1A.05: COMPARISON OF THE WHOLE GENOME SEQUENCE REVEALED GENETICALLY DISTINCT LOCI BETWEEN SHR/IZM AND SHRSP/IZM. (June 2015) - Isomura, M.
Abstract : Objective: SHR and SHRSP are well-established model rats for studying not only hypertension and/or stoke but also several other adult-onset diseases. These two strains have a significant difference in the stroke susceptibility, which is resulted from the genetic difference. However, difference in the genomic architecture has not been elucidated enough between them. In this study, we therefore performed the comparison of the whole genome sequence of SHR/Izm and SHRSP/Izm, in addition to their control strain, WKY/Izm. Design and method: Genomic DNA of each strain was extracted from the liver. Libraries were prepared from genomic DNA using the EZ Bead system. Sequencing was performed on the SOLiD 4 system. Both paired-end and fragment analyses were performed and read 85 and 50 bases/run, respectively. Five million reads were obtained for the genome of each strain, which covered approximately 20 times of the rat genome. The sequence reads were mapped to the Rattus norvegicus genome assembly (rn6) with the bowtie software. SNPs (Single Nucleotide Polymorphisms) against the rn6 genome sequence were called using SAMtools software. Results: The analysis identified 684, 759 and 999, 114 SNPs in SHR/Izm and SHRSP/Izm, respectively, when the rn6 was used as a reference, SHRSP and SHR shared approximately 64.1% or 63.2% of SNPs with those observed in WKY, respectively. To identify fragments showing obvious difference in the genomic architecture between SHR and SHRSP, the number of SNPs shared with WKY in every 1 kbp bin were compared throughout the genome of SHR or SHRSP. We identified several genomic regions where the number of the shared SNPs were statistically different between SHR and SHRSP. Those loci in SHR and SHRSP were considered to carry a distinct genomic architecture, and might contribute to the phenotypical difference between the two strains. Functional classification of SNPs identified 21 and 18 strain-specific nonsense mutations in the whole genome of SHR and SHRSP, respectively. Conclusions: These results would contribute to identify genomic loci which are responsible for phonotypical differences between SHR and SHRSP.