Evidence for complex multigenic inheritance of radiation AML susceptibility in mice revealed using a surrogate phenotypic assay

F. Darakhshan; C. Badie; J. Moody; M. Coster; R. Finnon; P. Finnon; A. A. Edwards; M. Szłuińska; C. J. Skidmore; K. Yoshida; R. Ullrich; R. Cox; Simon D. Bouffler

doi:10.1093/carcin/bgi207

Evidence for complex multigenic inheritance of radiation AML susceptibility in mice revealed using a surrogate phenotypic assay

F. Darakhshan
, C. Badie
, J. Moody
, M. Coster
, R. Finnon
, P. Finnon
, A. A. Edwards
, M. Szłuińska
, C. J. Skidmore
, K. Yoshida
, R. Ullrich
, R. Cox
, Simon D. Bouffler

Research output: Contribution to journal › Article › peer-review

29 Scopus citations

Abstract

The mapping of genes which affect individual cancer risk is an important but complex challenge. A surrogate assay of susceptibility to radiation-induced acute myeloid leukaemia (AML) in the mouse based on chromosomal radiosensitivity has been developed and validated. This assay was applied to the mapping of radiation-induced AML risk modifier loci by association with microsatellite markers. A region on chromosome (chr) 18 with strong association is identified and confirmed by backcross analysis. Additional loci on chrs 8 and 13 show significant association. A key candidate gene Rbbp8 on chr18 is identified. Rbbp8 is shown to be upregulated in response to X-irradiation in the AML sensitive CBA strain but not AML resistant C57BL/6 strain. This study demonstrates the strength of utilizing surrogate endpoints of cancer susceptibility in the mapping of mouse loci and identifies additional loci that may affect radiation cancer risk.

Original language	English (US)
Pages (from-to)	311-318
Number of pages	8
Journal	Carcinogenesis
Volume	27
Issue number	2
DOIs	https://doi.org/10.1093/carcin/bgi207
State	Published - Feb 1 2006
Externally published	Yes

ASJC Scopus subject areas

Cancer Research

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10.1093/carcin/bgi207

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Darakhshan, F., Badie, C., Moody, J., Coster, M., Finnon, R., Finnon, P., Edwards, A. A., Szłuińska, M., Skidmore, C. J., Yoshida, K., Ullrich, R., Cox, R., & Bouffler, S. D. (2006). Evidence for complex multigenic inheritance of radiation AML susceptibility in mice revealed using a surrogate phenotypic assay. Carcinogenesis, 27(2), 311-318. https://doi.org/10.1093/carcin/bgi207

Darakhshan, F, Badie, C, Moody, J, Coster, M, Finnon, R, Finnon, P, Edwards, AA, Szłuińska, M, Skidmore, CJ, Yoshida, K, Ullrich, R, Cox, R & Bouffler, SD 2006, 'Evidence for complex multigenic inheritance of radiation AML susceptibility in mice revealed using a surrogate phenotypic assay', Carcinogenesis, vol. 27, no. 2, pp. 311-318. https://doi.org/10.1093/carcin/bgi207

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title = "Evidence for complex multigenic inheritance of radiation AML susceptibility in mice revealed using a surrogate phenotypic assay",

abstract = "The mapping of genes which affect individual cancer risk is an important but complex challenge. A surrogate assay of susceptibility to radiation-induced acute myeloid leukaemia (AML) in the mouse based on chromosomal radiosensitivity has been developed and validated. This assay was applied to the mapping of radiation-induced AML risk modifier loci by association with microsatellite markers. A region on chromosome (chr) 18 with strong association is identified and confirmed by backcross analysis. Additional loci on chrs 8 and 13 show significant association. A key candidate gene Rbbp8 on chr18 is identified. Rbbp8 is shown to be upregulated in response to X-irradiation in the AML sensitive CBA strain but not AML resistant C57BL/6 strain. This study demonstrates the strength of utilizing surrogate endpoints of cancer susceptibility in the mapping of mouse loci and identifies additional loci that may affect radiation cancer risk.",

author = "F. Darakhshan and C. Badie and J. Moody and M. Coster and R. Finnon and P. Finnon and Edwards, \{A. A.\} and M. Sz{\l}ui{\'n}ska and Skidmore, \{C. J.\} and K. Yoshida and R. Ullrich and R. Cox and Bouffler, \{Simon D.\}",

note = "Funding Information: The authors thank Graham Bailey for assisting with statistical analyses. The authors are grateful to Prof. John Todd for providing NOD mice and MRC, Harwell for use of radiation facilities. This work was funded by EU contracts MAGELLANS (FIGH-CT-1999-00035) and RISC-RAD (FI6R-CT-2003-508842). F.D. was supported by an extra-mural research grant to the University of Reading from the National Radiological Protection Board.",

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AU - Darakhshan, F.

AU - Badie, C.

AU - Moody, J.

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AU - Finnon, R.

AU - Finnon, P.

AU - Edwards, A. A.

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AU - Yoshida, K.

AU - Ullrich, R.

AU - Cox, R.

AU - Bouffler, Simon D.

N1 - Funding Information: The authors thank Graham Bailey for assisting with statistical analyses. The authors are grateful to Prof. John Todd for providing NOD mice and MRC, Harwell for use of radiation facilities. This work was funded by EU contracts MAGELLANS (FIGH-CT-1999-00035) and RISC-RAD (FI6R-CT-2003-508842). F.D. was supported by an extra-mural research grant to the University of Reading from the National Radiological Protection Board.

PY - 2006/2/1

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N2 - The mapping of genes which affect individual cancer risk is an important but complex challenge. A surrogate assay of susceptibility to radiation-induced acute myeloid leukaemia (AML) in the mouse based on chromosomal radiosensitivity has been developed and validated. This assay was applied to the mapping of radiation-induced AML risk modifier loci by association with microsatellite markers. A region on chromosome (chr) 18 with strong association is identified and confirmed by backcross analysis. Additional loci on chrs 8 and 13 show significant association. A key candidate gene Rbbp8 on chr18 is identified. Rbbp8 is shown to be upregulated in response to X-irradiation in the AML sensitive CBA strain but not AML resistant C57BL/6 strain. This study demonstrates the strength of utilizing surrogate endpoints of cancer susceptibility in the mapping of mouse loci and identifies additional loci that may affect radiation cancer risk.

AB - The mapping of genes which affect individual cancer risk is an important but complex challenge. A surrogate assay of susceptibility to radiation-induced acute myeloid leukaemia (AML) in the mouse based on chromosomal radiosensitivity has been developed and validated. This assay was applied to the mapping of radiation-induced AML risk modifier loci by association with microsatellite markers. A region on chromosome (chr) 18 with strong association is identified and confirmed by backcross analysis. Additional loci on chrs 8 and 13 show significant association. A key candidate gene Rbbp8 on chr18 is identified. Rbbp8 is shown to be upregulated in response to X-irradiation in the AML sensitive CBA strain but not AML resistant C57BL/6 strain. This study demonstrates the strength of utilizing surrogate endpoints of cancer susceptibility in the mapping of mouse loci and identifies additional loci that may affect radiation cancer risk.

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Evidence for complex multigenic inheritance of radiation AML susceptibility in mice revealed using a surrogate phenotypic assay

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