The role of large pedigrees in an era of high-throughput sequencing.
The role of large pedigrees in an era of high-throughput sequencing.
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DOI：
10.1007/s00439-012-1190-2
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发表时间：
2012-10
期刊：
影响因子：
5.3
通讯作者：
Wijsman EM
中科院分区：
文献类型：
--
作者：
Wijsman EM
罕见的变异是目前人类遗传学的前沿。大的系谱设计实用、高效，非常适合研究罕见的变异。在大型家系中，与一种性状共分离的特定稀有变异将出现足够多的数量，以便通过充分利用家系信息的方法来测量影响和评估关联证据。最近的研究表明，来自连锁分析的证据可以集中调查，既减少了多重测试负担，又扩大了可以评估和跟踪的变种。大的系谱设计只需要在基于总体的设计中识别感兴趣的稀有变异所需的样本量的一小部分，而且许多高度合适、易于理解和可用的统计和计算工具已经存在。由现有丰富的表型和基因组扫描数据的大型家系组成的样本应该是在搜索复杂性状的决定因素时进行高通量测序的主要候选对象。
Rare variation is the current frontier in human genetics. The large pedigree design is practical, efficient, and well-suited for investigating rare variation. In large pedigrees, specific rare variants that co-segregate with a trait will occur in sufficient numbers so that effects can be measured, and evidence for association can be evaluated, by making use of methods that fully use the pedigree information. Evidence from linkage analysis can focus investigation, both reducing the multiple testing burden and expanding the variants that can be evaluated and followed up, as recent studies have shown. The large pedigree design requires only a small fraction of the sample size needed to identify rare variants of interest in population-based designs, and many highly suitable, well-understood, and available statistical and computational tools already exist. Samples consisting of large pedigrees with existing rich phenotype and genome scan data should be prime candidates for high-throughput sequencing in the search of the determinants of complex traits.
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