Correlation between single nucleotide polymorphisms and jejunal crypt cell apoptosis after whole body irradiation

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) an...

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Bibliographic Details
Published in:International journal of radiation biology 2007, Vol.83 (3), p.181-186
Main Authors: Iwata, Masaru, Iwakawa, Mayumi, Noda, Shuhei, Ohta, Toshie, Minfu, Yang, Kimura, Tomo, Shibuya, Hitoshi, Imai, Takashi
Format: Article
Language:English
Subjects:
Animals
Apoptosis - genetics
Apoptosis - radiation effects
Female
Genotype
Inheritance Patterns - radiation effects
intestine
jejunal apoptosis
Jejunum
Lod Score
Male
Mice
Mice, Inbred C3H
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Radiation Tolerance - genetics
Radiation Tolerance - radiation effects
radiosensitivity
SNP
Space life sciences
Whole-Body Irradiation
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Summary: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.
ISSN:0955-3002
1362-3095
DOI:10.1080/09553000601146923