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psors1c1/cdsn single-nucleotide polymorphisms genotypic transmission/disequilibrium test month download article/chapter single-nucleotide polymorphism data lymphocyte-specific transcription complex pedigree disequilibrium test psoriatic arthritis maps transmission/disequilibrium test transmission disequilibrium test human leukocyte antigen human leukocyte antigen stage genome-wide search sequence-specific oligonucleotide probes family-based association study family-based association studies insulin-dependent diabetes mellitus comprehensive case/control caucasian population full article pdf behavior genetics research pui-yan kwok & anne hla-cw12 family members privacy choices/manage cookies fernandez-vina ma major psoriasis-susceptibility locus transmission test family-based analysis extensive linkage disequilibrium runx1 binding site harbored hla-cw12 alleles related subjects disease loci revealed genetic linkage studies psoriasis-susceptibility locus psors1 human corneodesmosin gene european economic area psoriasis-susceptibility loci psoriasis susceptibility loci pui-yan kwok peptide-binding pockets 100-element oligonucleotide array human chromosome 17q gender-related association article helms check access instant access major ethnic groups runx/aml family putative susceptibiltiy gene sharing identical sequences

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         description:Psoriasis is a complex inflammatory disease of the skin affecting 1–2% of the Caucasian population. Associations with alleles from the HLA class I region (now known as PSORS1), particularly HLA-Cw*0602, were described over 20 years ago. However, extensive linkage disequilibrium (LD) within this region has made it difficult to identify the true susceptibility allele from this region. A variety of genes and regions from a 238-kb interval extending from HLA-B to corneodesmosin (CDSN) have been proposed to harbor PSORS1. In order to identify the minimum block of LD in the MHC class I region associated with psoriasis we performed a comprehensive case/control and family-based association study on 242 Northern European psoriasis families and two separate European control populations. High resolution HLA typing of HLA-A, -B and -C alleles was performed, in addition to the genotyping of 18 polymorphic microsatellites and 36 SNPs from a 772-kb segment of the HLA class I region harboring the previously described interval. This corresponded on average to one SNP every 7 kb in the candidate 238 kb region. With all tests, the association was the strongest with single markers and haplotypes from a block of LD harboring HLA-C and SNP n.9. Logistic regression analyses indicated that association seen with candidate genes from the interval such as CDSN and HCR was entirely dependent on association with HLA-Cw*0602 and SNP n.9-G alleles. The previously reported association with CDSN and HCR was observed to be due to the existence of the associated alleles lying on the most commonly over-transmitted haplotype. Rare over-transmitted haplotypes also harbored HLA-Cw*12 alleles. HLA-Cw*12 family members are closely related to HLA Cw*0602, sharing identical sequences in their alpha-2 domains, peptide-binding pockets A, D and E and all 3′ introns. The introduction of a potential binding site for the RUNX/AML family of transcription factors in intron 7, is also specific to these HLA-C alleles. These variants need to be investigated further for their role as PSORS1.
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      headline:Localization of PSORS1 to a haplotype block harboring HLA-C and distinct from corneodesmosin and HCR
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      affiliation:
            name:Washington University School of Medicine
            address:
               name:Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, USA
               type:PostalAddress
            type:Organization
      name:Patricia Taillon-Miller
      affiliation:
            name:Washington University School of Medicine
            address:
               name:Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, USA
               type:PostalAddress
            type:Organization
      name:Shenghui Duan
      affiliation:
            name:Washington University School of Medicine
            address:
               name:Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, USA
               type:PostalAddress
            type:Organization
      name:Derek Gordon
      affiliation:
            name:The Rockeffer University
            address:
               name:Laboratory of Statistical Genetics, The Rockeffer University, New York, USA
               type:PostalAddress
            type:Organization
      name:Brandon Pierce
      affiliation:
            name:Washington University School of Medicine
            address:
               name:Department of Genetics, Washington University School of Medicine, St. Louis, USA
               type:PostalAddress
            type:Organization
      name:Jurg Ott
      affiliation:
            name:The Rockeffer University
            address:
               name:Laboratory of Statistical Genetics, The Rockeffer University, New York, USA
               type:PostalAddress
            type:Organization
      name:John Rice
      affiliation:
            name:Washington University School of Medicine
            address:
               name:Department of Psychiatry, Washington University School of Medicine, St. Louis, USA
               type:PostalAddress
            type:Organization
      name:Marcelo A. Fernandez-Vina
      affiliation:
            name:Georgetown University School of Medicine
            address:
               name:Oncology Department, Georgetown University School of Medicine, Washington, USA
               type:PostalAddress
            type:Organization
            name:The University of Texas M.D. Anderson, Cancer Center
            address:
               name:Department of Laboratory Medicine, The University of Texas M.D. Anderson, Cancer Center, Houston, USA
               type:PostalAddress
            type:Organization
      name:Pui-Yan Kwok
      affiliation:
            name:Washington University School of Medicine
            address:
               name:Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, USA
               type:PostalAddress
            type:Organization
      name:Alan Menter
      affiliation:
            name:Baylor University Medical Center
            address:
               name:Department of Internal Medicine, Division of Dermatology, Baylor University Medical Center, Dallas, USA
               type:PostalAddress
            type:Organization
      name:Anne M. Bowcock
      affiliation:
            name:Washington University School of Medicine
            address:
               name:Department of Genetics, Washington University School of Medicine, St. Louis, USA
               type:PostalAddress
            type:Organization
            name:Washington University School of Medicine
            address:
               name:Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Genetics, Washington University School of Medicine, St. Louis, USA
      name:Department of Genetics, Washington University School of Medicine, St. Louis, USA
      name:Department of Psychiatry, Washington University School of Medicine, St. Louis, USA
      name:Department of Genetics, Washington University School of Medicine, St. Louis, USA
      name:Department of Genetics, Washington University School of Medicine, St. Louis, USA
      name:Oncology Department, Georgetown University School of Medicine, Washington, USA
      name:Department of Laboratory Medicine, The University of Texas M.D. Anderson, Cancer Center, Houston, USA
      name:Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, USA
      name:Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, USA
      name:Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, USA
      name:Laboratory of Statistical Genetics, The Rockeffer University, New York, USA
      name:Department of Genetics, Washington University School of Medicine, St. Louis, USA
      name:Laboratory of Statistical Genetics, The Rockeffer University, New York, USA
      name:Department of Psychiatry, Washington University School of Medicine, St. Louis, USA
      name:Oncology Department, Georgetown University School of Medicine, Washington, USA
      name:Department of Laboratory Medicine, The University of Texas M.D. Anderson, Cancer Center, Houston, USA
      name:Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, USA
      name:Department of Internal Medicine, Division of Dermatology, Baylor University Medical Center, Dallas, USA
      name:Department of Genetics, Washington University School of Medicine, St. Louis, USA
      name:Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, USA
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