Almasy Laura, Blangero John
Department of Genetics, Southwest Foundation for Biomedical Research, P.O. Box 760549, San Antonio, TX 78245-0549, USA.
Genetica. 2009 Jun;136(2):333-40. doi: 10.1007/s10709-008-9305-3. Epub 2008 Jul 31.
Human quantitative trait locus (QTL) linkage mapping, although based on classical statistical genetic methods that have been around for many years, has been employed for genome-wide screening for only the last 10-15 years. In this time, there have been many success stories, ranging from QTLs that have been replicated in independent studies to those for which one or more genes underlying the linkage peak have been identified to a few with specific functional variants that have been confirmed in in vitro laboratory assays. Despite these successes, there is a general perception that linkage approaches do not work for complex traits, possibly because many human QTL linkage studies have been limited in sample size and have not employed the family configurations that maximize the power to detect linkage. We predict that human QTL linkage studies will continue to be productive for the next several years, particularly in combination with RNA expression level traits that are showing evidence of regulatory QTLs of large effect sizes and in combination with high-density genome-wide SNP panels. These SNP panels are being used to identify QTLs previously localized by linkage and linkage results are being used to place informative priors on genome-wide association studies.
人类数量性状基因座（QTL）连锁图谱绘制，尽管基于已存在多年的经典统计遗传学方法，但仅在过去10至15年才被用于全基因组筛选。在此期间，有许多成功案例，从在独立研究中被复制的QTL，到那些已确定连锁峰下一个或多个基因的案例，再到少数在体外实验室检测中已得到证实的具有特定功能变异的案例。尽管取得了这些成功，但人们普遍认为连锁方法不适用于复杂性状，这可能是因为许多人类QTL连锁研究的样本量有限，且未采用能最大限度提高连锁检测能力的家系结构。我们预测，未来几年人类QTL连锁研究仍将富有成效，特别是与显示出具有大效应量调控QTL证据的RNA表达水平性状相结合，以及与高密度全基因组SNP面板相结合。这些SNP面板正被用于识别先前通过连锁定位的QTL，而连锁结果正被用于在全基因组关联研究中设置信息性先验。
