English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/115527
Compartir / Impacto:
Estadísticas
Add this article to your Mendeley library MendeleyBASE
Citado 2 veces en Web of Knowledge®  |  Pub MebCentral Ver citas en PubMed Central  |  Ver citas en Google académico
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar otros formatos: Exportar EndNote (RIS)Exportar EndNote (RIS)Exportar EndNote (RIS)
Título

Positive Selection in the Chromosome 16 VKORC1 Genomic Region Has Contributed to the Variability of Anticoagulant Response in Humans

Autor Patillon, Blandine; Luisi, Pierre ; Blanché, Hélène; Patin. Etienne; Cann, Howard N.; Genin, Emmanuelle; Sabbagh, Audrey
Fecha de publicación 28-dic-2012
EditorPublic Library of Science
Citación PLoS ONE 7(12): e53049 (2012)
ResumenVKORC1 (vitamin K epoxide reductase complex subunit 1, 16p11.2) is the main genetic determinant of human response to oral anticoagulants of antivitamin K type (AVK). This gene was recently suggested to be a putative target of positive selection in East Asian populations. In this study, we genotyped the HGDP-CEPH Panel for six VKORC1 SNPs and downloaded chromosome 16 genotypes from the HGDP-CEPH database in order to characterize the geographic distribution of footprints of positive selection within and around this locus. A unique VKORC1 haplotype carrying the promoter mutation associated with AVK sensitivity showed especially high frequencies in all the 17 HGDP-CEPH East Asian population samples. VKORC1 and 24 neighboring genes were found to lie in a 505 kb region of strong linkage disequilibrium in these populations. Patterns of allele frequency differentiation and haplotype structure suggest that this genomic region has been submitted to a near complete selective sweep in all East Asian populations and only in this geographic area. The most extreme scores of the different selection tests are found within a smaller 45 kb region that contains VKORC1 and three other genes (BCKDK, MYST1 (KAT8), and PRSS8) with different functions. Because of the strong linkage disequilibrium, it is not possible to determine if VKORC1 or one of the three other genes is the target of this strong positive selection that could explain present-day differences among human populations in AVK dose requirement. Our results show that the extended region surrounding a presumable single target of positive selection should be analyzed for genetic variation in a wide range of genetically diverse populations in order to account for other neighboring and confounding selective events and the hitchhiking effect. © 2012 Patillon et al.
Versión del editorhttp://dx.doi.org/10.1371/journal.pone.0053049
URI http://hdl.handle.net/10261/115527
DOI10.1371/journal.pone.0053049
Identificadoresdoi: 10.1371/journal.pone.0053049
issn: 1932-6203
Aparece en las colecciones: (IBE) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
chromosome_16VKORC1_Patillon.pdf937,45 kBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo
 



NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.