The pseudo-mitochondrial genome influences mistakes in heteroplasmy interpretation
Ryan Parr,Jennifer Maki,Brian Reguly,Gabriel D. Dakubo,Andrea Aguirre,Roy Wittock,Kerry Robinson,John P. Jakupciak,Robert Thayer +8 more
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TLDR
These findings suggest that mitochondrial genome disease-associated biomarkers must be rigorously authenticated to preclude any affiliation with paralogous nuclear pseudogenes, and are the first to fully sequence 46 paralogyous nuclear DNA fragments that represent the entire mitochondrial genome.Abstract:
Nuclear mitochondrial pseudogenes (numts) are a potential source of contamination during mitochondrial DNA PCR amplification. This possibility warrants careful experimental design and cautious interpretation of heteroplasmic results. Here we report the cloning and sequencing of numts loci, amplified from human tissue and rho-zero (ρ0) cells (control) with primers known to amplify the mitochondrial genome. This paper is the first to fully sequence 46 paralogous nuclear DNA fragments that represent the entire mitochondrial genome. This is a surprisingly small number due primarily to the primer sets used in this study, because prior to this, BLAST searches have suggested that nuclear DNA harbors between 400 to 1,500 paralogous mitochondrial DNA fragments. Our results indicate that multiple numts were amplified simultaneously with the mitochondrial genome and increased the load of pseudogene signal in PCR reactions. Further, the entire mitochondrial genome was represented by multiple copies of paralogous nuclear sequences. These findings suggest that mitochondrial genome disease-associated biomarkers must be rigorously authenticated to preclude any affiliation with paralogous nuclear pseudogenes. Importantly, the common perception that mitochondrial template "swamps" numts loci precluding detectable amplification, depends on the region of the mitochondrial genome targeted by the PCR reaction and the number of pseudogene loci that may co-amplify. Cloning and relevant sequencing data will facilitate the correct interpretation. This is the first complete, wet-lab characterization of numts that represent the entire mitochondrial genome.read more
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Human mitochondrial DNA: roles of inherited and somatic mutations
TL;DR: Insight into the roles of mtDNA mutations in a wide variety of diseases is discussed, highlighting the interesting genetic characteristics of the mitochondrial genome and challenges in studying its contribution to pathogenesis.
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Is mitochondrial DNA content a potential biomarker of mitochondrial dysfunction
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Detecting heteroplasmy from high-throughput sequencing of complete human mitochondrial DNA genomes.
TL;DR: This work used simulations and phiX174 sequence data to design criteria for accurate detection of heteroplasmy with the Illumina Genome Analyzer platform and applied them to mtDNA sequence reads for 131 individuals from five Eurasian populations that had been generated via a parallel tagged approach.
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Revealing the hidden complexities of mtDNA inheritance
TL;DR: It is shown how it is possible to account for recombination and heteroplasmy in evolutionary and population analyses, but that accurate estimates of the frequencies of biparental inheritance and recombination are needed.
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Five Ovine Mitochondrial Lineages Identified From Sheep Breeds of the Near East
Jennifer R. S. Meadows,Jennifer R. S. Meadows,Ibrahim Cemal,Orhan Karaca,Elisha Gootwine,James Kijas +5 more
TL;DR: The identification in this study of evidence for additional domestication events adds to the emerging view that sheep were recruited from wild populations multiple times in the same way as for other livestock species such as goat, cattle, and pig.
References
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TL;DR: All these mitochondrial DMAs stem from one woman who is postulated to have lived about 200,000 years ago, probably in Africa, implying that each area was colonised repeatedly.
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Michael P. King,Giuseppe Attardi +1 more
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