Molecular genetic analysis of Psoriasis vulgaris
thesisposted on 15.12.2014, 10:38 by Richard Lee. Clough
In an attempt to identify the genetic determinants of psoriasis a genome wide screen (GWS) with microsatellites was performed on a collection of multiplex families. Ten microsatellites were identified that generated evidence of linkage to psoriasis susceptibility loci. Support of linkage was observed to markers in the major histocompatibility complex (MHC) and to markers on chromosomes 2, 8 and 20 in an independent collection of families.;These data indicated that the primary genetic determinant for psoriasis was located in the MHC, a region historically observed to be associated with psoriasis in case/control studies. Fine mapping of this region has produced strong evidence that the susceptibility locus lies within a 285 kb region defined by HLA-C and the microsatellite TN62.;The three non-MHC linkages were screened in a large collection of ASP families, although none received additional support of linkage. The families were partitioned upon the basis of allele sharing at the MHC. Those families that exhibited linkage to the MHC (TN3 families) generated evidence of linkage to chromosome 20, suggesting an interaction between the susceptibility locus in this interval with the major locus in the MHC. A YAC contig was constructed for this region and two candidate genes were excluded from this interval. Two novel microsatellites were cloned from this contig although neither failed to generate evidence of linkage or association to a susceptibility gene.;A secondary GWS was performed upon a large collection of families, although this failed to generate evidence of linkage to any novel susceptibility loci or to provide support for previously identified putative loci, except to markers on the MHC. Upon partitioning of this dataset, the TN3 families generated evidence of linkage to markers on chromosome 1. Those families not exhibiting linkage to the MHC (TNX families) generated evidence of linkage to three further novel regions.