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

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Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans. / Aitman, Timothy J.; Dong, Rong; Vyse, Timothy J. et al.
In: Nature, Vol. 439, 16.02.2006, p. 851-855.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Aitman, TJ, Dong, R, Vyse, TJ, Norsworthy, PJ, Johnson, MD, Smith, J, Mangion, J, Roberton-Lowe, C, Marshall, AJ, Petretto, E, Hodges, M, Bhangal, G, Patel, SG, Sheehan-Rooney, K, Duda, M, Cook, PR, Evans, DJ, Domin, J, Flint, J, Boyle, JJ, Pusey, CD & Cook, HT 2006, 'Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans', Nature, vol. 439, pp. 851-855. https://doi.org/10.1038/nature04489

APA

Aitman, T. J., Dong, R., Vyse, T. J., Norsworthy, P. J., Johnson, M. D., Smith, J., Mangion, J., Roberton-Lowe, C., Marshall, A. J., Petretto, E., Hodges, M., Bhangal, G., Patel, S. G., Sheehan-Rooney, K., Duda, M., Cook, P. R., Evans, D. J., Domin, J., Flint, J., ... Cook, H. T. (2006). Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans. Nature, 439, 851-855. https://doi.org/10.1038/nature04489

Vancouver

Aitman TJ, Dong R, Vyse TJ, Norsworthy PJ, Johnson MD, Smith J et al. Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans. Nature. 2006 Feb 16;439:851-855. doi: 10.1038/nature04489

Author

Aitman, Timothy J. ; Dong, Rong ; Vyse, Timothy J. et al. / Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans. In: Nature. 2006 ; Vol. 439. pp. 851-855.

Bibtex

@article{dd38f68f2e394331b1d2033ee4ad759c,
title = "Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans",
abstract = "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 genetics1, 2, 3. 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 variation3, 4, 5. 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.",
keywords = "copy number polymorphism, Fcgr3, glomerulonephritis",
author = "Aitman, {Timothy J.} and Rong Dong and Vyse, {Timothy J.} and Norsworthy, {Penny J.} and Johnson, {Michelle D.} and Jennifer Smith and Jonathan Mangion and Cheri Roberton-Lowe and Marshall, {Amy J.} and Enrico Petretto and Matt Hodges and Gurjeet Bhangal and Patel, {Sheetal G.} and Kelly Sheehan-Rooney and Mark Duda and Cook, {Paul R.} and Evans, {David J.} and Jan Domin and Jonathan Flint and Boyle, {Joseph J.} and Pusey, {Charles D.} and Cook, {H. Terence}",
year = "2006",
month = feb,
day = "16",
doi = "10.1038/nature04489",
language = "English",
volume = "439",
pages = "851--855",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",

}

RIS

TY - JOUR

T1 - Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans

AU - Aitman, Timothy J.

AU - Dong, Rong

AU - Vyse, Timothy J.

AU - Norsworthy, Penny J.

AU - Johnson, Michelle D.

AU - Smith, Jennifer

AU - Mangion, Jonathan

AU - Roberton-Lowe, Cheri

AU - Marshall, Amy J.

AU - Petretto, Enrico

AU - Hodges, Matt

AU - Bhangal, Gurjeet

AU - Patel, Sheetal G.

AU - Sheehan-Rooney, Kelly

AU - Duda, Mark

AU - Cook, Paul R.

AU - Evans, David J.

AU - Domin, Jan

AU - Flint, Jonathan

AU - Boyle, Joseph J.

AU - Pusey, Charles D.

AU - Cook, H. Terence

PY - 2006/2/16

Y1 - 2006/2/16

N2 - 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 genetics1, 2, 3. 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 variation3, 4, 5. 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.

AB - 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 genetics1, 2, 3. 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 variation3, 4, 5. 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.

KW - copy number polymorphism

KW - Fcgr3

KW - glomerulonephritis

U2 - 10.1038/nature04489

DO - 10.1038/nature04489

M3 - Journal article

VL - 439

SP - 851

EP - 855

JO - Nature

JF - Nature

SN - 0028-0836

ER -