Haplotype Sharing Analysis Identifies a Retroviral dUTPase as Candidate Susceptibility Gene for Psoriasis John Foerster, Ilja Nolte, Judith Junge, Marcel.

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Haplotype Sharing Analysis Identifies a Retroviral dUTPase as Candidate Susceptibility Gene for Psoriasis John Foerster, Ilja Nolte, Judith Junge, Marcel Bruinenberg, Susann Schweiger, Katja Spaar, Gerrit van der Steege, Claudia Ehlert, Marcel Mulder, Vera Kalscheuer, Elisa Blumenthal-Barby, Jennifer Winter, Petra Seeman, Markward Ständer, Wolfram Sterry, Gerard te Meerman Journal of Investigative Dermatology Volume 124, Issue 1, Pages 99-102 (January 2005) DOI: 10.1111/j.0022-202X.2004.23504.x Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Haplotype-sharing statistic (HSS) re-analysis of haplotype clusters fromNair et al (2000). The x-axis shows markers from (Nair et al, 2000) telomere to centromere, beginning at marker D6S273. (A) HSS analysis, quantifying excess in mean haplotype length shared among patient haplotypes around each marker as compared with that among control haplotypes. The horizontal dashed lines represent PSORS1, the risk haplotype (RH)1/RH2 risk interval, respectively. (B) Directional analysis quantifying excess in mean haplotype length shared among patients as compared with controls only telomeric (solid line) or only centromeric (dashed line) from each marker. The arrowhead marking the intersection of both curves indicates the most likely interval harboring the PSORS1 mutation. Journal of Investigative Dermatology 2005 124, 99-102DOI: (10.1111/j.0022-202X.2004.23504.x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Expression of the human endogenous retrovirus K (HERVK) dUTPase at the PSORS1locus. (A) Peripheal blood from psoriasis patients (upper panel) or healthy donors (lower panel). RT-PCR was performed from total RNA with primers specific for the dUTPase open reading frame (ORF) or β-actin. “+” and “-” indicate cDNA synthesis performed in the presence or absence of reverse transcriptase, respectively. The expected size of the PSORS1 dUTPase band is 430 bp and that of β-actin is 466 bp. (B) Detection of the PSORS1 dUTPase in polyA+ RNA from peripheral blood mononuclear cells from a healthy donor, performed as in (A). (C) Detection of the dUTPase ORF at PSORS1 in skin by nested RT-PCR as detailed in online methods from two independent psoriatic plaque samples (pso L 1.2), non-lesional skin, and skin from a healthy proband (con skin). The expected size of the nested RT-PCR PSORS1 dUTPase product is 260 bp. Journal of Investigative Dermatology 2005 124, 99-102DOI: (10.1111/j.0022-202X.2004.23504.x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions