Dynamics of mitochondrial heteroplasmy in three families investigated via a repeatable re-sequencing study

Hiroki Goto, Benjamin Dickins, Enis Afgan, Ian M. Paul, James Taylor, Kateryna D. Makova, Anton Nekrutenko

    Research output: Contribution to journalArticle

    74 Citations (Scopus)

    Abstract

    Background: Originally believed to be a rare phenomenon, heteroplasmy - the presence of more than one mitochondrial DNA (mtDNA) variant within a cell, tissue, or individual - is emerging as an important component of eukaryotic genetic diversity. Heteroplasmies can be used as genetic markers in applications ranging from forensics to cancer diagnostics. Yet the frequency of heteroplasmic alleles may vary from generation to generation due to the bottleneck occurring during oogenesis. Therefore, to understand the alterations in allele frequencies at heteroplasmic sites, it is of critical importance to investigate the dynamics of maternal mtDNA transmission.Results: Here we sequenced, at high coverage, mtDNA from blood and buccal tissues of nine individuals from three families with a total of six maternal transmission events. Using simulations and re-sequencing of clonal DNA, we devised a set of criteria for detecting polymorphic sites in heterogeneous genetic samples that is resistant to the noise originating from massively parallel sequencing technologies. Application of these criteria to nine human mtDNA samples revealed four heteroplasmic sites.Conclusions: Our results suggest that the incidence of heteroplasmy may be lower than estimated in some other recent re-sequencing studies, and that mtDNA allelic frequencies differ significantly both between tissues of the same individual and between a mother and her offspring. We designed our study in such a way that the complete analysis described here can be repeated by anyone either at our site or directly on the Amazon Cloud. Our computational pipeline can be easily modified to accommodate other applications, such as viral re-sequencing.

    Original languageEnglish
    Article numberR59
    JournalGenome biology
    Volume12
    Issue number6
    DOIs
    Publication statusPublished - Jun 23 2011

    Fingerprint

    Mitochondrial Dynamics
    Mitochondrial DNA
    mitochondrial DNA
    gene frequency
    Gene Frequency
    allele
    Mothers
    High-Throughput Nucleotide Sequencing
    Oogenesis
    application coverage
    Cheek
    genetic marker
    oogenesis
    DNA Sequence Analysis
    Genetic Markers
    angle of incidence
    Noise
    cancer
    blood
    family

    All Science Journal Classification (ASJC) codes

    • Ecology, Evolution, Behavior and Systematics
    • Genetics
    • Cell Biology

    Cite this

    Goto, H., Dickins, B., Afgan, E., Paul, I. M., Taylor, J., Makova, K. D., & Nekrutenko, A. (2011). Dynamics of mitochondrial heteroplasmy in three families investigated via a repeatable re-sequencing study. Genome biology, 12(6), [R59]. https://doi.org/10.1186/gb-2011-12-6-r59

    Dynamics of mitochondrial heteroplasmy in three families investigated via a repeatable re-sequencing study. / Goto, Hiroki; Dickins, Benjamin; Afgan, Enis; Paul, Ian M.; Taylor, James; Makova, Kateryna D.; Nekrutenko, Anton.

    In: Genome biology, Vol. 12, No. 6, R59, 23.06.2011.

    Research output: Contribution to journalArticle

    Goto, H, Dickins, B, Afgan, E, Paul, IM, Taylor, J, Makova, KD & Nekrutenko, A 2011, 'Dynamics of mitochondrial heteroplasmy in three families investigated via a repeatable re-sequencing study', Genome biology, vol. 12, no. 6, R59. https://doi.org/10.1186/gb-2011-12-6-r59
    Goto, Hiroki ; Dickins, Benjamin ; Afgan, Enis ; Paul, Ian M. ; Taylor, James ; Makova, Kateryna D. ; Nekrutenko, Anton. / Dynamics of mitochondrial heteroplasmy in three families investigated via a repeatable re-sequencing study. In: Genome biology. 2011 ; Vol. 12, No. 6.
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