Outside of the MHC, genome-wide linkage scans generated conflicting results (Capon et al. Functional studies demonstrated that one disease associated variant affected the stability of CDSN mRNA (Capon et al. In an attempt to overcome this difficulty, the entire PSORS1 region was sequenced in individuals bearing different HLA-C alleles, with a view to identifying Single Nucleotide Polymorphisms (SNPs) that were unique to the PSORS1 risk haplotype. The field of psoriasis genetics has embraced these advances and nine GWAS have been carried out in the last few years (Capon et al. The linkage analysis has been used to identify multiple loci and alleles that confer risk of the disease. Other studies, using genome-wide analytical techniques, tried to link the disease to copy number variants (CNVs) that are segments of DNA ranging in size from kilobases to megabases that vary in copy number. Additional studies would include associated gene expression variations with either SNPs or CNVs. List of cytokines involved in psoriasis pathogenesis with chromosomal location. 2001;9:7785. Genome-wide linkage scans have identified multiple loci linked to each disease and revealed overlap with psoriasis and atopic dermatitis susceptibility loci on chromosomes 1q21, 3q21, 17q25 and 20p12. Patients with psoriasis also have different clinical features depending on whether they are HLA-Cw6 positive or negative. Moreover, SLC9A3R1, from chromosome 17q25, is associated with psoriasis (55) and binds the solute carrier SLC9A3 (solute carrier family 9, isoform 3 or NHE3), a sodium/hydrogen exchanger.
Classic genomewide linkage analysis has identified nine locations (loci) on different chromosomes associated with psoriasis. They are called psoriasis susceptibility 1 through 9 (PSORS1 through PSORS9). PSOR1 locus (6q21) has been strongly associated with psoriasis; however, it is difficult to identify additional independent association due to strong linkage disequilibrium in the MHC region. Genome-wide linkage analyses have identified nine susceptibility loci (PSORS1 9), only one locus has been consistently replicated. The classical MHC locus encompasses approximately 3.6 megabase pairs (Mb) on 6p21. SNP for a conditional analysis can vary, consequently may lead to different results. Psoriasis is a long-lasting autoimmune disease characterized by patches of abnormal skin. Psoriasis is associated with an increased risk of psoriatic arthritis, lymphomas, cardiovascular disease, Crohn’s disease, and depression. Classic genome-wide linkage analysis has identified nine loci on different chromosomes associated with psoriasis. PSORS1 is located on chromosome 6 in the major histocompatibility complex (MHC), which controls important immune functions.
Classic genome wide linkage analysis has identified nine locations (loci) on different chromosomes associated with psoriasis. They are called psoriasis susceptibility 1 through 9 ( PSORS1 through PSORS9). Psoriatic arthritis (PsA), an inflammatory joint disease associated with psoriasis, is a heterogeneous disease with various patterns such as mild mono-oligoarthritis or very severe, erosive and destructive polyarthritis indistinguishable from rheumatoid arthritis (RA), or spondyloarthropathy with axial engagement1. Based on these studies several disease susceptibility loci on different chromosomes have been proposed. Gene expression changes in psoriasis lesions have been well documented, and strongly support an important role for tumor necrosis factor and interferon gamma signal pathways in its pathogenesis. The strongest genetic determinant of psoriasis identified to date lies within the class I region of the multiple histocompatibility locus antigen cluster, although its low penetrance implicates a requirement for other genetic risk factors. Multiple genome-wide linkage and an increasing number of association studies have been carried out, leading to multiple linkage peaks, and the identification of potential low risk variants. (e.g. a locus on chromosome 18p identified with linkage analyses in the Finnish population).
The therapeutic effect of immunosuppressive agents suggests psoriasis has a primary immune pathogenic basis. A number of genetic studies have sought to identify the psoriasis susceptibility loci. 7 Subsequently, genome-wide linkage scans have mapped psoriasis to several chromosomal regions including PSORS1 at 6p21,8,9 PSORS2 at 17q,8 10 PSORS3 at 4q,11 PSORS4 at 1q,12 PSORS5 at 3q,13 PSORS6 at 19p,14 and PSORS7 at 1p. Multipoint linkage analysis with 45 SNP markers near the 17q terminus. Classic genome-wide linkage analysis has identified nine loci on different chromosomes associated with psoriasis. They are called psoriasis susceptibility 1 through 9 (PSORS1 through PSORS9). At least 33 different candidate genes for vitiligo have been reported on the basis of such studies (Birlea et al. Normally, genetic loci discovered through genome-wide linkage studies encompass several megabases. GV and nine SNPs in the region spanning UBASH3A on chromosome 21q22.3; The HLA class I region of chromosome 6p21.3 where PSORS1 resides. Psoriasis is a long- lasting autoimmune disease characterized by patches of abnormal skin. Classic genome- wide linkage analysis has identified nine loci on different chromosomes associated with psoriasis.