Department of Animal Sciences, Washington State University, Pullman, WA 99164-7620.
Department of Psychology, Washington State University, Pullman, WA 99164-4820.
Int J Biol Sci. 2021 Jan 1;17(1):119-133. doi: 10.7150/ijbs.51628. eCollection 2021.
Because of their relatively short lifespan (<4 years), rats have become the second most used model organism to study health and diseases in humans who may live for up to 120 years. First-, second- and third-generation sequencing technologies and platforms have produced increasingly greater sequencing depth and accurate reads, leading to significant advancements in the rat genome assembly during the last 20 years. In fact, whole genome sequencing (WGS) of 47 strains have been completed. This has led to the discovery of genome variants in rats, which have been widely used to detect quantitative trait loci underlying complex phenotypes based on gene, haplotype, and sweep association analyses. DNA variants can also reveal strain, chromosome and gene functional evolutions. In parallel, phenome programs have advanced significantly in rats during the last 15 years and more than 10 databases host genome and/or phenome information. In order to discover the bridges between genome and phenome, systems genetics and integrative genomics approaches have been developed. On the other hand, multiple level information transfers from genome to phenome are executed by differential usage of alternative transcriptional start (ATS) and polyadenylation (APA) sites per gene. We used our own experiments to demonstrate how alternative transcriptome analysis can lead to enrichment of phenome-related causal pathways in rats. Development of advanced genome-to-phenome assays will certainly enhance rats as models for human biomedical research.
由于其相对较短的寿命（<4 年），大鼠已成为继人类之后用于研究健康和疾病的第二大模型生物，人类的寿命可能长达 120 年。第一代、第二代和第三代测序技术和平台产生了越来越大的测序深度和准确的读数，导致在过去 20 年中大鼠基因组组装取得了重大进展。事实上，已经完成了 47 个品系的全基因组测序（WGS）。这导致在大鼠中发现了基因组变异，这些变异已被广泛用于基于基因、单倍型和全基因组关联分析检测复杂表型的数量性状位点。DNA 变异还可以揭示品系、染色体和基因的功能进化。与此同时，在过去的 15 年中，大鼠的表型计划也取得了显著进展，超过 10 个数据库拥有基因组和/或表型信息。为了发现基因组和表型之间的桥梁，系统遗传学和综合基因组学方法已经得到了发展。另一方面，通过每个基因的差异使用选择性转录起始（ATS）和多聚腺苷酸化（APA）位点，从基因组到表型进行多层次信息传递。我们使用自己的实验证明了如何通过对选择性转录组进行分析，从而富集大鼠中与表型相关的因果途径。先进的基因组到表型测定法的发展肯定会增强大鼠作为人类生物医学研究模型的地位。
