Fine mapping of radiation susceptibility and gene expression analysis of LEC congenic rat lines

• Published in: Genomics (San Diego, Calif.) Calif.), 2005-09, Vol.86 (3), p.271-279
• Main Authors: Tsuji, Atsushi B., Sugyo, Aya, Ogiu, Toshiaki, Sagara, Masashi, Kimura, Tomo, Ishikawa, Atsuko, Sudo, Hitomi, Ohtsuki, Marika, Aburatani, Hiroyuki, Imai, Takashi, Harada, Yoshi-nobu
• Format: Article
• Language: English
• Subjects: Animals; Animals, congenic; Animals, Congenic - genetics; Biological and medical sciences; Chromosome Mapping; Classical genetics, quantitative genetics, hybrids; Fundamental and applied biological sciences. Psychology; Gene Expression; Genes. Genome; Genetics of eukaryotes. Biological and molecular evolution; Methods, theories and miscellaneous; Molecular and cellular biology; Molecular genetics; Radiation Tolerance - genetics; Radiation, ionizing; Rats; Rats, inbred LEC; Rats, Inbred LEC - genetics; Whole-body irradiation; X-Rays
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1016/j.ygeno.2005.05.007

LEC rats constitute an animal model of high susceptibility to X-rays. We developed congenic LEC rat lines (recipient strain, Fischer 344 (F344)) and performed genome-wide genotyping to identify radiation susceptibility genes. We mapped seven positional candidate genes, Bmp10, Gpr73, Gp9, Cnbp, Copg, Rab7, and Rpn1, to an ∼1.2-Mb region located between loci D4Got85 and D4Got148 on chromosome 4. None of the seven genes has been reported to be associated with radiation susceptibility. Comparison of the coding sequences for these seven genes in F344 and LEC rats showed no changes in deduced amino acid sequences. We determined gene expression differences in Gp73, Gp9, and Cnbp as well as strain-specific variations in upstream sequences of these genes. Our results suggest that radiation susceptibility in the LEC rat is primarily attributable to one of the genes within this ∼1.2-Mb region; however, expression analysis gave no clear indication as to which gene is responsible.