Genetic analysis of systemic autoimmunity.

摘要: Even for complex diseases with high rates of monozygotic twin concordance, disease-associated alleles remain elusive. One explanation is that multiple common genetic variants weak effects cause these and identification any single allele requires large cohorts. Conversely, if the allelic spectrum disease heterogeneous, strong rare might be offset by their presence in only a small proportion patient population. Lupus (SLE) systemic autoimmune disease, significant protean clinical manifestations, production high-affinity pathogenic autoantibodies. This phenotype results from genome scans point to molecular defects. Contrary this expectation, our analysis ENU-mutagenized mice indicates homozygous mutations frequently anti-nuclear antibodies (ANAs), can account full blown lupus phenotype. The best characterized example sanroque strain, which develops dsDNA autoantibodies fails censor self-reactive germinal centre T cells. Mapping underlying mutation identified not novel gene, Roquin, but also pathway SLE. Identification such likely identify pathways underlie pathology many patients, lead interacting partners pathology, most effective therapeutic targets.