PURPOSE: To identify loci concerned with radiosensitivity in a mouse model using single nucleotide polymorphism (SNP) markers. MATERIALS AND METHODS: We subjected 276 second filial generation (F2) mice descended from two inbred mouse strains, radiation-induced apoptosis sensitive C57BL/6JNrs (B6) and radiation-induced apoptosis resistant C3H/HeNrs (C3H), to 2.5 Gy whole-body irradiation. We quantified jejunal crypt apoptosis, performed a genome-wide survey, and identified quantitative trait loci (QTL) associated with radiation sensitivity. We expressed apoptosis levels as an apoptotic score (AS), which was equal to the number of apoptotic bodies divided by the number of crypts. We genotyped the mice for 109 SNP markers. RESULTS: AS values were 97.7+/-32.9 in B6 mice and 49.0+/-24.9 in C3H mice (p < 0.01). Genome-wide analysis revealed 8 markers (2 on chromosome 9, 4 on 15, 1 on 17, and 1 on 18) affecting radiation-induced jejunal apoptosis with log odds (LOD) scores ranging from 2.11+/-3.91. We found a significant locus on chromosome 15, which was previously reported by Weil and colleagues. CONCLUSION: These findings support the view that the radiosensitivity of clinically normal tissue depends on variations in several genes.
PURPOSE: To identify loci concerned with radiosensitivity in a mouse model using single nucleotide polymorphism (SNP) markers. MATERIALS AND METHODS: We subjected 276 second filial generation (F2) mice descended from two inbred mouse strains, radiation-induced apoptosis sensitive C57BL/6JNrs (B6) and radiation-induced apoptosis resistant C3H/HeNrs (C3H), to 2.5 Gy whole-body irradiation. We quantified jejunal crypt apoptosis, performed a genome-wide survey, and identified quantitative trait loci (QTL) associated with radiation sensitivity. We expressed apoptosis levels as an apoptotic score (AS), which was equal to the number of apoptotic bodies divided by the number of crypts. We genotyped the mice for 109 SNP markers. RESULTS: AS values were 97.7+/-32.9 in B6 mice and 49.0+/-24.9 in C3H mice (p < 0.01). Genome-wide analysis revealed 8 markers (2 on chromosome 9, 4 on 15, 1 on 17, and 1 on 18) affecting radiation-induced jejunal apoptosis with log odds (LOD) scores ranging from 2.11+/-3.91. We found a significant locus on chromosome 15, which was previously reported by Weil and colleagues. CONCLUSION: These findings support the view that the radiosensitivity of clinically normal tissue depends on variations in several genes.
Authors: Jacqueline P Williams; Stephen L Brown; George E Georges; Martin Hauer-Jensen; Richard P Hill; Amy K Huser; David G Kirsch; Thomas J Macvittie; Kathy A Mason; Meetha M Medhora; John E Moulder; Paul Okunieff; Mary F Otterson; Michael E Robbins; James B Smathers; William H McBride Journal: Radiat Res Date: 2010-04 Impact factor: 2.841