Mitochondrial DNA heteroplasmy in the emerging field of massively parallel sequencing

Just, Rebecca S.; Irwin, Jodi A.; Parson, Walther

doi:10.1016/j.fsigen.2015.05.003

Cited by 125 publications

(108 citation statements)

References 81 publications

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“…The lower VF of the additional "discordant" PHPs indicates they were below the range of detection with STS, but detectable with NGS. The reproducibility of the PHPs and the fact they are consistent with reported patterns for coding region PHPs [37] further support the authenticity of these low level variants.…”

Section: Phpssupporting

confidence: 77%

Concordance and reproducibility of a next generation mtGenome sequencing method for high-quality samples using the Illumina MiSeq

Peck

Brandhagen

Marshall

et al. 2016

Forensic Science International: Genetics

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Section: Phpssupporting

confidence: 77%

Concordance and reproducibility of a next generation mtGenome sequencing method for high-quality samples using the Illumina MiSeq

Peck

Brandhagen

Marshall

et al. 2016

Forensic Science International: Genetics

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“…region is a mutational hotspot. This high rate of synonymous MT-ND5 variants are not totally a surprise given the high rate of heteroplasmic alleles in MT-ND5 also found in blood samples (Just et al, 2015) and in oncocytic tumors (Gasparre et al, 2007(Gasparre et al, , 2013.…”

Section: Not Equal Very Strongmentioning

confidence: 70%

Intra-individual purifying selection on mitochondrial DNA variants during human oogenesis

Vicario

Lang

et al. 2017

Human Reproduction

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STUDY QUESTION: Does selection for mtDNA mutations occur in human oocytes?SUMMARY ANSWER: We provide statistical evidence in favor of the existence of purifying selection for mtDNA mutations in human oocytes acting between the expulsion of the first and second polar bodies (PBs).WHAT IS KNOWN ALREADY: Several lines of evidence in Metazoa, including humans, indicate that variation within the germline of mitochondrial genomes is under purifying selection. The presence of this internal selection filter in the germline has important consequences for the evolutionary trajectory of mtDNA. However, the nature and localization of this internal filter are still unclear while several hypotheses are proposed in the literature.STUDY DESIGN, SIZE, DURATION: In this study, 60 mitochondrial genomes were sequenced from 17 sets of oocytes, first and second PBs, and peripheral blood taken from nine women between 38 and 43 years of age.PARTICIPANTS/MATERIALS, SETTING, METHODS: Whole genome amplification was performed only on the single cell samples and Sanger sequencing was performed on amplicons. The comparison of variant profiles between first and second PB sequences showed no difference in substitution rates but displayed instead a sharp difference in pathogenicity scores of protein-coding sequences using three different metrics (MutPred, Polyphen and SNPs&GO).MAIN RESULTS AND THE ROLE OF CHANCE: Unlike the first, second PBs showed no significant differences in pathogenic scores with blood and oocyte sequences. This suggests that a filtering mechanism for disadvantageous variants operates during oocyte development between the expulsion of the first and second PB. LIMITATIONS, REASONS FOR CAUTION:The sample size is small and further studies are needed before this approach can be used in clinical practice. Studies on a model organism would allow the sample size to be increased.

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“…are much less balanced ( Figure 1B) and the lower A signal was not detected by two participants (Table 3 (Table 3), which is understandable [21,22].…”

Section: Tablementioning

confidence: 88%

A collaborative EDNAP exercise on SNaPshot™-based mtDNA control region typing

Weiler

Baca²,

Ballard

et al. 2017

Forensic Science International: Genetics

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A collaborative European DNA Profiling (EDNAP) Group exercise was undertaken to assess the performance of an earlier described SNaPshot™-based screening assay (denoted minimtSNaPshot) [1] that targets 18 single nucleotide polymorphism (SNP) positions in the mitochondrial (mt) DNA control region and allows for discrimination of major European mtDNA haplogroups. Besides the organising laboratory, 14 forensic genetics laboratories were involved in the analysis of 13 samples, which were centrally prepared and thoroughly tested prior to shipment. The samples had a variable complexity and comprised straightforward single-source samples, samples with dropout or altered peak sizing, a point heteroplasmy and twocomponent mixtures resulting in one to five bi-allelic calls. The overall success rate in obtaining useful results was high (97.6%) given that some of the participating laboratories had no previous experience with the typing technology and/or mtDNA analysis. The majority of the participants proceeded to haplotype inference to assess the feasibility of assigning a haplogroup and checking phylogenetic consistency when only 18 SNPs are typed. To mimic casework procedures, the participants compared the SNP typing data of all 13 samples to a set of eight mtDNA reference profiles that were described according to standard nomenclature [2], and indicated whether these references matched each sample or not. Incorrect scorings were obtained for 2% of the comparisons and derived from a subset of the participants, indicating a need for training and guidelines regarding mini-mtSNaPshot data interpretation.

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Mitochondrial DNA heteroplasmy in the emerging field of massively parallel sequencing

Abstract: HighlightsWe provide an update on developments in mtDNA forensic genetics.We review the recent literature for the detection of heteroplasmy using next generation sequencing techniques.We highlight artefacts and problems in datasets.We discuss the implications for forensic practice.

Cited by 125 publications

References 81 publications

Concordance and reproducibility of a next generation mtGenome sequencing method for high-quality samples using the Illumina MiSeq

Concordance and reproducibility of a next generation mtGenome sequencing method for high-quality samples using the Illumina MiSeq

Intra-individual purifying selection on mitochondrial DNA variants during human oogenesis

A collaborative EDNAP exercise on SNaPshot™-based mtDNA control region typing

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