| http://purl.uniprot.org/citations/23990973 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23990973 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23990973 | http://www.w3.org/2000/01/rdf-schema#comment | "Psoriasis is an immune-mediated skin disorder that is inherited as a complex genetic trait. Although genome-wide association scans (GWAS) have identified 36 disease susceptibility regions, more than 50% of the genetic variance can be attributed to a single Major Histocompatibility Complex (MHC) locus, known as PSORS1. Genetic studies indicate that HLA-C is the strongest PSORS1 candidate gene, since markers tagging HLA-Cw*0602 consistently generate the most significant association signals in GWAS. However, it is unclear whether HLA-Cw*0602 is itself the causal PSORS1 allele, especially as the role of SNPs that may affect its expression has not been investigated. Here, we have undertaken an in-depth molecular characterization of the PSORS1 interval, with a view to identifying regulatory variants that may contribute to disease susceptibility. By analysing high-density SNP data, we refined PSORS1 to a 179 kb region encompassing HLA-C and the neighbouring HCG27 pseudogene. We compared multiple MHC sequences spanning this refined locus and identified 144 candidate susceptibility variants, which are unique to chromosomes bearing HLA-Cw*0602. In parallel, we investigated the epigenetic profile of the critical PSORS1 interval and uncovered three enhancer elements likely to be active in T lymphocytes. Finally we showed that nine candidate susceptibility SNPs map within a HLA-C enhancer and that three of these variants co-localise with binding sites for immune-related transcription factors. These data indicate that SNPs affecting HLA-Cw*0602 expression are likely to contribute to psoriasis susceptibility and highlight the importance of integrating multiple experimental approaches in the investigation of complex genomic regions such as the MHC."xsd:string |
| http://purl.uniprot.org/citations/23990973 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0071690"xsd:string |
| http://purl.uniprot.org/citations/23990973 | http://purl.uniprot.org/core/author | "Simpson M.A."xsd:string |
| http://purl.uniprot.org/citations/23990973 | http://purl.uniprot.org/core/author | "Simpson M.A."xsd:string |
| http://purl.uniprot.org/citations/23990973 | http://purl.uniprot.org/core/author | "Trembath R.C."xsd:string |
| http://purl.uniprot.org/citations/23990973 | http://purl.uniprot.org/core/author | "Trembath R.C."xsd:string |
| http://purl.uniprot.org/citations/23990973 | http://purl.uniprot.org/core/author | "Barker J.N."xsd:string |
| http://purl.uniprot.org/citations/23990973 | http://purl.uniprot.org/core/author | "Barker J.N."xsd:string |
| http://purl.uniprot.org/citations/23990973 | http://purl.uniprot.org/core/author | "Capon F."xsd:string |
| http://purl.uniprot.org/citations/23990973 | http://purl.uniprot.org/core/author | "Capon F."xsd:string |
| http://purl.uniprot.org/citations/23990973 | http://purl.uniprot.org/core/author | "Spain S.L."xsd:string |
| http://purl.uniprot.org/citations/23990973 | http://purl.uniprot.org/core/author | "Spain S.L."xsd:string |
| http://purl.uniprot.org/citations/23990973 | http://purl.uniprot.org/core/author | "Pullabhatla V."xsd:string |
| http://purl.uniprot.org/citations/23990973 | http://purl.uniprot.org/core/author | "Pullabhatla V."xsd:string |
| http://purl.uniprot.org/citations/23990973 | http://purl.uniprot.org/core/author | "Hayday A.C."xsd:string |
| http://purl.uniprot.org/citations/23990973 | http://purl.uniprot.org/core/author | "Hayday A.C."xsd:string |
| http://purl.uniprot.org/citations/23990973 | http://purl.uniprot.org/core/author | "Tonda R."xsd:string |
| http://purl.uniprot.org/citations/23990973 | http://purl.uniprot.org/core/author | "Tonda R."xsd:string |
| http://purl.uniprot.org/citations/23990973 | http://purl.uniprot.org/core/author | "De Jong P."xsd:string |
| http://purl.uniprot.org/citations/23990973 | http://purl.uniprot.org/core/author | "De Jong P."xsd:string |
| http://purl.uniprot.org/citations/23990973 | http://purl.uniprot.org/core/author | "Clop A."xsd:string |
| http://purl.uniprot.org/citations/23990973 | http://purl.uniprot.org/core/author | "Clop A."xsd:string |
| http://purl.uniprot.org/citations/23990973 | http://purl.uniprot.org/core/author | "Bertoni A."xsd:string |