Experimentally-derived haplotypes substantially increase the efficiency of linkage disequilibrium studies
Experimentally-derived haplotypes substantially increase the efficiency of linkage disequilibrium studies
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DOI：
10.1038/ng582
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发表时间：
2001-08-01
期刊：
影响因子：
30.8
通讯作者：
Gruber, SB
中科院分区：
文献类型：
--
作者：
Douglas, JA;Boehnke, M;Gruber, SB
人类复杂遗传特征的研究受到确定足够样本量的人群以检测疾病的细微遗传贡献的费用和困难的限制。在这里，我们介绍了一种称为转换（1-4）的体细胞杂交构建策略的应用，该策略最大限度地提高了每个样本个体的基因型信息。该方法允许直接观察个体单倍型，从而消除了从家庭成员收集DNA并进行基因分型以用于基于单倍型的分析的需要。我们描述了验证转换作为全基因组单体型分型的使用的实验数据[并评估了在单体型频率估计的背景下使用转换衍生的单体型而不是常规基因型的理论效率。我们表明，特别是当表型分型是昂贵的，转换为基础的单体型可以更有效和成本效益比标准的基因分型。
The study of complex genetic traits in humans is limited by the expense and difficulty of ascertaining populations of sufficient sample size to detect subtle genetic contributions to disease. Here we introduce an application of a somatic cell hybrid construction strategy called conversion(1-4) that maximizes the genotypic information from each sampled individual. The approach permits direct observation of individual haplotypes, thereby eliminating the need for collecting and genotyping DNA from family members for haplotype-based analyses. We describe experimental data that validate the use of conversion as a whole-genome haplotyping too[ and evaluate the theoretical efficiency of using conversion-derived haplotypes instead of conventional genotypes in the context of haplotype-frequency estimation. We show that, particularly when phenotyping is expensive, conversion-based haplotyping can be more efficient and cost-effective than standard genotyping.