Department of Biostatistics, City of Hope National Medical Center, 1500 E. Duarte Road, Duarte, California 91010, USA.
BMC Genet. 2005 Dec 30;6 Suppl 1(Suppl 1):S79. doi: 10.1186/1471-2156-6-S1-S79.
Haplotype data contain signatures of ancestral alleles and increased information for mapping genes associated with complex traits. The motivation of this paper is to test the feasibility of a recently developed haplotype reconstruction algorithm and to perform haplotype-sharing correlation (HSC) analysis in nuclear families using data provided by the Genetic Analysis Workshop 14 and the Collaborative Study of the Genetics of Alcoholism. As an exemplary analysis, haplotype data on chromosomes 1-6 were reconstructed from genotype data in 93 nuclear families by minimizing both the recombinants in within-family haplotypes and the tree distance in between-family haplotypes. HSC analysis was performed using the best set of reconstructed haplotypes, and chromosome-wide significance was evaluated using a permutation procedure. Three markers were found to have significant haplotype associations with DSM-IV alcohol dependence that exceeded the 0.05 level of chromosome-wide significance: marker rs895941 at 36.7 cM on chromosome 3 (p = 0.03), marker rs1631833 at 109.1 cM on chromosome 4 (p = 0.008), and marker rs953887 at 74.2 cM on chromosome 6 (p = 0.02). These results indicated the usefulness of HSC analysis and provided further evidence on chromosome regions associated with alcohol dependence.
单体型数据包含祖先等位基因的特征，并为与复杂性状相关的基因映射提供了更多信息。本文的目的是测试最近开发的单体型重建算法的可行性，并使用 14 届遗传分析工作坊和酒精中毒遗传学合作研究提供的数据在核家庭中进行单体型共享相关性 (HSC) 分析。作为一个示范分析，通过最小化家庭内单体型中的重组和家庭间单体型中的树距离，从 93 个核家庭的基因型数据中重建了 1-6 号染色体上的单体型数据。使用最佳重建单体型进行 HSC 分析，并使用置换程序评估全染色体的显著性。发现三个标记与 DSM-IV 酒精依赖有显著的单体型关联，超过了全染色体显著性的 0.05 水平：3 号染色体上 36.7cM 的标记 rs895941（p=0.03），4 号染色体上 109.1cM 的标记 rs1631833（p=0.008）和 6 号染色体上 74.2cM 的标记 rs953887（p=0.02）。这些结果表明 HSC 分析的有用性，并提供了与酒精依赖相关的染色体区域的进一步证据。
