Journal Article

Identification of a Major Susceptibility Locus on Chromosome 6p and Evidence for Further Disease Loci Revealed by a Two Stage Genome-Wide Search in Psoriasis

Richard C. Trembath, R. Lee Clough, Jane L. Rosbotham, Andrew B. Jones, Richard D. R. Camp, Angela Frodsham, Julie Browne, Ruth Barber, Joseph Terwilliger, G. Mark Lathrop and Jonathan N. W. N. Barker

in Human Molecular Genetics

Volume 6, issue 5, pages 813-820
Published in print May 1997 | ISSN: 0964-6906
Published online May 1997 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/6.5.813
Identification of a Major Susceptibility Locus on Chromosome 6p and Evidence for Further Disease Loci Revealed by a Two Stage Genome-Wide Search in Psoriasis

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Psoriasis is a common chronic inflammatory disorder of the skin. To further understand the pathogenesis of psoriasis we have chosen to investigate the molecular genetic basis of the disorder. We have used a two-stage approach to search the human genome for the location of genes conferring susceptibility to psoriasis, using a total of 106 affected sibling pairs identified from 68 independent families. As over a third of the extended kindreds included affected relatives besides siblings, in addition to an analysis of allele sharing between affected sibling pairs, a novel linkage strategy was applied that extracts full non-parametric information. Four principal regions of possible linkage were identified on chromosomes 2, 8, 20 (p <0.005) and markers from the MHC region at 6p21 (p <0.0000006) for which significant evidence of linkage disequilibrium was also observed (p<0.00002). Whilst data from limited case control associations exist to implicate the MHC, the results of this genome wide analysis demonstrate that, at least in the population studied, a gene or genes located within the MHC and close to the class 1 HLA loci, represent the major determinant of the genetic basis of psoriasis.

Journal Article.  4979 words.  Illustrated.

Subjects: Genetics and Genomics

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