多脑区在近交系杂种大鼠中的调控图谱。
The regulatory landscape of multiple brain regions in outbred heterogeneous stock rats.
机构信息
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Department of Integrative Structural and Computational Biology, Scripps Research, La Jolla, CA, USA.
出版信息
Nucleic Acids Res. 2022 Oct 28;50(19):10882-10895. doi: 10.1093/nar/gkac912.
Heterogeneous Stock (HS) rats are a genetically diverse outbred rat population that is widely used for studying genetics of behavioral and physiological traits. Mapping Quantitative Trait Loci (QTL) associated with transcriptional changes would help to identify mechanisms underlying these traits. We generated genotype and transcriptome data for five brain regions from 88 HS rats. We identified 21 392 cis-QTLs associated with expression and splicing changes across all five brain regions and validated their effects using allele specific expression data. We identified 80 cases where eQTLs were colocalized with genome-wide association study (GWAS) results from nine physiological traits. Comparing our dataset to human data from the Genotype-Tissue Expression (GTEx) project, we found that the HS rat data yields twice as many significant eQTLs as a similarly sized human dataset. We also identified a modest but highly significant correlation between genetic regulatory variation among orthologous genes. Surprisingly, we found less genetic variation in gene regulation in HS rats relative to humans, though we still found eQTLs for the orthologs of many human genes for which eQTLs had not been found. These data are available from the RatGTEx data portal (RatGTEx.org) and will enable new discoveries of the genetic influences of complex traits.
杂种(HS)大鼠是一种遗传多样性的远交大鼠群体,广泛用于研究行为和生理特征的遗传学。绘制与转录变化相关的数量性状基因座(QTL)图谱将有助于确定这些特征的潜在机制。我们从 88 只 HS 大鼠中生成了五个大脑区域的基因型和转录组数据。我们鉴定出了 21392 个与所有五个大脑区域的表达和剪接变化相关的顺式-QTL,并使用等位基因特异性表达数据验证了它们的效应。我们鉴定出了 80 个情况,其中 eQTL 与来自九个生理特征的全基因组关联研究(GWAS)结果共定位。将我们的数据集与来自基因型组织表达(GTEx)项目的人类数据进行比较,我们发现 HS 大鼠数据产生的显著 eQTL 是类似大小的人类数据集的两倍。我们还发现了同源基因之间遗传调控变异之间存在适度但高度显著的相关性。令人惊讶的是,我们发现 HS 大鼠的基因调控遗传变异相对较少,尽管我们仍然发现了许多人类基因的同源基因的 eQTL,而这些基因的 eQTL 尚未被发现。这些数据可从 RatGTEx 数据门户(RatGTEx.org)获得,将能够为复杂特征的遗传影响的新发现提供支持。