Next-generation Sequencing of Human Mitochondrial Reference Genomes Uncovers High Heteroplasmy Frequency

Overview

Journal PLoS Comput Biol

Specialty Biology

Date 2012 Nov 8

PMID 23133345

Citations 34

Authors

Maria Ximena Sosa

I K Ashok Sivakumar

Samantha Maragh

Vamsi Veeramachaneni

Ramesh Hariharan

Minothi Parulekar

Karin M Fredrikson

Timothy T Harkins

Jeffrey Lin

Andrew B Feldman

Pramila Tata

Georg B Ehret

Aravinda Chakravarti

Affiliations

Soon will be listed here.

Abstract

We describe methods for rapid sequencing of the entire human mitochondrial genome (mtgenome), which involve long-range PCR for specific amplification of the mtgenome, pyrosequencing, quantitative mapping of sequence reads to identify sequence variants and heteroplasmy, as well as de novo sequence assembly. These methods have been used to study 40 publicly available HapMap samples of European (CEU) and African (YRI) ancestry to demonstrate a sequencing error rate <5.63×10(-4), nucleotide diversity of 1.6×10(-3) for CEU and 3.7×10(-3) for YRI, patterns of sequence variation consistent with earlier studies, but a higher rate of heteroplasmy varying between 10% and 50%. These results demonstrate that next-generation sequencing technologies allow interrogation of the mitochondrial genome in greater depth than previously possible which may be of value in biology and medicine.

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References

White D, Wolff J, Pierson M, Gemmell N . Revealing the hidden complexities of mtDNA inheritance. Mol Ecol. 2009; 17(23):4925-42. DOI: 10.1111/j.1365-294X.2008.03982.x. View

Anderson S, Bankier A, Barrell B, de Bruijn M, Coulson A, Drouin J . Sequence and organization of the human mitochondrial genome. Nature. 1981; 290(5806):457-65. DOI: 10.1038/290457a0. View

Upholt W, Dawid I . Mapping of mitochondrial DNA of individual sheep and goats: rapid evolution in the D loop region. Cell. 1977; 11(3):571-83. DOI: 10.1016/0092-8674(77)90075-7. View

Kadowaki T, Kadowaki H, Mori Y, Tobe K, Sakuta R, Suzuki Y . A subtype of diabetes mellitus associated with a mutation of mitochondrial DNA. N Engl J Med. 1994; 330(14):962-8. DOI: 10.1056/NEJM199404073301403. View

Olivo P, Van de Walle M, Laipis P, Hauswirth W . Nucleotide sequence evidence for rapid genotypic shifts in the bovine mitochondrial DNA D-loop. Nature. 1983; 306(5941):400-2. DOI: 10.1038/306400a0. View

Sam L, Lipson D, Raz T, Cao X, Thompson J, Milos P . A comparison of single molecule and amplification based sequencing of cancer transcriptomes. PLoS One. 2011; 6(3):e17305. PMC: 3046973. DOI: 10.1371/journal.pone.0017305. View

Wallace D, Zheng X, Lott M, Shoffner J, Hodge J, Kelley R . Familial mitochondrial encephalomyopathy (MERRF): genetic, pathophysiological, and biochemical characterization of a mitochondrial DNA disease. Cell. 1988; 55(4):601-10. DOI: 10.1016/0092-8674(88)90218-8. View

Aquadro C, Greenberg B . Human mitochondrial DNA variation and evolution: analysis of nucleotide sequences from seven individuals. Genetics. 1983; 103(2):287-312. PMC: 1219980. DOI: 10.1093/genetics/103.2.287. View

Huse S, Huber J, Morrison H, Sogin M, Welch D . Accuracy and quality of massively parallel DNA pyrosequencing. Genome Biol. 2007; 8(7):R143. PMC: 2323236. DOI: 10.1186/gb-2007-8-7-r143. View

10.

Pereira L, Freitas F, Fernandes V, Pereira J, Costa M, Costa S . The diversity present in 5140 human mitochondrial genomes. Am J Hum Genet. 2009; 84(5):628-40. PMC: 2681004. DOI: 10.1016/j.ajhg.2009.04.013. View

11.

Wallace D . A mitochondrial paradigm for degenerative diseases and ageing. Novartis Found Symp. 2001; 235:247-63; discussion 263-6. DOI: 10.1002/0470868694.ch20. View

12.

Newman N, Lott M, Wallace D . The clinical characteristics of pedigrees of Leber's hereditary optic neuropathy with the 11778 mutation. Am J Ophthalmol. 1991; 111(6):750-62. DOI: 10.1016/s0002-9394(14)76784-4. View

13.

Hartmann A, Thieme M, Nanduri L, Stempfl T, Moehle C, Kivisild T . Validation of microarray-based resequencing of 93 worldwide mitochondrial genomes. Hum Mutat. 2008; 30(1):115-22. DOI: 10.1002/humu.20816. View

14.

. The International HapMap Project. Nature. 2003; 426(6968):789-96. DOI: 10.1038/nature02168. View

15.

Maitra A, Cohen Y, Gillespie S, Mambo E, Fukushima N, Hoque M . The Human MitoChip: a high-throughput sequencing microarray for mitochondrial mutation detection. Genome Res. 2004; 14(5):812-9. PMC: 479107. DOI: 10.1101/gr.2228504. View

16.

Gherman A, Chen P, Teslovich T, Stankiewicz P, Withers M, Kashuk C . Population bottlenecks as a potential major shaping force of human genome architecture. PLoS Genet. 2007; 3(7):e119. PMC: 1925129. DOI: 10.1371/journal.pgen.0030119. View

17.

He Y, Wu J, Dressman D, Iacobuzio-Donahue C, Markowitz S, Velculescu V . Heteroplasmic mitochondrial DNA mutations in normal and tumour cells. Nature. 2010; 464(7288):610-4. PMC: 3176451. DOI: 10.1038/nature08802. View

18.

Li M, Schonberg A, Schaefer M, Schroeder R, Nasidze I, Stoneking M . Detecting heteroplasmy from high-throughput sequencing of complete human mitochondrial DNA genomes. Am J Hum Genet. 2010; 87(2):237-49. PMC: 2917713. DOI: 10.1016/j.ajhg.2010.07.014. View

19.

Abecasis G, Altshuler D, Auton A, Brooks L, Durbin R, Gibbs R . A map of human genome variation from population-scale sequencing. Nature. 2010; 467(7319):1061-73. PMC: 3042601. DOI: 10.1038/nature09534. View

20.

HUTCHISON 3rd C, Newbold J, Potter S, Edgell M . Maternal inheritance of mammalian mitochondrial DNA. Nature. 1974; 251(5475):536-8. DOI: 10.1038/251536a0. View