Data from: Hypothalamic transcriptomes of 99 mouse strains reveal trans eQTL hotspots, splicing QTLs and novel non-coding genes

Previous studies had shown that integration of genome wide expression profiles, in metabolic tissues, with genetic and phenotypic variance, provided valuable insight into the underlying molecular mechanisms. We used RNA-Seq to characterize hypothalamic transcriptome in 99 inbred strains of mice from the Hybrid Mouse Diversity Panel (HMDP), a reference resource population for cardiovascular and metabolic traits. We report numerous novel transcripts supported by proteomic analyses, as well as novel non coding RNAs. High resolution genetic mapping of transcript levels in HMDP, reveals both local and trans expression Quantitative Trait Loci (eQTLs) demonstrating 2 trans eQTL 'hotspots' associated with expression of hundreds of genes. We also report thousands of alternative splicing events regulated by genetic variants. Finally, comparison with about 150 metabolic and cardiovascular traits revealed many highly significant associations. Our data provides a rich resource for understanding the many physiologic functions mediated by the hypothalamus and their genetic regulation.既往研究表明，将代谢组织的全基因组表达谱与遗传和表型变异相结合，可为解析潜在分子机制提供重要见解。本研究利用RNA测序（RNA-Seq），对来自杂交小鼠多样性面板（Hybrid Mouse Diversity Panel, HMDP）的99个近交系小鼠的下丘脑转录组进行表征；HMDP是心血管与代谢性状的参考资源群体。本研究报道了经蛋白质组学分析验证的大量新型转录本，以及新型非编码RNA。对HMDP群体中转录本水平开展高分辨率遗传定位，共鉴定到顺式（local）和反式（trans）表达数量性状位点（expression Quantitative Trait Loci, eQTLs），其中存在2个与数百个基因表达相关的反式eQTL热点。本研究还报道了数千个受遗传变异调控的可变剪接事件。最后，通过与约150项代谢及心血管性状进行关联分析，本研究发现了诸多高度显著的关联结果。本研究数据为解析下丘脑介导的多种生理功能及其遗传调控机制提供了丰富的研究资源。