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生物学中的网络:杂交大鼠多样性面板

Networking in Biology: The Hybrid Rat Diversity Panel.

作者信息

Tabakoff Boris, Smith Harry, Vanderlinden Lauren A, Hoffman Paula L, Saba Laura M

机构信息

Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA.

Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado, Aurora, CO, USA.

出版信息

Methods Mol Biol. 2019;2018:213-231. doi: 10.1007/978-1-4939-9581-3_10.

Abstract

One of the most fruitful resources for systems genetic studies of nonhuman mammals is a panel of inbred strains that exhibits significant genetic diversity between strains but genetic stability (isogenicity) within strains. These characteristics allow for fine mapping of complex phenotypes (QTLs) and provide statistical power to identify loci which contribute nominally to the phenotype. This type of resource also allows the planning and performance of investigations using the same genetic backgrounds over several generations of the test animals. Often, rats are preferred over mice for physiologic and behavioral studies because of their larger size and more distinguishable anatomy (particularly for their central nervous system). The Hybrid Rat Diversity Panel (HRDP) is a panel of inbred rat strains, which combines two recombinant inbred panels (the HXB/BXH, 30 strains; the LEXF/FXLE, 34 strains and 35 more strains of inbred rats which were selected for genetic diversity, based on their fully sequenced genomes and/or thorough genotyping). The genetic diversity and statistical power of this panel for mapping studies rivals or surpasses currently available panels in mouse. The genetic stability of this panel makes it particularly suitable for collection of high-throughput omics data as relevant technology becomes available for engaging in truly integrative systems biology. The PhenoGen website ( http://phenogen.org ) is the repository for the initial transcriptome data, making the raw data, the processed data, and the analysis results, e.g., organ-specific protein coding and noncoding transcripts, isoform analysis, expression quantitative trait loci, and co-expression networks, available to the research public. The data sets and tools being developed will complement current efforts to analyze the human transcriptome and its genetic controls (the Genotype-Tissue Expression Project (GTEx)) and allow for dissection of genetic networks that predispose to particular phenotypes and gene-by-environment interactions that are difficult or even impossible to study in humans. The HRDP is an essential population for exploring truly integrative systems genetics.

摘要

对于非人类哺乳动物的系统遗传学研究而言,最富有成效的资源之一是一组近交系,这些近交系在品系间表现出显著的遗传多样性,但在品系内具有遗传稳定性(同基因性)。这些特性有助于对复杂表型(数量性状基因座)进行精细定位,并为识别对表型有显著贡献的基因座提供统计学效力。这种资源类型还允许在几代实验动物中使用相同的遗传背景来规划和开展研究。由于大鼠体型较大且解剖结构更易于区分(特别是其中枢神经系统),在生理和行为研究中,大鼠通常比小鼠更受青睐。杂交大鼠多样性面板(HRDP)是一组近交大鼠品系,它结合了两个重组近交系面板(HXB/BXH,30个品系;LEXF/FXLE,34个品系以及另外35个基于全基因组测序和/或全面基因分型而选择的具有遗传多样性的近交大鼠品系)。该面板在图谱研究中的遗传多样性和统计学效力可与目前小鼠中可用的面板相媲美甚至超越。随着相关技术可用于开展真正的整合系统生物学研究,该面板的遗传稳定性使其特别适合用于高通量组学数据的收集。PhenoGen网站(http://phenogen.org)是初始转录组数据的储存库,向科研公众提供原始数据、处理后的数据以及分析结果,例如器官特异性蛋白质编码和非编码转录本、异构体分析、表达数量性状基因座以及共表达网络。正在开发的数据集和工具将补充当前分析人类转录组及其遗传控制的工作(基因型-组织表达项目(GTEx)),并有助于剖析导致特定表型的遗传网络以及在人类中难以甚至无法研究的基因-环境相互作用。HRDP是探索真正的整合系统遗传学的重要群体。

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