| Authors: | Darakhshan F, Badie C, Moody J, Coster M, Finnon R, Finnon P, Edwards AA, Szluinska M, Skidmore CJ, Yoshida K, Ullrich R, Cox R, Bouffler SD |
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| Title: | Evidence for complex multigenic inheritance of radiation AML susceptibility in mice revealed using a surrogate phenotypic assay. |
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| Journal: | Carcinogenesis
Feb 2006 , Vol 27 , pp. 311-8 |
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| 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.
PUBMED: 16093251
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| Ontological Annotations: |
- D015415: Biological Markers (Publication, NCBO Annotator)
- D015211: Zellweger Syndrome (Publication, NCBO Annotator)
- D009369: Neoplasms (Publication, NCBO Annotator)
- D002875: Chromosomes (Publication, NCBO Annotator)
- D051379: Mice (Publication, NCBO Annotator)
- D011827: Radiation (Publication, NCBO Annotator)
- D014918: Wills (Publication, NCBO Annotator)
- D012306: Risk (Publication, NCBO Annotator)
- GO:0005694: chromosome (Publication, NCBO Annotator)
- D000339: Affect (Publication, NCBO Annotator)
- D011836: Radiation Tolerance (Publication, NCBO Annotator)
- D001244: Association (Publication, NCBO Annotator)
- D018895: Microsatellite Repeats (Publication, NCBO Annotator)
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