewers, G. S. Eisenbarth, and P. R. Fain
Multi-SNP Analysis of MHC Region: Remarkable Conservation of HLA-A1-B8-DR3 Haplotype.
Diabetes, May 1, 2006; 55(5): 1265 - 1269.
[Abstract] [Full Text] [PDF]


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