Romero Viviana, Larsen Charles E, Duke-Cohan Jonathan S, Fox Edward A, Romero Tatiana, Clavijo Olga P, Fici Dolores A, Husain Zaheed, Almeciga Ingrid, Alford Dennis R, Awdeh Zuheir L, Zuñiga Joaquin, El-Dahdah Lama, Alper Chester A, Yunis Edmond J
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA, USA.
BMC Genet. 2007 Apr 12;8:14. doi: 10.1186/1471-2156-8-14.
The definition of human MHC class I haplotypes through association of HLA-A, HLA-Cw and HLA-B has been used to analyze ethnicity, population migrations and disease association.
Here, we present HLA-E allele haplotype association and population linkage disequilibrium (LD) analysis within the ~1.3 Mb bounded by HLA-B/Cw and HLA-A to increase the resolution of identified class I haplotypes. Through local breakdown of LD, we inferred ancestral recombination points both upstream and downstream of HLA-E contributing to alternative block structures within previously identified haplotypes. Through single nucleotide polymorphism (SNP) analysis of the MHC region, we also confirmed the essential genetic fixity, previously inferred by MHC allele analysis, of three conserved extended haplotypes (CEHs), and we demonstrated that commercially-available SNP analysis can be used in the MHC to help define CEHs and CEH fragments.
We conclude that to generate high-resolution maps for relating MHC haplotypes to disease susceptibility, both SNP and MHC allele analysis must be conducted as complementary techniques.
通过HLA - A、HLA - Cw和HLA - B的关联来定义人类MHC I类单倍型，已被用于分析种族、人口迁移和疾病关联。
在此，我们展示了HLA - E等位基因单倍型关联以及在由HLA - B/Cw和HLA - A界定的约1.3 Mb范围内的群体连锁不平衡（LD）分析，以提高已识别的I类单倍型的分辨率。通过LD的局部解析，我们推断出HLA - E上下游的祖先重组点，这些重组点导致了先前识别的单倍型内的替代块结构。通过对MHC区域的单核苷酸多态性（SNP）分析，我们还证实了先前通过MHC等位基因分析推断出的三种保守扩展单倍型（CEH）的基本遗传稳定性，并且我们证明了商业上可用的SNP分析可用于MHC中以帮助定义CEH和CEH片段。
我们得出结论，为了生成用于将MHC单倍型与疾病易感性相关联的高分辨率图谱，SNP分析和MHC等位基因分析都必须作为互补技术进行。
