1. Low-penetrance genetic susceptibility and resistance loci implicated in the relative risk for radiation-induced acute myeloid leukemia in mice
- Author
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Roger T. Snowden, A.L. Knight, Mark Plumb, Helen Cleary, Emma Boulton, and Clare Cole
- Subjects
Risk ,Myeloid ,Genotype ,Genetic Linkage ,Immunology ,Locus (genetics) ,Penetrance ,Biology ,Biochemistry ,Mice ,Genetic linkage ,hemic and lymphatic diseases ,medicine ,Animals ,Genetic Predisposition to Disease ,Inbreeding ,Genetics ,Leukemia, Radiation-Induced ,Mice, Inbred BALB C ,Myeloid leukemia ,Cell Biology ,Hematology ,medicine.disease ,Molecular biology ,Mice, Inbred C57BL ,Leukemia ,Haematopoiesis ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,Mice, Inbred DBA ,Mice, Inbred CBA ,Bone marrow ,Stem cell - Abstract
Inbred CBA/H mice are susceptible to radiation-induced acute myeloid leukemia (r-AML), and C57BL/6 mice are resistant. A genome-wide screen for linkage between genotype and phenotype (r-AML) of 67 affected (CBA/H × C57BL/6)F1 × CBA/H backcross mice has revealed at least 2 suggestive loci that contribute to the overall lifetime risk for r-AML. Neither is necessary or sufficient for r-AML, but relative risk is the net effect of susceptibility (distal chromosome 1) and resistance (chromosome 6) loci. An excess of chromosome 6 aberrations in mouse r-AML and bone marrow cells up to 6 months after irradiation in vivo suggests the locus confers a proliferative advantage during the leukemogenic process. The stem cell frequency regulator 1 (Scfr1) locus maps to distal chromosome 1 and determines the frequency of hemopoietic stem cells (HSCs) in inbred mice, suggesting that target size may be one factor in determining the relative susceptibility of inbred mice to r-AML.
- Published
- 2002