Abstract:
:Mitochondria play important roles in cellular processes and disease, yet little is known about how the transcriptional regime of the mitochondrial genome varies across individuals and tissues. By analyzing >11,000 RNA-sequencing libraries across 36 tissue/cell types, we find considerable variation in mitochondrial-encoded gene expression along the mitochondrial transcriptome, across tissues and between individuals, highlighting the importance of cell-type specific and post-transcriptional processes in shaping mitochondrial-encoded RNA levels. Using whole-genome genetic data we identify 64 nuclear loci associated with expression levels of 14 genes encoded in the mitochondrial genome, including missense variants within genes involved in mitochondrial function (TBRG4, MTPAP and LONP1), implicating genetic mechanisms that act in trans across the two genomes. We replicate ~21% of associations with independent tissue-matched datasets and find genetic variants linked to these nuclear loci that are associated with cardio-metabolic phenotypes and Vitiligo, supporting a potential role for variable mitochondrial-encoded gene expression in complex disease.
journal_name
Elifejournal_title
eLifeauthors
Ali AT,Boehme L,Carbajosa G,Seitan VC,Small KS,Hodgkinson Adoi
10.7554/eLife.41927subject
Has Abstractpub_date
2019-02-18 00:00:00issn
2050-084Xpii
41927journal_volume
8pub_type
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