Multilocus inheritance determines predisposition to α‐radiation induced bone tumourigenesis in mice

摘要: In a recent study, we presented evidence for genetic predisposition governing radiation osteosarcomagenesis in mice. Following the incorporation of bone-seeking α emitter 227Th, ˜25% variance osteosarcoma incidence was determined by inherited factors. We have now mapped 5 susceptibility loci crosses between more susceptible BALB/c and resistant CBA/Ca strains. The major QTL on chromosome 14 overlaps with locus that already found our previous using different strains Here, investigate effect which 4 minor modifier interact to influence predisposition. isotope, 100% mice harbour high-risk genotypes at all develop an average 472 days latency times. 10 inheriting exclusively low-risk only 1 found, arising after 733 time. Inheritance distinct combinations alleles confer extreme phenotypes terms or resistance than observed either two parental inbred From present demonstrate additive effects multiple alleles, each making phenotypic contribution, can combine significantly alter tumour risk. This mechanism be particular importance genetically heterogeneous populations such as man. © 2005 Wiley-Liss, Inc.