Sequence variation and genetic evolution at the human F12 locus: mapping quantitative trait nucleotides that influence FXII plasma levels
9 páginas, 2 figuras, 2 tablas.-- et al.
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2010-02
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dig-ibe-es-10261-436272021-12-28T16:51:32Z Sequence variation and genetic evolution at the human F12 locus: mapping quantitative trait nucleotides that influence FXII plasma levels Calafell, Francesc Ramírez-Soriano, Anna Sikora, Martin Soria, José Manuel 9 páginas, 2 figuras, 2 tablas.-- et al. The level of Factor XII (FXII) is an important phenotype that exhibits a high genetic component and is associated with thrombotic disease. In a genome-wide linkage scan, we demonstrated that the F12 gene represents a quantitative trait locus (QTL) that influences FXII levels. The current study investigated the genetic architecture of the F12 gene to locate polymorphism(s) responsible for the variation of FXII levels. Re-sequencing of the F12 gene in 40 unrelated individuals (selected from the tails of normal distribution of FXII levels) identified 26 polymorphisms which were genotyped in 398 individuals belonging to 21 families from the GAIT Project. By a measured genotype association analysis, eight of 26 SNPs showed significant P-values less than 10−5 (after multiple test correction) with FXII levels. In addition, the Bayesian Quantitative Trait Nucleotide method, which infers those polymorphisms most likely to have a direct influence on the trait under study, provided evidence that only rs1801020 variation accounted for the variance attributed to this QTL. Moreover, we have analyzed the evolutionary processes that produced the variation in F12 gene and concluded that is evolutionarily neutral and that the T allele of the rs1801020 appeared ∼100 000 years ago and spread to most human populations rising to high frequencies by genetic drift. Our study provides a template for future genetic studies of human quantitative traits, as we move beyond QTL localization to the polymorphisms responsible for the variation of important biomedical phenotypes. This work was supported by National Institutes of Health (grants No. 2 R01 HL070751-05); Ministerio de Sanidad y Consumo (PI-08/0420, PI-08/0756); Redes Temáticas de Investigación Cooperativa (RECAVA: Exp-06/0014/ 0016RD) and Ministerio de Ciencia y Tecnología (SAF2008/ 01859). J.M.S. was supported by ‘Programa d’Estabilització d’Investigadors de la Direcció d’Estrategia i Coordinació del Departament de Salut’ (Generalitat de Catalunya). Peer reviewed 2011-12-22T09:21:48Z 2011-12-22T09:21:48Z 2010-02 artículo http://purl.org/coar/resource_type/c_6501 Human Molecular Genetics 19(3): 517-525 (2010) 0964-6906 http://hdl.handle.net/10261/43627 10.1093/hmg/ddp517 1460-2083 19933701 en http://dx.doi.org/10.1093/hmg/ddp517 none Oxford University Press |
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9 páginas, 2 figuras, 2 tablas.-- et al. |
| format |
artículo |
| author |
Calafell, Francesc Ramírez-Soriano, Anna Sikora, Martin Soria, José Manuel |
| spellingShingle |
Calafell, Francesc Ramírez-Soriano, Anna Sikora, Martin Soria, José Manuel Sequence variation and genetic evolution at the human F12 locus: mapping quantitative trait nucleotides that influence FXII plasma levels |
| author_facet |
Calafell, Francesc Ramírez-Soriano, Anna Sikora, Martin Soria, José Manuel |
| author_sort |
Calafell, Francesc |
| title |
Sequence variation and genetic evolution at the human F12 locus: mapping quantitative trait nucleotides that influence FXII plasma levels |
| title_short |
Sequence variation and genetic evolution at the human F12 locus: mapping quantitative trait nucleotides that influence FXII plasma levels |
| title_full |
Sequence variation and genetic evolution at the human F12 locus: mapping quantitative trait nucleotides that influence FXII plasma levels |
| title_fullStr |
Sequence variation and genetic evolution at the human F12 locus: mapping quantitative trait nucleotides that influence FXII plasma levels |
| title_full_unstemmed |
Sequence variation and genetic evolution at the human F12 locus: mapping quantitative trait nucleotides that influence FXII plasma levels |
| title_sort |
sequence variation and genetic evolution at the human f12 locus: mapping quantitative trait nucleotides that influence fxii plasma levels |
| publisher |
Oxford University Press |
| publishDate |
2010-02 |
| url |
http://hdl.handle.net/10261/43627 |
| work_keys_str_mv |
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1777668533823471616 |