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

研究成果: Contribution to journalArticle査読

78 被引用数 (Scopus)

抄録

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.

本文言語英語
論文番号R59
ジャーナルGenome biology
12
6
DOI
出版ステータス出版済み - 6 23 2011
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生態、進化、行動および分類学
  • 遺伝学
  • 細胞生物学

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