Further disease genes on chromosomes 16q12 and 1q21
As shown by STR linkage analysis, the PSORIASIS cohort yields linkage with16q. Within that region, CARD15 conferring susceptibility to IBD is located. The complete Kiel cohort was mapped for this region by SNP-genotyping (70 SNP-marker, CARD15 to NOL3). For both psoriasis and psoriasis arthiritis, the major IBD-associated variants of CARD15 have been genotyped. An independent analysis of the 3020INSC frame shift mutation was also performed. A four marker haplotype of CARD15 potentially associated with psoriasis (p< 0.001) was identified. PSORS4, the psoriasis susceptibility gene locus on chromosome 1q21 has been independently confirmed by different genome scans. Although no definitive candidate gene has been implicated yet, the region appears highly promising since it harbours a variety of genes involved in epithelial differentiation in a gene cluster called the Epidermal Differentiation Complex (EDC). For expression profiling experiments, microarryas were established in cooperation with SFB415 (project Z1, Prof. S. Schreiber). Specific arrays of inflammation, cell differentiation, and apoptosis were designed. Methods for extraction of RNA from small amounts of skin tissue were established. Hybridization experiments were performed and several biostatistical methods for evaluation of the hybridization experiments tested. A cDNA bank with labelled cDNA from healthy and affected individuals for further hybridization experiments is available. The preliminary evaluations indicate strong regulatory effects on genes involved in eprodermal differentiation.
