Leow Soon-Sen, Khoo Jia-Shiun, Ng Siuk-Mun, Lee Wei-Kang, Hoh Chee-Choong, Fairus Syed, Sambanthamurthi Ravigadevi, Hayes K C
Malaysian Palm Oil Board, No. 6, Persiaran Institusi, Bandar Baru Bangi, 43000, Kajang, Selangor, Malaysia.
Codon Genomics Sdn Bhd, No. 26, Jalan Dutamas 7, Taman Dutamas Balakong, 43200, Seri Kembangan, Selangor, Malaysia.
Genetica. 2024 Feb;152(1):11-29. doi: 10.1007/s10709-023-00202-z. Epub 2023 Dec 15.
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.
非洲草鼠或尼罗河鼠（NR）（非洲沼鼠）是一种草食性昼行性啮齿动物，被用作2型糖尿病（T2DM）和昼夜节律研究的生物学模型。与人类相似，雄性NRs在高碳水化合物饮食下会患上T2DM。因此，NR提供了一个独特的机会，来识别表征人类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）有助于确定NRs在圈养环境中自发患上T2DM的可能遗传原因。在本研究中，我们使用PacBio高保真长读长测序技术，对从一只雄性NR分离的肝脏脱氧核糖核酸（DNA）样本进行了WGS。然后，利用PacBio HiFi异构体测序（Iso-Seq）数据以及之前的Illumina RNA测序（RNA-Seq）数据，对获得的WGS数据进行从头组装和注释。与胰岛素和昼夜节律途径相关的基因存在于NR基因组中，类似于大鼠、小鼠和人类基因组中的直系同源基因。因此，与其他生物学模型相比，NR中T2DM的发生很可能不归因于这些基因的结构差异。有必要进行进一步研究，以深入了解NRs发生T2DM的遗传易感性背后的遗传环境因素。
