title: The F7 gene and clotting factor VII levels: dissection of a human quantitative trait locus.
abstract: 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.
authors.affiliation: Unitat d'Hemostasia i Trombosi, Departament d'Hematologia, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Soria
authors.forename: Laura
authors.initials: L
authors.lastname: Almasy
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Souto
authors.forename: Maria
authors.initials: M
authors.lastname: Sabater-Lleal
authors.forename: Jordi
authors.initials: J
authors.lastname: Fontcuberta
authors.forename: John
authors.initials: J
authors.lastname: Blangero
mesh_terms: D001499:Bayes Theorem; D001777:Blood Coagulation / Q000235:genetics*; D001778:Blood Coagulation Disorders / Q000235:genetics*; D005167:Factor VII / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D008957:Models, Genetic; D011110:Polymorphism, Genetic / Q000235:genetics*; D040641:Quantitative Trait Loci; D019655:Quantitative Trait, Heritable; D020539:Sequence Analysis, Protein
chemical_list: D005167:Factor VII