Stenzel Annette, Lu Timothy, Koch W Andreas, Hampe Jochen, Guenther Simone M, De La Vega Francisco M, Krawczak Michael, Schreiber Stefan
Abteilung für Allgemeine Innere Medizin, Universitätsklinikum Schleswig-Holstein, Christian-Albrechts-Universität Kiel, 24105 Kiel, Germany.
Hum Genet. 2004 Mar;114(4):377-85. doi: 10.1007/s00439-003-1075-5. Epub 2004 Jan 22.
Single nucleotide polymorphisms (SNPs) in the human genome are thought to be organised into blocks of high internal linkage disequilibrium (LD), separated by intermittent recombination hotspots. Since understanding haplotype structure is critical for an accurate assessment of inter-individual genetic differences, we investigated up to 968 SNPs from a 10-Mb region on chromosome 6p21, including the human major histocompatibility complex (MHC), in five different population samples (45-550 individuals). Regions of well-defined block structure were found to coexist alongside large areas lacking any clear structure; occasional long-range LD was observed in all five samples. The four white populations analysed were remarkably similar in terms of the extend and spatial distribution of local LD. In US African Americans, the distribution of LD was similar to that in the white populations but the observed haplotype diversity was higher. The existence of large regions without any clear block structure renders the systematic and thorough construction of SNP haplotype maps a crucial prerequisite for disease-association studies.
人类基因组中的单核苷酸多态性（SNP）被认为是组织成具有高度内部连锁不平衡（LD）的区域，这些区域由间歇性的重组热点分隔开。由于了解单倍型结构对于准确评估个体间的遗传差异至关重要，我们在五个不同的人群样本（45 - 550人）中研究了位于6号染色体p21区域10 Mb范围内的多达968个SNP，该区域包括人类主要组织相容性复合体（MHC）。发现明确的区域结构块与缺乏任何清晰结构的大片区域共存；在所有五个样本中都观察到了偶尔的长程LD。所分析的四个白人种群在局部LD的范围和空间分布方面非常相似。在美国非裔美国人中，LD的分布与白人种群相似，但观察到的单倍型多样性更高。存在大片没有任何清晰区域结构的区域使得系统而全面地构建SNP单倍型图谱成为疾病关联研究的关键前提。
