MHC区域的多单核苷酸多态性分析：HLA - A1 - B8 - DR3单倍型的显著保守性

Multi-SNP analysis of MHC region: remarkable conservation of HLA-A1-B8-DR3 haplotype.

作者信息

Aly Theresa A, Eller Elise, Ide Akane, Gowan Katherine, Babu Sunanda R, Erlich Henry A, Rewers Marian J, Eisenbarth George S, Fain Pamela R

机构信息

Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Mail Stop B140, P.O. Box 6511, Aurora, CO 80045-6511, USA.

出版信息

Diabetes. 2006 May;55(5):1265-9. doi: 10.2337/db05-1276.

DOI:10.2337/db05-1276

PMID:16644681

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.

摘要

现在已有技术能够经济高效地分析数千个单核苷酸多态性（SNP）。我们最近通过对一小系列I类等位基因和微卫星标记进行基因分型证实，主要组织相容性复合体（MHC）上的扩展单倍型HLA - A1 - B8 - DR3（8.1 AH）是一种常见且保守的单倍型。为了进一步评估DR3单倍型的保守区域，我们用一组跨越MHC区域4.8 Mb的656个SNP对31个8.1 AH和29个其他DR3单倍型进行了基因分型。这种多SNP评估揭示了一个2.9 Mb的区域，对于所有31个8.1 AH来说基本是不变的。在所分析的656个SNP中，31个8.1 AH在384个连续SNP上的一致性>99.9%。未来关于MHC相关的1型糖尿病易感性的关联研究需要考虑8.1 AH的广泛保守性，因为携带这种单倍型的个体无法提供关于该单倍型上存在的等位基因差异效应的信息。