A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease

Yasunori Ogura; Denise K. Bonen; Naohiro Inohara; Dan L. Nicolae; Felicia F. Chen; Richard Ramos; Heidi Britton; Thomas Moran; Reda Karaliuskas; Richard H. Duerr; Jean Paul Achkar; Steven R. Brant; Theodore M. Bayless; Barbara S. Kirschner; Stephen B. Hanauer; Gabriel Nũez; Judy H. Cho

doi:10.1038/35079114

A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease

Yasunori Ogura, Denise K. Bonen, Naohiro Inohara, Dan L. Nicolae, Felicia F. Chen, Richard Ramos, Heidi Britton, Thomas Moran, Reda Karaliuskas, Richard H. Duerr, Jean Paul Achkar, Steven R. Brant, Theodore M. Bayless, Barbara S. Kirschner, Stephen B. Hanauer, Gabriel Nũez, Judy H. Cho

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Abstract

Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract, which is thought to result from the effect of environmental factors in a genetically predisposed host. A gene location in the pericentromeric region of chromosome 16, IBD1, that contributes to susceptibility to Crohn's disease has been established through multiple linkage studies, but the specific gene(s) has not been identified. NOD2, a gene that encodes a protein with homology to plant disease resistance gene products is located in the peak region of linkage on chromosome 16 (ref. 7). Here we show, by using the transmission disequilibium test and case-control analysis, that a frameshift mutation caused by a cytosine insertion, 3020insC, which is expected to encode a truncated NOD2 protein, is associated with Crohn's disease. Wild-type NOD2 activates nuclear factor NF-κB, making it responsive to bacterial lipopolysaccharides; however, this induction was deficient in mutant NOD2. These results implicate NOD2 in susceptibility to Crohn's disease, and suggest a link between an innate immune response to bacterial components and development of disease.

Original language	English (US)
Pages (from-to)	603-606
Number of pages	4
Journal	Nature
Volume	411
Issue number	6837
DOIs	https://doi.org/10.1038/35079114
State	Published - May 31 2001
Externally published	Yes

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Ogura, Y., Bonen, D. K., Inohara, N., Nicolae, D. L., Chen, F. F., Ramos, R., Britton, H., Moran, T., Karaliuskas, R., Duerr, R. H., Achkar, J. P., Brant, S. R., Bayless, T. M., Kirschner, B. S., Hanauer, S. B., Nũez, G., & Cho, J. H. (2001). A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature, 411(6837), 603-606. https://doi.org/10.1038/35079114

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title = "A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease",

abstract = "Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract, which is thought to result from the effect of environmental factors in a genetically predisposed host. A gene location in the pericentromeric region of chromosome 16, IBD1, that contributes to susceptibility to Crohn's disease has been established through multiple linkage studies, but the specific gene(s) has not been identified. NOD2, a gene that encodes a protein with homology to plant disease resistance gene products is located in the peak region of linkage on chromosome 16 (ref. 7). Here we show, by using the transmission disequilibium test and case-control analysis, that a frameshift mutation caused by a cytosine insertion, 3020insC, which is expected to encode a truncated NOD2 protein, is associated with Crohn's disease. Wild-type NOD2 activates nuclear factor NF-κB, making it responsive to bacterial lipopolysaccharides; however, this induction was deficient in mutant NOD2. These results implicate NOD2 in susceptibility to Crohn's disease, and suggest a link between an innate immune response to bacterial components and development of disease.",

author = "Yasunori Ogura and Bonen, {Denise K.} and Naohiro Inohara and Nicolae, {Dan L.} and Chen, {Felicia F.} and Richard Ramos and Heidi Britton and Thomas Moran and Reda Karaliuskas and Duerr, {Richard H.} and Achkar, {Jean Paul} and Brant, {Steven R.} and Bayless, {Theodore M.} and Kirschner, {Barbara S.} and Hanauer, {Stephen B.} and Gabriel Nũez and Cho, {Judy H.}",

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doi = "10.1038/35079114",

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AU - Ogura, Yasunori

AU - Bonen, Denise K.

AU - Inohara, Naohiro

AU - Nicolae, Dan L.

AU - Chen, Felicia F.

AU - Ramos, Richard

AU - Britton, Heidi

AU - Moran, Thomas

AU - Karaliuskas, Reda

AU - Duerr, Richard H.

AU - Achkar, Jean Paul

AU - Brant, Steven R.

AU - Bayless, Theodore M.

AU - Kirschner, Barbara S.

AU - Hanauer, Stephen B.

AU - Nũez, Gabriel

AU - Cho, Judy H.

PY - 2001/5/31

Y1 - 2001/5/31

N2 - Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract, which is thought to result from the effect of environmental factors in a genetically predisposed host. A gene location in the pericentromeric region of chromosome 16, IBD1, that contributes to susceptibility to Crohn's disease has been established through multiple linkage studies, but the specific gene(s) has not been identified. NOD2, a gene that encodes a protein with homology to plant disease resistance gene products is located in the peak region of linkage on chromosome 16 (ref. 7). Here we show, by using the transmission disequilibium test and case-control analysis, that a frameshift mutation caused by a cytosine insertion, 3020insC, which is expected to encode a truncated NOD2 protein, is associated with Crohn's disease. Wild-type NOD2 activates nuclear factor NF-κB, making it responsive to bacterial lipopolysaccharides; however, this induction was deficient in mutant NOD2. These results implicate NOD2 in susceptibility to Crohn's disease, and suggest a link between an innate immune response to bacterial components and development of disease.

AB - Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract, which is thought to result from the effect of environmental factors in a genetically predisposed host. A gene location in the pericentromeric region of chromosome 16, IBD1, that contributes to susceptibility to Crohn's disease has been established through multiple linkage studies, but the specific gene(s) has not been identified. NOD2, a gene that encodes a protein with homology to plant disease resistance gene products is located in the peak region of linkage on chromosome 16 (ref. 7). Here we show, by using the transmission disequilibium test and case-control analysis, that a frameshift mutation caused by a cytosine insertion, 3020insC, which is expected to encode a truncated NOD2 protein, is associated with Crohn's disease. Wild-type NOD2 activates nuclear factor NF-κB, making it responsive to bacterial lipopolysaccharides; however, this induction was deficient in mutant NOD2. These results implicate NOD2 in susceptibility to Crohn's disease, and suggest a link between an innate immune response to bacterial components and development of disease.

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A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease

Abstract

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