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 journalArticle

23 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)311-318
Number of pages8
JournalCarcinogenesis
Volume27
Issue number2
DOIs
StatePublished - Feb 1 2006
Externally publishedYes

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Acute Myeloid Leukemia
Radiation
Chromosomes, Human, Pair 18
Neoplasms
Chromosome Mapping
Radiation Tolerance
Microsatellite Repeats
Biomarkers
Genes

ASJC Scopus subject areas

  • Cancer Research

Cite this

Darakhshan, F., Badie, C., Moody, J., Coster, M., Finnon, R., Finnon, P., ... 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

Evidence for complex multigenic inheritance of radiation AML susceptibility in mice revealed using a surrogate phenotypic assay. / 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, Simon D.

In: Carcinogenesis, Vol. 27, No. 2, 01.02.2006, p. 311-318.

Research output: Contribution to journalArticle

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
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, Simon D. / Evidence for complex multigenic inheritance of radiation AML susceptibility in mice revealed using a surrogate phenotypic assay. In: Carcinogenesis. 2006 ; Vol. 27, No. 2. pp. 311-318.
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