RGD Reference Report - Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans. - Rat Genome Database

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

Authors: Aitman, TJ  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 
Citation: Aitman TJ, etal., Nature. 2006 Feb 16;439(7078):851-5.
RGD ID: 2293335
Pubmed: PMID:16482158   (View Abstract at PubMed)
DOI: DOI:10.1038/nature04489   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FCGR2AHumancrescentic glomerulonephritis  ISOFcgr2a (Rattus norvegicus)DNA:CNV:3'UTR:RGD 
Fcgr2aRatcrescentic glomerulonephritis  IAGP DNA:CNV:3'UTR:RGD 
Fcgr3Mousecrescentic glomerulonephritis  ISOFcgr2a (Rattus norvegicus)DNA:CNV:3'UTR:RGD 
Glom15Ratglomerulonephritis  IAGP  RGD 
Glom16Ratglomerulonephritis  IAGP  RGD 
Glom22Ratglomerulonephritis  IAGP  RGD 
Glom23Ratglomerulonephritis  IAGP  RGD 
Glom24Ratglomerulonephritis  IAGP  RGD 
Glom25Ratglomerulonephritis  IAGP  RGD 
Glom26Ratglomerulonephritis  IAGP  RGD 
WKY/NCrlRatglomerulonephritis susceptibilityIAGPanti-glomerular basement membrane antibodycompared to LEW and BNRGD 
Glom15Ratnephritis  IAGP  RGD 
Glom16Ratnephritis  IAGP  RGD 
Glom22Ratnephritis  IAGP  RGD 
Glom23Ratnephritis  IAGP  RGD 
Glom24Ratnephritis  IAGP  RGD 
Glom25Ratnephritis  IAGP  RGD 
Glom26Ratnephritis  IAGP  RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Fcgr2aRatregulation of antibody-dependent cellular cytotoxicity  IMP  RGD 
Fcgr2aRatregulation of Fc receptor mediated stimulatory signaling pathway  IMP  RGD 
Fcgr2aRatregulation of phagocytosis  IMP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
WKY/NCrlRatglomerular crescent susceptibilityIAGPanti-glomerular basement membrane antibody RGD 
Glom15Ratglomerulonephritis susceptibilityIDA  RGD 
Glom16Ratglomerulonephritis susceptibilityIDA  RGD 
Glom22Ratglomerulonephritis  IDA  RGD 
Glom23Ratglomerulonephritis  IDA  RGD 
Glom24Ratglomerulonephritis  IDA  RGD 
Glom25Ratglomerulonephritis  IDA  RGD 
Glom26Ratglomerulonephritis  IDA  RGD 
Objects Annotated

Genes (Rattus norvegicus)
Fcgr2a  (Fc gamma receptor 2A)

Genes (Mus musculus)
Fcgr3  (Fc receptor, IgG, low affinity III)

Genes (Homo sapiens)
FCGR2A  (Fc gamma receptor IIa)

QTLs
Glom15  (Glomerulus QTL 15)
Glom16  (Glomerulus QTL 16)
Glom22  (Glomerulus QTL 22)
Glom23  (Glomerulus QTL 23)
Glom24  (Glomerulus QTL 24)
Glom25  (Glomerulus QTL 25)
Glom26  (Glomerulus QTL 26)

Strains
LEW/NHsd  (NA)
WKY/NCrl  (NA)


Additional Information