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多样性远交系小鼠纹状体的基因表达遗传学

Gene expression genetics of the striatum of Diversity Outbred mice.

作者信息

Philip Vivek M, He Hao, Saul Michael C, Dickson Price E, Bubier Jason A, Chesler Elissa J

机构信息

The Jackson Laboratory for Mammalian Genetics, Bar Harbor, ME 04605.

The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032.

出版信息

bioRxiv. 2023 May 12:2023.05.11.540390. doi: 10.1101/2023.05.11.540390.

Abstract

Brain transcriptional variation is a heritable trait that mediates complex behaviors, including addiction. Expression quantitative trait locus (eQTL) mapping reveals genomic regions harboring genetic variants that influence transcript abundance. In this study, we profiled transcript abundance in the striatum of 386 Diversity Outbred (J:DO) mice of both sexes using RNA-Seq. All mice were characterized using a behavioral battery of widely-used exploratory and risk-taking assays prior to transcriptional profiling. We performed eQTL mapping, incorporated the results into a browser-based eQTL viewer, and deposited co-expression network members in GeneWeaver. The eQTL viewer allows researchers to query specific genes to obtain allelic effect plots, analyze SNP associations, assess gene expression correlations, and apply mediation analysis to evaluate whether the regulatory variant is acting through the expression of another gene. GeneWeaver allows multi-species comparison of gene sets using statistical and combinatorial tools. This data resource allows users to find genetic variants that regulate differentially expressed transcripts and place them in the context of other studies of striatal gene expression and function in addiction-related behavior.

摘要

大脑转录变异是一种可遗传的性状,它介导包括成瘾在内的复杂行为。表达定量性状位点(eQTL)定位揭示了含有影响转录本丰度的遗传变异的基因组区域。在本研究中,我们使用RNA测序对386只不同性别的多样性远交(J:DO)小鼠纹状体中的转录本丰度进行了分析。在转录分析之前,所有小鼠都使用一系列广泛使用的探索性和冒险性检测行为进行了表征。我们进行了eQTL定位,将结果整合到基于浏览器的eQTL查看器中,并将共表达网络成员存入GeneWeaver。该eQTL查看器允许研究人员查询特定基因以获得等位基因效应图、分析SNP关联、评估基因表达相关性,并应用中介分析来评估调控变异是否通过另一个基因的表达起作用。GeneWeaver允许使用统计和组合工具对基因集进行多物种比较。这个数据资源允许用户找到调节差异表达转录本的遗传变异,并将它们置于纹状体基因表达和成瘾相关行为功能的其他研究背景中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0ba/10197688/7825571bbaa7/nihpp-2023.05.11.540390v1-f0001.jpg

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