title: Haplotype sharing analysis identifies a retroviral dUTPase as candidate susceptibility gene for psoriasis.
abstract: The psoriasis susceptibility locus 1 (PSORS1) mutation is assumed to reside within a region around human leukocyte antigen-C spanning 250 kb, termed risk haplotype (RH) 1/2. By re-analyzing a published data set with a previously developed method, the haplotype sharing statistic, we confirm localization of PSORS1 to the RH1 region and refine its location to marker M6S168. We replicate this result in an independent patient sample. The target region harbors fragments of a human endogenous retrovirus K (HERV-K) endogenous retrovirus. Two single-nucleotide polymorphisms with alleles differing between high- and low-risk haplotypes are located within the HERV-K dUTPase. One of these encodes a predicted non-conserved Glu-Arg exchange. The HERV-K dUTPase is expressed in peripheral blood and in normal as well as lesional psoriatic skin. Our results indicate that an endogenous retroviral dUTPase constitutes a candidate gene for the PSORS1 mutation.
authors.affiliation: Klinik für Dermatologie, Charité, Schumannstr., Berlin, Germany. john.foerster@charite.de
authors.forename: John
authors.initials: J
authors.lastname: Foerster
authors.forename: Ilja
authors.initials: I
authors.lastname: Nolte
authors.forename: Judith
authors.initials: J
authors.lastname: Junge
authors.forename: Marcel
authors.initials: M
authors.lastname: Bruinenberg
authors.forename: Susann
authors.initials: S
authors.lastname: Schweiger
authors.forename: Katja
authors.initials: K
authors.lastname: Spaar
authors.forename: Gerrit
authors.initials: G
authors.lastname: van der Steege
authors.forename: Claudia
authors.initials: C
authors.lastname: Ehlert
authors.forename: Marcel
authors.initials: M
authors.lastname: Mulder
authors.forename: Vera
authors.initials: V
authors.lastname: Kalscheuer
authors.forename: Elisa
authors.initials: E
authors.lastname: Blumenthal-Barby
authors.forename: Jennifer
authors.initials: J
authors.lastname: Winter
authors.forename: Petra
authors.initials: P
authors.lastname: Seeman
authors.forename: Markward
authors.initials: M
authors.lastname: Ständer
authors.forename: Wolfram
authors.initials: W
authors.lastname: Sterry
authors.forename: Gerard
authors.initials: G
authors.lastname: Te Meerman
mesh_terms: D002896:Chromosomes, Human, Pair 6; D020077:Endogenous Retroviruses / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000235:genetics*; D011755:Pyrophosphatases / Q000235:genetics*
chemical_list: D015236:HLA-C Antigens; D011755:Pyrophosphatases; C020020:dUTP pyrophosphatase