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 (US)
Article numberR59
JournalGenome biology
Volume12
Issue number6
DOIs
StatePublished - Jun 23 2011

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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

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title = "Dynamics of mitochondrial heteroplasmy in three families investigated via a repeatable re-sequencing study",
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.",
author = "Hiroki Goto and Benjamin Dickins and Enis Afgan and Paul, {Ian M.} and James Taylor and Makova, {Kateryna D.} and Anton Nekrutenko",
year = "2011",
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doi = "10.1186/gb-2011-12-6-r59",
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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

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T1 - Dynamics of mitochondrial heteroplasmy in three families investigated via a repeatable re-sequencing study

AU - Goto, Hiroki

AU - Dickins, Benjamin

AU - Afgan, Enis

AU - Paul, Ian M.

AU - Taylor, James

AU - Makova, Kateryna D.

AU - Nekrutenko, Anton

PY - 2011/6/23

Y1 - 2011/6/23

N2 - 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.

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