SCANNING CHROMOSOME-17 FOR PSORIASIS SUSCEPTIBILITY - LACK OF EVIDENCE FOR A DISTAL 17Q LOCUS

Evidence for a genetically heterogeneous psoriasis susceptibility locu s on distal human chromosome 17q has recently been reported [Science 1 994;264:1141]. Making use of an independently ascertained collection o f 24 multiplex psoriasis kindreds, we have performed a genotyping scan of chromosome 17 using 12 microsatellite markers and analyzed the dat a using parametric (lod score) as well as novel nonparametric methods, Pairwise lod scores revealed no evidence for linkage to the previousl y implicated marker D17S784 under any of eight models varying in mode of inheritance, penetrance, and sporadic cases. Homogeneous linkage to D17S784 could be excluded under all four autosomal dominant models te sted (Z < -5.8 at Theta = 0.05), and there was no evidence for genetic heterogeneity. All other chromosome 17 markers tested also failed to detect evidence for linkage in any of the kindreds under either a domi nant or a recessive model, Although further analysis using affected si b pair methods provided no statistically significant evidence for link age to any chromosome 17 marker, a cluster of three distal 17q loci di splayed a trend towards greater than expected allele-sharing values (o bserved/expected = 1.10-1.14), These results do not formally confirm t he existence of a psoriasis susceptibility locus on the distal long ar m of human chromosome 17, but are suggestive of its possible involveme nt under a polygenic model, warranting its further investigation in fa milial psoriasis.