1. Nature. 2006 Feb 16;439(7078):851-5.
Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and
humans.
Aitman TJ(1), Dong R, Vyse TJ, Norsworthy PJ, Johnson MD, Smith J, Mangion J,
Roberton-Lowe C, Marshall AJ, Petretto E, Hodges MD, Bhangal G, Patel SG,
Sheehan-Rooney K, Duda M, Cook PR, Evans DJ, Domin J, Flint J, Boyle JJ, Pusey
CD, Cook HT.
Author information:
(1)Physiological Genomics and Medicine Group, MRC Clinical Sciences Centre,
Imperial College, London W12 0NN, UK. t.aitman@csc.mrc.ac.uk
Comment in
Nature. 2006 Feb 16;439(7078):798-9.
Identification of the genes underlying complex phenotypes and the definition of
the evolutionary forces that have shaped eukaryotic genomes are among the current
challenges in molecular genetics. Variation in gene copy number is increasingly
recognized as a source of inter-individual differences in genome sequence and has
been proposed as a driving force for genome evolution and phenotypic variation.
Here we show that copy number variation of the orthologous rat and human Fcgr3
genes is a determinant of susceptibility to immunologically mediated
glomerulonephritis. Positional cloning identified loss of the newly described,
rat-specific Fcgr3 paralogue, Fcgr3-related sequence (Fcgr3-rs), as a determinant
of macrophage overactivity and glomerulonephritis in Wistar Kyoto rats. In
humans, low copy number of FCGR3B, an orthologue of rat Fcgr3, was associated
with glomerulonephritis in the autoimmune disease systemic lupus erythematosus.
The finding that gene copy number polymorphism predisposes to immunologically
mediated renal disease in two mammalian species provides direct evidence for the
importance of genome plasticity in the evolution of genetically complex
phenotypes, including susceptibility to common human disease.
PMID: 16482158 [PubMed - indexed for MEDLINE]
PUBMED: 16482158
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