Soria Jose Manuel, Almasy Laura, Souto Juan Carlos, Sabater-Lleal Maria, Fontcuberta Jordi, Blangero John
Unitat d'Hemostasia i Trombosi, Departament d'Hematologia, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Hum Biol. 2005 Oct;77(5):561-75. doi: 10.1353/hub.2006.0006.
Localization of human quantitative trait loci (QTLs) is now routine. However, identifying their functional DNA variants is still a formidable challenge. We present a complete dissection of a human QTL using novel statistical techniques to infer the most likely functional polymorphisms of a QTL that influence plasma levels of clotting factor VII (FVII), a risk factor for cardiovascular disease. Resequencing of 15 kb in and around the F7 gene identified 49 polymorphisms, which were then genotyped in 398 people. Using a Bayesian quantitative trait nucleotide (BQTN) method, we identified four to seven functional variants that completely account for this QTL. These variants include both rare coding variants and more common, potentially regulatory polymorphisms in intronic and promoter regions.
人类数量性状基因座（QTL）的定位如今已成为常规操作。然而，识别其功能性DNA变异仍然是一项艰巨的挑战。我们利用新颖的统计技术对一个人类QTL进行了全面剖析，以推断影响凝血因子VII（FVII）血浆水平的QTL最可能的功能多态性，FVII是心血管疾病的一个风险因素。对F7基因及其周围15 kb区域进行重测序，鉴定出49个多态性位点，随后在398人中对这些位点进行基因分型。使用贝叶斯数量性状核苷酸（BQTN）方法，我们鉴定出四到七个完全解释该QTL的功能变异。这些变异包括罕见的编码变异以及内含子和启动子区域中更常见的潜在调控多态性。
