Journal
GENOME RESEARCH
Volume 25, Issue 11, Pages 1610-1621Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gr.193342.115
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Funding
- Child Health Research Institute
- Lucile Packard Foundation for Children's Health
- Stanford CTSA [UL1TR000093]
- Benchmark Stanford Graduate Fellowship
- Stanford Transformative and Innovation grant
- National Institutes of Health
- National Human Genome Research Institute [NIH/NHGRI T32 HG000044]
- Genentech Graduate Fellowship
- NIH [GM07305907, 1U01HG00761101, HG007611, HG006996]
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Elucidating the consequences of genetic differences between humans is essential for understanding phenotypic diversity and personalized medicine. Although variation in RNA levels, transcription factor binding, and chromatin have been explored, little is known about global variation in translation and its genetic determinants. We used ribosome profiling, RNA sequencing, and mass spectrometry to perform an integrated analysis in lymphoblastoid cell lines from a diverse group of individuals. We find significant differences in RNA, translation, and protein levels suggesting diverse mechanisms of personalized gene expression control. Combined analysis of RNA expression and ribosome occupancy improves the identification of individual protein level differences. Finally, we identify genetic differences that specifically modulate ribosome occupancy-many of these differences lie close to start codons and upstream ORFs. Our results reveal a new level of gene expression variation among humans and indicate that genetic variants can cause changes in protein levels through effects on translation.
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