Soon-Sen Leow, Jia-Shiun Khoo, Siuk-Mun Ng, Wei-Kang Lee, Chee-Choong Hoh, Syed Fairus, Ravigadevi Sambanthamurthi, K. C. Hayes
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引用次数: 0
摘要
非洲草鼠或尼罗河鼠(NR)(Arvicanthis niloticus)是一种草食性昼行啮齿动物,被用作研究 2 型糖尿病(T2DM)和昼夜节律的生物模型。与人类类似,雄性 NR 也会在高碳水化合物饮食中患上 T2DM。因此,NR 提供了一个独特的机会来确定人类 T2DM 的营养和潜在遗传因素,以及潜在抗糖尿病植物化学物质(如水溶性棕榈果提取物)的作用。全基因组测序(WGS)可帮助确定人工饲养的 NR 自发患 T2DM 的可能遗传原因。在本研究中,我们使用 PacBio 高保真长读数测序技术对从雄性 NR 分离出来的肝脏脱氧核糖核酸(DNA)样本进行了 WGS 测序。然后利用 PacBio HiFi 异构体测序(Iso-Seq)数据和之前的 Illumina RNA 测序(RNA-Seq)数据对获得的 WGS 数据进行了全新的组装和注释。NR基因组中存在与胰岛素和昼夜节律通路相关的基因,这与大鼠、小鼠和人类基因组中的同源基因相似。因此,与其他生物模型相比,T2DM 在 NR 中的发生很可能不是由于这些基因的结构差异造成的。为了进一步了解导致 NR 发生 T2DM 的遗传易感性的遗传环境因素,我们有必要开展进一步的研究。
Insulin and circadian rhythm genes of the Nile rat (Arvicanthis niloticus) are conserved and orthologous to those in the rat, mouse and human
The African grass or Nile rat (NR) (Arvicanthis niloticus) is a herbivorous diurnal rodent which is used as a biological model for research on type 2 diabetes mellitus (T2DM) and the circadian rhythm. Similar to humans, male NRs develop T2DM with high-carbohydrate diets. The NR thus provides a unique opportunity to identify the nutritional and underlying genetic factors that characterise human T2DM, as well as the effects of potential anti-diabetic phytochemicals such as Water-Soluble Palm Fruit Extract. Whole genome sequencing (WGS) could help identify possible genetic causes why NRs spontaneously develop T2DM in captivity. In this study, we performed WGS on a hepatic deoxyribonucleic acid (DNA) sample isolated from a male NR using PacBio high-fidelity long-read sequencing. The WGS data obtained were then de novo assembled and annotated using PacBio HiFi isoform sequencing (Iso-Seq) data as well as previous Illumina RNA sequencing (RNA-Seq) data. Genes related to insulin and circadian rhythm pathways were present in the NR genome, similar to orthologues in the rat, mouse and human genomes. T2DM development in the NR is thus most likely not attributable to structural differences in these genes when compared to other biological models. Further studies are warranted to gain additional insights on the genetic-environmental factors which underlie the genetic permissiveness of NRs to develop T2DM.
期刊介绍:
Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance.
Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.