Gene for Familial Psoriasis Susceptibility Mapped to the Distal End of Human Chromosome 17q

Abstract

A gene involved in psoriasis susceptibility was localized to the distal region of human chromosome 17q as a result of a genome-wide linkage analysis with polymorphic microsatellites and eight multiply affected psoriasis kindreds. In the family which showed the strongest evidence for linkage, the recombination fraction between a psoriasis susceptibility locus and D17S784 was 0.04 with a maximum two-point lod score of 5.33. There was also evidence for genetic heterogeneity and although none of the linked families showed any association with HLA-Cw6, two unlinked families showed weak levels of association. This study demonstrates that in some families, psoriasis susceptibility is due to variation at a single major genetic locus other than the human lymphocyte antigen locus.

The Non-MHC Quantitative Trait LocusCia5Contains Three Major Arthritis Genes That Differentially Regulate Disease Severity, Pannus Formation, and Joint Damage in Collagen- and Pristane-Induced Arthritis

“…Cia5a and Cia5d also colocalize with several loci, or their syntenic regions, implicated in the regulation of rodent models of autoimmunity and inflammation (35-37, 60 -62), or in the susceptibility to human autoimmune diseases (63)(64)(65)(66). These studies suggest that both Cia5a and Cia5d genes could be relevant not only to arthritis, but also to other autoimmune diseases.…”

Combined segregation and linkage analysis of HLA markers in familial psoriasis

“…21 However, some of these scans found no evidence for linkage to HLA. 15,16,20 We subsequently showed that the evidence for linkage to HLA is markedly increased when linkage disequilibrium information is taken into account. 11,12 Recently, PSORS1 has been fine-mapped to the vicinity of HLA-C by linkage disequilibrium mapping.…”

Cytogenetic analysis of 477 psoriatics revealed an increased frequency of aberrations involving chromosome region 11q

“…2 The genetic linkage analyses presented so far also indicate several possible non-HLA gene locations, all of which have not been confirmed. [2][3][4][5][6] Two of these studies using a few large pedigrees presented data suggesting a psoriasis susceptibility locus on 17q and 4q respectively. 3,4 Trembath et al 2 recently reported a genome scan of 66 affected sib pairs in which four potential psoriasis susceptibility loci were identified, on chromosome 2p, 6p (HLA region), 8q and 20p.…”

“…[2][3][4][5][6] Two of these studies using a few large pedigrees presented data suggesting a psoriasis susceptibility locus on 17q and 4q respectively. 3,4 Trembath et al 2 recently reported a genome scan of 66 affected sib pairs in which four potential psoriasis susceptibility loci were identified, on chromosome 2p, 6p (HLA region), 8q and 20p. Nair et al 5 confirmed the locus in the HLA region and presented two additional novel loci on chromosome 16q and 20p using 182 sib pairs in a genome-wide scan.…”