Design and evaluation of a panel os single-nucleotide polymorphisms in microRNA genomic regions for association studies in human disease

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• dc.contributor.author Muiños Gimeno, Margaritaca
• dc.contributor.author Montfort, Magdaca
• dc.contributor.author Bayés, Mònicaca
• dc.contributor.author Estivill, Xavier, 1955-ca
• dc.contributor.author Espinosa Parrilla, Yolanda, 1971-ca
• dc.date.accessioned 2012-03-13T12:28:54Z
• dc.date.available 2012-03-13T12:28:54Z
• dc.date.issued 2010ca
• dc.description.abstract MicroRNAs (miRNA) are recognized posttranscriptional gene repressors involved in the control of almost every biological process. Allelic variants in these regions may be an important source of phenotypic diversity and contribute to disease susceptibility. We analyzed the genomic organization of 325 human miRNAs (release 7.1, miRBase) to construct a panel of 768 single-nucleotide polymorphisms (SNPs) covering approximately 1 Mb of genomic DNA, including 131 isolated miRNAs (40%) and 194 miRNAs arranged in 48 miRNA clusters, as well as their 5-kb flanking regions. Of these miRNAs, 37% were inside known protein-coding genes, which were significantly associated with biological functions regarding neurological, psychological or nutritional disorders. SNP coverage analysis revealed a lower SNP density in miRNAs compared with the average of the genome, with only 24 SNPs located in the 325 miRNAs studied. Further genotyping of 340 unrelated Spanish individuals showed that more than half of the SNPs in miRNAs were either rare or monomorphic, in agreement with the reported selective constraint on human miRNAs. A comparison of the minor allele frequencies between Spanish and HapMap population samples confirmed the applicability of this SNP panel to the study of complex disorders among the Spanish population, and revealed two miRNA regions, hsa-mir-26a-2 in the CTDSP2 gene and hsa-mir-128-1 in the R3HDM1 gene, showing geographical allelic frequency variation among the four HapMap populations, probably because of differences in natural selection. The designed miRNA SNP panel could help to identify still hidden links between miRNAs and human disease.
• dc.description.sponsorship This work was supported by the 'Instituto Carlos III and Fondo de Investigaciones Sanitarias' [CIBER-CB06/02/0058, CIBER-SAM, FIS/ISCIII:P1052565, ISCIII:GO3/184], the 'Fundació la Marató-TV3' [014331], the 'Departament d’Universitats Innovació i Empresa, Generalitat de Catalunya' [2005SGR00008] and the European Union Sixth Framework Programme Integrated Project SIROCCO [Grant LSHG-CT-2006-037900]
• dc.format.mimetype application/pdfca
• dc.identifier.citation Muiños-Gimeno M, Montfort M, Bayés M, Estivill X, Espinosa-Parrilla Y. Design and evaluation of a panel os single-nucleotide polymorphisms in microRNA genomic regions for association studies in human disease. European Journal of Human Genetics. 2010;18(2):218-26. DOI: 10.1038/ejhg.2009.165ca
• dc.identifier.doi http://dx.doi.org/10.1038/ejhg.2009.165
• dc.identifier.issn 1018-4813ca
• dc.identifier.uri http://hdl.handle.net/10230/16289
• dc.language.iso engca
• dc.publisher Nature Publishing Groupca
• dc.relation.ispartof European Journal of Human Genetics. 2010;18(2):218-26
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP6/037900
• dc.rights © 2010 Macmillan Publishers Limited All rights reservedca
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.keyword miRNA
• dc.subject.keyword Single nucleotide polymorphism
• dc.subject.keyword HapMap
• dc.subject.keyword Population genetics
• dc.subject.other Genètica humana -- Variació
• dc.subject.other Interaccions ARN-proteïnes
• dc.title Design and evaluation of a panel os single-nucleotide polymorphisms in microRNA genomic regions for association studies in human diseaseca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/acceptedVersion