Multi-SNP Analysis of MHC Region
Remarkable Conservation of HLA-A1-B8-DR3 Haplotype
- Theresa A. Aly1,
- Elise Eller1,
- Akane Ide1,
- Katherine Gowan2,
- Sunanda R. Babu1,
- Henry A. Erlich3,
- Marian J. Rewers4,
- George S. Eisenbarth1 and
- Pamela R. Fain12
- 1Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Aurora, Colorado
- 2Human Medical Genetics Program Aurora, Colorado
- 3Roche Molecular Systems, Berkeley, California
- 4Department of Preventive Medicine and Biometrics, University of Colorado at Denver and Health Sciences Center, Denver, Colorado
- Address correspondence and reprint requests to Pamela R. Fain PhD, Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Mail Stop B140, P.O. Box 6511, Aurora, CO 80045-6511. E-mail: pam.fain{at}UCHSC.edu
Abstract
Technology has become available to cost-effectively analyze thousands of single nucleotide polymorphisms (SNPs). We recently confirmed by genotyping a small series of class I alleles and microsatellite markers that the extended haplotype HLA-A1-B8-DR3 (8.1 AH) at the major histocompatibility complex (MHC) is a common and conserved haplotype. To further evaluate the region of conservation of the DR3 haplotypes, we genotyped 31 8.1 AHs and 29 other DR3 haplotypes with a panel of 656 SNPs spanning 4.8 Mb in the MHC region. This multi-SNP evaluation revealed a 2.9-Mb region that was essentially invariable for all 31 8.1 AHs. The 31 8.1 AHs were >99.9% identical for 384 consecutive SNPs of the 656 SNPs analyzed. Future association studies of MHC-linked susceptibility to type 1 diabetes will need to account for the extensive conservation of the 8.1 AH, since individuals who carry this haplotype provide no information about the differential effects of the alleles that are present on this haplotype.
- 8.1 AH, HLA-A1-B8-DR3
- DAISY, Diabetes Autoimmunity Study of the Young
- LD, linkage disequilibrium
- MHC, major histocompatibility complex
- SNP, single nucleotide polymorphism
- STR, short tandem repeat
Footnotes
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Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted January 23, 2006.
- Received September 29, 2005.
- DIABETES
