Heteroplasmy
From ISOGG Wiki
Heteroplasmy is the co-existence of multiple mitochondrial DNA variants in a single source. There are multiple copies of mtDNA in each cell. Heteroplasmy is the name given to denote mutations which affect only a proportion of the molecules in a cell. The term homoplasmy is used to describe mutations which affect all of the molecules.
The level of heteroplasmy can vary between cells in the same tissue or organ, from organ to organ within the same person, and between individuals in the same family. Low levels of heteroplasmy have been found in almost every healthy individual who has been studied to date. MtDNA mutations that have occurred within approximately three human generations are usually heteroplasmic. Animal research has suggested that de novo heteroplasmic mutations become fixed and homoplasmic within two or three generations.[1]
If you have taken a mitochondrial DNA test you will know that you have a heteroplasmy from the letter codes used to describe the positions in your mtDNA sequence. Non-heteroplasmic positions are followed by the letters A, C, T or G (the letters which denote the base pairs). Heteroplasmic positions will carry one of the following letters: U, M, R, W, H, D or N. The letter code used determines the nature of the heteroplasmy.[2]
Length heteroplasmy vs. sequence heteroplasmy
Sequence heteroplasmy involves the coexistence of two strains of DNA that differ at a single nucleotide or SNP. For example:
| Strain 1: |
...AGTCTGGATTC... |
| Strain 2: |
...AGTCTAGATTC... |
Length heteroplasmy involves the coexistence of two strains of DNA that have different lengths for tracts of repeated nucleotides. For example:
| Strain 1: |
...TGAATCCCCCCCCCTTGAA... |
| Strain 2: |
...TGAATCCCCCCCCCCCTTGAA... |
Notable cases
A notable example of heteroplasmy was seen in the case of Nicholas II of Russia. His heteroplasmy, and that of his brother, served to convince Russian authorities of the authenticity of his remains.[3],[4]
FTDNA Help Center articles
FTDNA Learning Center articles (archived)
- How is mtDNA heteroplasmy inherited?
- What percentage or amount of mitochondrial DNA (mtDNA) heteroplasmy is needed in order to be detected and reported by Family Tree DNA?
- Is my mitochondrial DNA (mtDNA) mutation medical? How about mitochondrial heteroplasmy? Is it medical?
Further reading
- Turner A. "Now You See It, Now You Don't: Heteroplasmy in Mitochondrial DNA". Satiable Curiosity column. Journal of Genetic Genealogy 2006 2(1): iv-v.
- Davis K. Researchers examine disease-causing mutations in mitochondrial genomes. National Human Genome Research Institute Newsroom, 29 August 2014.
- Russell JD. The Myth of the GD0. The Legal Genealogist, 26 November 2017. A family case study of heteroplasmy.
- Bettinger B. Heteroplasmies and poly-cytosine stretches – an mtDNA case study. The Genetic Genealogist, 21 April 2018.
- Heteroplasmy and mutations An explanation of heteroplasmy from an online course run by the US National Forensic Science Technology Center (from the Internet Archive)
- An international study on the detection of heteroplasmy in mitochondrial DNA. A document brief supplied by Promega Corp with a very clear explanation of heteroplasmy.
- What is HETEROPLASMY? What does HETEROPLASMY mean? HETEROPLASMY meaning, definition & explanation
Scientific papers
- Bolze A, Mendez F, White S et al (2020). A catalog of homoplasmic and heteroplasmic mitochondrial DNA variants in humans (preprint). BioRxiv 798264.
- Wei W, Tuna S, Keogh MJ (2019). Germline selection shapes human mitochondrial DNA diversity. Science 364 (6442): eaau6520 (24 May 2019).
- Morris J, Na Y-J, Zhu H et al (2017). Pervasive within-mitochondrion single-nucleotide variant heteroplasmy as revealed by single-mitochondrion sequencing. Cell Reports 21, 2706–2713.
- A summary of the research can be found here
- Stewart JB, Chinnery PF (2015). The dynamics of mitochondrial DNA heteroplasmy: implications for human health and disease (£). Nature Reviews Genetics 535: 530-542.
- Naue J, Hörer S, Sänger T et al (2015). Evidence for frequent and tissue-specific sequence heteroplasmy in human mitochondrial DNA. Mitochondrion 2015: 20,: 82-94.
- Ye K, Lu J, M F, Keinan A, Gu A (2014). Extensive pathogenicity of mitochondrial heteroplasmy in healthy human individuals. Proceedings of the National Academy of the United States of America 111 (29): 10654-10659.
- Ramos A, Santos C, Mateiu L, Gonzalez MdM, Alvarez L, et al (2013). Frequency and pattern of heteroplasmy in the complete human mitochondrial genome. PLoS ONE 8(10): e74636. doi:10.1371/journal.pone.0074636.
- Payne BAI, Wilson IJ, Yu-Wai-Man P et al (2013). Universal heteroplasmy of human mitochondrial DNA. Human Molecular Genetics 22(2): 384–390.
- Goto H, Dickins B, Afgan E (2011). Dynamics of mitochondrial heteroplasmy in three families investigated via a repeatable re-sequencing study. Genome Biology 12: R59.
- Yiping H et al. Heteroplasmic mitochondrial DNA mutations in normal and tumor cells. Nature Mar 25, 2010; 464(7288): 610–614.
- Melton T. Mitochondrial DNA heteroplasmy. Forensic Science Review 2004: 16: 1.
Blog posts
- Bettinger B. Heteroplasmies and Poly-Cytosine Stretches – An mtDNA Case Study. The Genetic Genealogist 21 April 2018.
- Russell JG. The myth of the GD0. The Legal Genealogist, 26 November 2017.
Tools
References
- ↑ Stewart JB, Chinnery PF (2015). The dynamics of mitochondrial DNA heteroplasmy: implications for human health and disease (£). Nature Reviews Genetics 535: 530-542.
- ↑ How do I know if I have a mitchondrial DNA heteroplasmy? What is the nomenclature?
- ↑ Ivanov PL, Wadhams MJ, Roby RK, Holland MM, Weedn VW, Parsons TJ. Mitochondrial DNA sequence heteroplasmy in the Grand Duke of Russia Georgij Romanov establishes the authenticity of the remains of Tsar Nicholas II. Nat. Genet. April 1996, Volume 12, Issue 4. pp417–20 7
- ↑ Michael D. Coble, Odile M. Loreille, Mark J. Wadhams et al. Mystery Solved: The Identification of the Two Missing Romanov Children Using DNA Analysis. PLoS One' 2009 Volume 4, number 3, p34838.