A genome scanning approach to assess the genetic effects of radiation in mice and humans.
We used Restriction Landmark Genome Scanning (RLGS) to assess, on a genome-wide basis, the mutation induction rate in mouse germ cells after radiation exposure. Analyses of 1,115 autosomal NotI DNA fragments per mouse for reduced spot intensity, indicative of loss of one copy, in 506 progeny derived from X-irradiated spermatogonia (190, 237 and 79 mice in 0-, 3-, and 5-Gy groups, respectively), permitted us to identify 16 mutations affecting 23 fragments in 20 mice. The 16 mutations were composed of eight small changes (1-9 bp) at microsatellite sequences, five large deletions (more than 25 kb), and three insertions of SINE B2 or LINE1 transposable elements. The maximum induction rate of deletion mutations was estimated as (0.17 +/- 0.09) x 10(-5)/locus Gy(-1). The estimate is considerably lower than 1 x 10(-5)/locus Gy(-1), the mean induction rate of deletion mutations at Russell's 7 loci, which assumed that deletion mutations comprise 50% of all mutations. We interpret the results as indicating that the mean induction rate of mutations in the whole genome may be substantially lower than that at the 7 loci. We also demonstrate the applicability of RLGS for detection of human mutations, which allows direct comparisons between the two species.
Asakawa
Jun-ichi
J
Department of Genetics, Radiation Effects Research Foundation, 5-2 Hijiyama-Park, Minami-ku, Hiroshima 732-0815, Japan. jun@rerf.or.jp
Kuick
Rork
R
Kodaira
Mieko
M
Nakamura
Nori
N
Katayama
Hiroaki
H
Pierce
Donald
D
Funamoto
Sachiyo
S
Preston
Dale
D
Satoh
Chiyoko
C
Neel
James V
JV
Hanash
Samir
S
D000818:Animals; D002461:Cell Line, Transformed; D004247:DNA / Q000528:radiation effects*; D005260:Female; D017353:Gene Deletion; D005821:Genetic Techniques; D016678:Genome; D015894:Genome, Human; D006579:Heterozygote; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018895:Microsatellite Repeats; D009154:Mutation; D013093:Spermatogonia / Q000528:radiation effects*; D014965:X-Rays
D004247:DNA