Networking in Biology: The Hybrid Rat Diversity Panel.

Networking in Biology: The Hybrid Rat Diversity Panel.
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DOI:
10.1007/978-1-4939-9581-3_10
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发表时间:
2019
影响因子:
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通讯作者:
B. Tabakoff;Harry Smith;L. Vanderlinden;P. Hoffman;L. Saba
B. Tabakoff;Harry Smith;L. Vanderlinden;P. Hoffman;L. Saba
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文献类型:
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作者:
B. Tabakoff;Harry Smith;L. Vanderlinden;P. Hoffman;L. Saba

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非人类哺乳动物系统遗传学研究最富有成果的资源之一是一组近交系菌株,它们在品系之间表现出显着的遗传多样性,但在品系内表现出遗传稳定性(同源性)。这些特征允许对复杂表型(QTL)进行精细定位,并提供统计能力来识别名义上对表型有贡献的基因座。这种类型的资源还允许在几代实验动物中使用相同的遗传背景来规划和执行调查。通常,在生理学和行为学研究中,大鼠比小鼠更受青睐,因为它们的体型更大,解剖学更具区分性(特别是它们的中枢神经系统)。杂交大鼠多样性小组(HRDP)是一个近交系大鼠品系小组,它结合了两个重组近交系小组(HXB/BXH,30个品系;LEXF/FXLE,34个品系和另外35个近交系大鼠,根据它们的全基因组测序和/或彻底的基因分型,选择了遗传多样性)。这种用于作图研究的面板的遗传多样性和统计能力超过或超过了目前在老鼠身上可用的面板。该面板的遗传稳定性使其特别适合于高通量组学数据的收集,因为相关技术可用于从事真正集成的系统生物学。PhenoGen网站(http://phenogen.org)是初始转录组数据的储存库,使原始数据、处理后的数据和分析结果,如器官特定蛋白编码和非编码转录本、异构体分析、表达数量性状基因座和共表达网络,可供研究公众使用。正在开发的数据集和工具将补充目前分析人类转录组及其遗传控制(基因类型-组织表达项目(GTEx))的努力,并允许解剖易于在人类中研究的特定表型和基因与环境之间的相互作用的遗传网络。HRDP是探索真正整合的系统遗传学的必要群体。
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.