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; Department of Microbiology, University of California, Los Angeles, Los Angeles, United states; Department of Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States
Arshad H Khan
Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, United States
Farhad Hormozdiari
Department of Computer Science, University of California, Los Angeles, Los Angeles, United States
Calvin Pan
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
Brian W Parks
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; Department of Microbiology, University of California, Los Angeles, Los Angeles, United states; Department of Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States
Vladislav A Petyuk
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, United States
Paul D Piehowski
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, United States
Anneke Brümmer
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, United States
Matteo Pellegrini
Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, United States
Xinshu Xiao
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, United States
Eleazar Eskin
Department of Computer Science, University of California, Los Angeles, Los Angeles, United States
Richard D Smith
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, United States
Aldons J Lusis
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; Department of Microbiology, University of California, Los Angeles, Los Angeles, United states; Department of Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States
Desmond J Smith
Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, United States
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 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 provide a rich resource for understanding the many physiologic functions mediated by the hypothalamus and their genetic regulation.
