Thomas A, Camp N J, Farnham J M, Allen-Brady K, Cannon-Albright L A
Department of Biomedical Informatics, University of Utah, 391 Chipeta Way, Salt Lake City, UT 84108, USA.
Ann Hum Genet. 2008 Mar;72(Pt 2):279-87. doi: 10.1111/j.1469-1809.2007.00406.x. Epub 2007 Dec 18.
We examine the utility of high density genotype assays for predisposition gene localization using extended pedigrees. Results for the distribution of the number and length of genomic segments shared identical by descent among relatives previously derived in the context of genomic mismatch scanning are reviewed in the context of dense single nucleotide polymorphism maps. We use long runs of loci at which cases share a common allele identically by state to localize hypothesized predisposition genes. The distribution of such runs under the hypothesis of no genetic effect is evaluated by simulation. Methods are illustrated by analysis of an extended prostate cancer pedigree previously reported to show significant linkage to chromosome 1p23. Our analysis establishes that runs of simple single locus statistics can be powerful, tractable and robust for finding DNA shared between relatives, and that extended pedigrees offer powerful designs for gene detection based on these statistics.
我们使用扩展家系研究高密度基因型检测在易感性基因定位中的效用。在密集单核苷酸多态性图谱的背景下，回顾了先前在基因组错配扫描中得出的亲属间通过血缘共享的基因组片段数量和长度的分布结果。我们利用病例通过状态相同地共享一个共同等位基因的长片段基因座来定位假设的易感性基因。通过模拟评估在无遗传效应假设下此类片段的分布。通过对先前报道显示与1p23染色体有显著连锁的一个扩展前列腺癌家系进行分析来说明这些方法。我们的分析表明，简单单基因座统计片段对于寻找亲属间共享的DNA可能是强大、易于处理且稳健的，并且扩展家系基于这些统计数据为基因检测提供了强大的设计。
