Correlation between single nucleotide polymorphisms and jejunal crypt cell apoptosis after whole body irradiation.
OBJECTIVE
To identify loci concerned with radiosensitivity in a mouse model using single nucleotide polymorphism (SNP) markers.


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.


CONCLUSIONS
These findings support the view that the radiosensitivity of clinically normal tissue depends on variations in several genes.
Iwata
Masaru
M
Radgenomics Project, Frontier Research Center, National Institute of Radiological Sciences, Japan.
Iwakawa
Mayumi
M
Noda
Shuhei
S
Ohta
Toshie
T
Minfu
Yang
Y
Kimura
Tomo
T
Shibuya
Hitoshi
H
Imai
Takashi
T
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects*; D005260:Female; D005838:Genotype; D040582:Inheritance Patterns / Q000528:radiation effects; D007583:Jejunum; D008126:Lod Score; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D011836:Radiation Tolerance / Q000235:genetics / Q000528:radiation effects; D014916:Whole-Body Irradiation