title: Tissue-specific mitochondrial heteroplasmy at position 16,093 within the same individual.
abstract: Human mitochondrial DNA (mtDNA) research has entered a massively parallel sequencing (MPS) era, providing deep insight into mtDNA genomics and molecular diagnostics. Analysis can simultaneously include coding and control regions, many samples can be studied in parallel, and even minor heteroplasmic changes can be detected. We investigated heteroplasmy using 16 different tissues from three unrelated males aged 40-54 years at the time of death. mtDNA was enriched using two independent overlapping long-range PCR amplicons and analysed by employing illumina paired-end sequencing. Point mutation heteroplasmy at position 16,093 (m.16093T > C) in the non-coding regulatory region showed great variability among one of the studied individuals; heteroplasmy extended from 5.1 % in red bone marrow to 62.0 % in the bladder. Red (5.1 %) and yellow bone marrow (8.9 %) clustered into one group and two arteries and two aortas from different locations into another (31.2-50.9 %), giving an ontogenetic explanation for the formation of somatic mitochondrial heteroplasmy. Our results demonstrate that multi-tissue screening using MPS provides surprising data even when there is a limited number (3) of study subjects and they give reason to speculate that mtDNA heteroplasmic frequency, distribution, and even its possible role in complex diseases or phenotypes seem to be underestimated.
authors.affiliation: Competence Centre on Reproductive Medicine and Biology, Tartu, Estonia, kaarel.krjutshkov@gmail.com.
authors.forename: Kaarel
authors.initials: K
authors.lastname: Krjutškov
authors.forename: Marina
authors.initials: M
authors.lastname: Koltšina
authors.forename: Kelli
authors.initials: K
authors.lastname: Grand
authors.forename: Urmo
authors.initials: U
authors.lastname: Võsa
authors.forename: Martin
authors.initials: M
authors.lastname: Sauk
authors.forename: Neeme
authors.initials: N
authors.lastname: Tõnisson
authors.forename: Andres
authors.initials: A
authors.lastname: Salumets
mesh_terms: D000328:Adult; D000483:Alleles; D004272:DNA, Mitochondrial; D054629:Genome, Mitochondrial; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009928:Organ Specificity / Q000235:genetics; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide
chemical_list: D004272:DNA, Mitochondrial