Hasin-Brumshtein Yehudit, Khan Arshad H, Hormozdiari Farhad, Pan Calvin, Parks Brian W, Petyuk Vladislav A, Piehowski Paul D, Brümmer Anneke, Pellegrini Matteo, Xiao Xinshu, Eskin Eleazar, Smith Richard D, Lusis Aldons J, Smith Desmond J
Department of Human Genetics, University of California, Los Angeles, Los Angeles, United States.
David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States.
Elife. 2016 Sep 13;5:e15614. doi: 10.7554/eLife.15614.
Previous studies had shown that the 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 and expression Quantitative Trait Loci (eQTLs) demonstrating 2 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 provide a rich resource for understanding the many physiologic functions mediated by the hypothalamus and their genetic regulation.
先前的研究表明，将代谢组织中的全基因组表达谱与遗传和表型变异相结合，能为潜在的分子机制提供有价值的见解。我们使用RNA测序来表征来自杂交小鼠多样性面板（HMDP）的99个近交系小鼠的下丘脑转录组，HMDP是心血管和代谢性状的参考资源群体。我们报告了蛋白质组学分析支持的众多新转录本以及新的非编码RNA。HMDP中转录本水平的高分辨率遗传图谱揭示了顺式和反式表达数量性状基因座（eQTL），证明了与数百个基因表达相关的2个eQTL“热点”。我们还报告了数千个受遗传变异调控的可变剪接事件。最后，与约150种代谢和心血管性状的比较揭示了许多高度显著的关联。我们的数据为理解下丘脑介导的多种生理功能及其遗传调控提供了丰富的资源。
