Hypothalamic transcriptomes of 99 mouse strains reveal trans eQTL hotspots, splicing QTLs and novel non-coding genes.
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 bothlocalandtransexpression Quantitative Trait Loci (eQTLs) demonstrating 2transeQTL '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.
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.
Yehudit
0000-0001-7528-603X
Y
Hasin-Brumshtein
Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, United States.
Arshad H
AH
Khan
Department of Computer Science, University of California, Los Angeles, Los Angeles, United States.
Farhad
F
Hormozdiari
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.
Calvin
C
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.|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.
Brian W
BW
Parks
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, United States.
Vladislav A
VA
Petyuk
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, United States.
Paul D
PD
Piehowski
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, United States.
Anneke
A
Brümmer
Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.
Matteo
M
Pellegrini
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, United States.
Xinshu
X
Xiao
Department of Computer Science, University of California, Los Angeles, Los Angeles, United States.
Eleazar
E
Eskin
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, United States.
Richard D
RD
Smith
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.
Aldons J
AJ
Lusis
Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, United States.
Desmond J
DJ
Smith
D017398:Alternative Splicing; D000818:Animals; D002318:Cardiovascular Diseases / Q000235:genetics; D002874:Chromosome Mapping; D056726:Genetic Association Studies; D007031:Hypothalamus / Q000502:physiology*; D008659:Metabolic Diseases / Q000235:genetics; D051379:Mice; D020543:Proteome / Q000032:analysis; D040641:Quantitative Trait Loci; D022661:RNA, Untranslated / Q000032:analysis; D017423:Sequence Analysis, RNA; D059467:Transcriptome
D020543:Proteome; D022661:RNA, Untranslated
RNA-Seq; eQTL; evolutionary biology; genomics; high fat diet; hypothalamus; mouse; neuroscience; obesity; trans-eQTL