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

Goto, H., Dickins, B. ORCID: 0000-0002-0866-6232, Afgan, E., Paul, I.M., Taylor, J., Makova, K.D. and Nekrutenko, A., 2011. Dynamics of mitochondrial heteroplasmy in three families investigated via a repeatable re-sequencing study. Genome Biology, 12 (6), R59. ISSN 1465-6906

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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.

Item Type:	Journal article
Publication Title:	Genome Biology
Creators:	Goto, H., Dickins, B., Afgan, E., Paul, I.M., Taylor, J., Makova, K.D. and Nekrutenko, A.
Publisher:	BioMed Central Ltd.
Place of Publication:	London
Date:	2011
Volume:	12
Number:	6
ISSN:	1465-6906
Identifiers:	Number Type 10.1186/gb-2011-12-6-r59 DOI
Rights:	© 2011 Goto et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Central Attribution License (http://creativecommons.0rg/licenses/by/2.O), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Divisions:	Schools > School of Science and Technology
Record created by:	EPrints Services
Date Added:	09 Oct 2015 09:45
Last Modified:	09 Jun 2017 13:10
URI:	https://irep.ntu.ac.uk/id/eprint/2377

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