4.7 Article

Defining multiple common completely conserved major histocompatibility complex SNP haplotypes

Journal

CLINICAL IMMUNOLOGY
Volume 132, Issue 2, Pages 203-214

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2009.03.530

Keywords

Type 1 diabetes; MHC; HLA; Extended haplotypes; SNP; 8.1; DR8

Categories

Funding

  1. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  2. National Institute of Allergy and Infectious Diseases (NIAID)
  3. National Human Genome Research Institute (NHGRI)
  4. National Institute of Child Health and Human Development (NICHD)
  5. Juvenile Diabetes Research Foundation International (JDRF)
  6. National Institutes of Health [DK32083, DK057538]
  7. Diabetes Autoimmunity Study in the Young [DK32493]
  8. Autoimmunity Prevention Center [AI050864]
  9. Diabetes Endocrine Research Center [P30 DK57516]
  10. Clinical Research Centers [MO1 RR00069, MO1 RR00051]
  11. Immune Tolerance Network [AI15416]
  12. American Diabetes Association
  13. Juvenile Diabetes Research Foundation
  14. Children's Diabetes Foundation
  15. Brehm Coalition
  16. [U01 DK062418]

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The availability of both HLA data and genotypes for thousands of SNPs across the major histocompatibility complex (MHC) in 1240 complete families of the Type 1 Diabetes Genetics Consortium allowed us to analyze the occurrence and extent of megabase contiguous identity for founder chromosomes from unrelated individuals. We identified 82 HLA-defined haplotype groups, and within these groups, megabase regions of SNIP identity were readily apparent. The conserved chromosomes within the 82 haplotype groups comprise approximately one third of the founder chromosomes. It is currently unknown whether such frequent conservation for groups of unrelated individuals is specific to the MHC, or if initial binning by highly polymorphic HLA alleles facilitated detection of a more general phenomenon within the MHC. Such common identity, specifically across the MHC, impacts type 1 diabetes susceptibility and may impact transplantation between unrelated individuals. (C) 2009 Elsevier Inc. All rights reserved.

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