Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans

摘要: Glomerulonephritis is a kidney inflammation that occurs alone or as part of other conditions, including the autoimmune disorder lupus. A novel mutation has now been identified cause disease in rat model. The affects Fcgr3 immunoglobulin receptor, but it does not produce defective receptor. Rather, too many copies an otherwise normal gene are produced. similar gene-number defect was then detected subset human systemic lupus erythematosus patients with inflammation. In these equivalent receptor gene, FCGR3B, present at low copy number. Disease seems to result when number altered either direction, so levels must need be very finely tuned. Identification genes underlying complex phenotypes and definition evolutionary forces have shaped eukaryotic genomes among current challenges molecular genetics1,2,3. Variation increasingly recognized source inter-individual differences genome sequence proposed driving force for evolution phenotypic variation3,4,5. Here we show variation orthologous determinant susceptibility immunologically mediated glomerulonephritis. Positional cloning loss newly described, rat-specific paralogue, Fcgr3-related (Fcgr3-rs), macrophage overactivity glomerulonephritis Wistar Kyoto rats. humans, orthologue Fcgr3, associated erythematosus. finding polymorphism predisposes renal two mammalian species provides direct evidence importance plasticity genetically phenotypes, common disease.