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.
- Xinshu Xiao
- Yehudit Hasin-Brumshtein
- Arshad H Khan
- Calvin Pan
- Vladislav A Petyuk
- Paul D Piehowski
- Richard D Smith
- Aldons J Lusis
- Desmond J Smith
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: The animal protocol for the study was approved by the Institutional Animal Care and Use Committee (IACUC) at University of California, Los Angeles.
- Joel K Elmquist, University of Texas Southwestern Medical Center, United States
© 2016, Hasin-Brumshtein et al.
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