Mol. Hum. Reprod. Advance Access originally published online on January 26, 2007
Molecular Human Reproduction 2007 13(3):149-154*; doi:10.1093/molehr/gal112
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mtDNA point mutations are present at various levels of heteroplasmy in human oocytes
1 Department of Genetics and Cell Biology 2 Research institute GROW, University of Maastricht, Maastricht, The Netherlands 3 Mitochondrial Research Group, University of Newcastle upon Tyne, Newcastle upon Tyne, UK 4 Department of IVF, Academic Hospital Maastricht, Maastricht, The Netherlands 5 Department of Neurology, Erasmus Medical Center Rotterdam, Rotterdam, Netherlands
6 To whom correspondence should be addressed at: Department of Genetics and Cell Biology, University of Maastricht, P.O. Box 616, 6200 MD Maastricht, The Netherlands. Tel: +31 (0)43 3881995; Fax: +31 (0)43 3884573; E-mail: bert.smeets{at}molcelb.unimaas.nl
Little is known about the load of mutations and polymorphisms in the mitochondrial DNA (mtDNA) of human oocytes and the possible effect these mutations may have during life. To investigate this, we optimised at the single cell level the recently developed method to screen the entire mtDNA for mainly heteroplasmic mutations by denaturing high performance liquid chromatography analysis. This method is sensitive (
1% heteroplasmy detectable), specific and rapid. The entire mtDNA of 26 oocytes of 13 women was screened by this method. Ten different heteroplasmic mutations, of which only one was located in the D-loop and two were observed twice, were detected in seven oocytes with mutation loads ranging from <5% to 50%. From eight women >1 oocyte was received and in four of them heteroplasmic differences between oocytes of the same woman were observed. In one of these four, two homoplasmic D-loop variants were also detected. Additionally, four oocytes of a single woman were sequenced using the MitoChip® (which lacks the D-loop region), but all sequences were identical. It is concluded that heteroplasmic mtDNA mutations are common in oocytes and that, depending on the position and mutation load, they might increase the risk on developing OXPHOS disease early or later in life.
Key words: DHPLC/MitoChip®/Mitochondrial DNA (mtDNA)/oocytes and bottleneck
* N.B. An error was made in the initial online pagination of Molecular Human Reproduction 13/3. The page span of this article was originally shown as 9–14. The publisher wishes to apologise for this error.
Submitted on October 8, 2006; resubmitted on November 24, 2006; accepted on November 30, 2006.
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