Characterization of the major susceptibility region for psoriasis at chromosome 6p21.3

Psoriasis is a common inflammatory skin condition caused by genetic and env ironmental factors. Recent genome-wide linkage analyses have identified a l ocus encoding susceptibility to psoriasis and placed this gene in the 12 cM interval between markers D6S426 and D6S276 on chromosome 6p21.3. This is a broad region and encompasses the human major histocompatibility complex. W e have sought to localize the susceptibility gene more precisely by exploit ing the linkage, haplotype, and linkage disequilibrium information availabl e through genotyping 118 affected sib pairs, their parents and other affect ed family members. A total of 14 highly polymorphic markers were genotyped, combining anonymous loci with the class I genes HLA-B and -C distributed a cross a genetic interval of approximately 14 cM including the entire major histocompatibility complex. Through the application of higher density mappi ng within the major histocompatibility complex, we identified those regions most commonly shared identical by descent in patients with psoriasis. Usin g the transmission-disequilibrium test, we found significant evidence of li nkage and allelic association across an interval defined by the markers tn6 2 (p = 1.0 x 10(-7)), HLA-B (p = 4.0 x 10(-7)), and HLA-C (p = 2.7 x 10(-9) ), a region encompassed within a 285 kb genomic DNA fragment. Hence these s tudies contribute to the refinement of the localization of a major psoriasi s susceptibility gene and place the critical region near to HLA-C.