Evidence for mitochondrial genetic control of autosomal gene expression

<span class="paragraphSection"><div class="boxTitle">Abstract</div>The mitochondrial and nuclear genomes coordinate and co-evolve in eukaryotes in order to adapt to environmental changes. Variation in the mitochondrial genome is capable of affecting expression of genes on the nuclear genome. Sex-specific mitochondrial genetic control of gene expression has been demonstrated in <span style="font-style:italic;">Drosophila melanogaster</span>, where males were found to drive most of the total variation in gene expression. This has potential implications for male-related health and disease resulting from variation in mtDNA solely inherited from the mother. We used a family-based study comprised of 47,323 gene expression probes and 78 mitochondrial SNPs (mtSNPs) from <span style="font-style:italic;">n</span> = 846 individuals to examine the extent of mitochondrial genetic control of gene expression in humans. This identified 15 significant probe-mtSNP associations (<span style="font-style:italic;">P</span><10−8) corresponding to 5 unique genes on the mitochondrial and nuclear genomes, with three of these genes corresponding to mitochondrial genetic control of gene expression in the nuclear genome. The associated mtSNPs for three genes (one <span style="font-style:italic;">cis</span> and two <span style="font-style:italic;">trans</span> associations) were replicated (<span style="font-style:italic;">P <</span> 0.05) in an independent dataset of <span style="font-style:italic;">n</span> = 452 unrelated individuals. There was no evidence for sexual dimorphic gene expression in any of these five probes. Sex-specific effects were examined by applying our analysis to males and females separately and testing for differences in effect size. The <span style="font-style:italic;">MEST</span> gene was identified as having the most significantly different effect sizes across the sexes (<span style="font-style:italic;">P</span>≈10−7). <span style="font-style:italic;">MEST</span> was similarly expressed in males and females with the G allele; however, males with the C allele are highly expressed for <span style="font-style:italic;">MEST</span>, while females show no expression of the gene. This study provides evidence for the mitochondrial genetic control of expression of several genes in humans, with little evidence found for sex-specific effects.</span>

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2l7J5ye
via IFTTT