Ershov N I, Markel A L, Redina O E
Federal Research Center, Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090, Russia.
Biochemistry (Mosc). 2017 Feb;82(2):224-235. doi: 10.1134/S0006297917020146.
Single-nucleotide polymorphisms (SNPs) in the coding and regulatory regions of genes can affect transcription rate and translation efficiency, modify protein function, and, in some cases, cause the development of diseases. In the current study, the RNA-Seq approach has been used to discover strain-specific SNPs in ISIAH (inherited stress-induced arterial hypertension) rats, which are known as a model of stress-induced arterial hypertension. The comparison of the ISIAH SNPs with genome sequencing data available for another 42 rat strains and substrains, 11 of them known as hypertensive, showed a considerable genetic distance between the genotypes of ISIAH and all other rat strains and substrains. The study revealed 1849 novel SNPs specific for ISIAH rats and 158 SNPs present only in the genotypes of hypertensive rats. Amino acid substitutions with possible deleterious effect on protein function were detected. Several of them were found in the genes associated with hypertension. These SNPs may be considered as novel molecular targets for further studies aimed at assessing their potential in the therapy of stress-induced hypertension.
基因编码区和调控区的单核苷酸多态性(SNP)可影响转录速率和翻译效率,改变蛋白质功能,在某些情况下还会引发疾病。在本研究中,RNA测序方法被用于在ISIAH(遗传性应激诱导性动脉高血压)大鼠中发现菌株特异性SNP,ISIAH大鼠是应激诱导性动脉高血压的模型。将ISIAH的SNP与另外42个大鼠品系和亚品系的基因组测序数据进行比较,其中11个已知为高血压品系,结果显示ISIAH与所有其他大鼠品系和亚品系的基因型之间存在相当大的遗传距离。该研究发现了1849个ISIAH大鼠特有的新SNP以及仅存在于高血压大鼠基因型中的158个SNP。检测到了对蛋白质功能可能有有害影响的氨基酸替换。其中一些存在于与高血压相关的基因中。这些SNP可被视为进一步研究的新分子靶点,旨在评估它们在应激诱导性高血压治疗中的潜力。