Zeggini Eleftheria, Barton Anne, Eyre Stephen, Ward Daniel, Ollier William, Worthington Jane, John Sally
Centre for Integrated Genomic Medical Research, University of Manchester, Manchester, UK.
BMC Genet. 2005 Apr 25;6:21. doi: 10.1186/1471-2156-6-21.
The selection of markers in association studies can be informed through the use of haplotype blocks. Recent reports have determined the genomic architecture of chromosomal segments through different haplotype block definitions based on linkage disequilibrium (LD) measures or haplotype diversity criteria. The relative applicability of distinct block definitions to association studies, however, remains unclear. We compared different block definitions in 6.1 Mb of chromosome 17q in 189 unrelated healthy individuals. Using 137 single nucleotide polymorphisms (SNPs), at a median spacing of 15.5 kb, we constructed haplotype block maps using published methods and additional methods we have developed. Haplotype tagging SNPs (htSNPs) were identified for each map.
Blocks were found to be shorter and coverage of the region limited with methods based on LD measures, compared to the method based on haplotype diversity. Although the distribution of blocks was highly variable, the number of SNPs that needed to be typed in order to capture the maximum number of haplotypes was consistent.
For the marker spacing used in this study, choice of block definition is not important when used as an initial screen of the region to identify htSNPs. However, choice of block definition has consequences for the downstream interpretation of association study results.
关联研究中标记的选择可通过单倍型块的使用来指导。最近的报告基于连锁不平衡（LD）测量或单倍型多样性标准，通过不同的单倍型块定义确定了染色体片段的基因组结构。然而，不同块定义在关联研究中的相对适用性仍不明确。我们在189名无亲缘关系的健康个体中，对17号染色体长臂6.1 Mb区域的不同块定义进行了比较。利用137个单核苷酸多态性（SNP），中位间距为15.5 kb，我们采用已发表的方法以及我们开发的其他方法构建了单倍型块图谱。为每个图谱鉴定了单倍型标签SNP（htSNP）。
与基于单倍型多样性的方法相比，基于LD测量的方法发现块更短，区域覆盖范围有限。虽然块的分布高度可变，但为捕获最大数量单倍型而需要分型的SNP数量是一致的。
对于本研究中使用的标记间距，当用作识别htSNP的区域的初步筛选时，块定义的选择并不重要。然而，块定义的选择会对关联研究结果的下游解释产生影响。
