Evidence for complex multigenic inheritance of radiation AML susceptibility in mice revealed using a surrogate phenotypic assay.
Carcinogenesis
; 27(2): 311-8, 2006 Feb.
Article
em En
| MEDLINE
| ID: mdl-16093251
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.
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Base de dados:
MEDLINE
Assunto principal:
Leucemia Induzida por Radiação
/
Leucemia Mieloide
/
Família Multigênica
/
Predisposição Genética para Doença
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article