Imperial College London
Alternate

Nick S Jones

Faculty of Natural Sciences, Department of Mathematics

Professor of Mathematical Sciences
 
 
 
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Contact

 

+44 (0)20 7594 1146nick.jones

 
 
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Location

 

301aSir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Zhang:2021:10.1126/sciadv.abi5657,
author = {Zhang, H and Esposito, M and Pezet, MG and Aryaman, J and Wei, W and Klimm, F and Calabrese, C and Burr, SP and Macabelli, CH and Viscomi, C and Saitou, M and Chiaratti, MR and Stewart, JB and Jones, N and Chinnery, PF},
doi = {10.1126/sciadv.abi5657},
journal = {Science Advances},
pages = {1--12},
title = {Mitochondrial DNA heteroplasmy is modulated during oocyte development propagating mutation transmission},
url = {http://dx.doi.org/10.1126/sciadv.abi5657},
volume = {7},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Heteroplasmic mitochondrial DNA (mtDNA) mutations are a common cause of inherited disease, but a few recurrent mutations account for the vast majority of new families. The reasons for this are not known. We studied heteroplasmic mice transmitting m.5024C>T corresponding to a human pathogenic mutation. Analyzing 1167 mother-pup pairs, we show that m.5024C>T is preferentially transmitted from low to higher levels but does not reach homoplasmy. Single-cell analysis of the developing mouse oocytes showed the preferential increase in mutant over wild-type mtDNA in the absence of cell division. A similar inheritance pattern is seen in human pedigrees transmitting several pathogenic mtDNA mutations. In m.5024C>T mice, this can be explained by the preferential propagation of mtDNA during oocyte maturation, counterbalanced by purifying selection against high heteroplasmy levels. This could explain how a disadvantageous mutation in a carrier increases to levels that cause disease but fails to fixate, causing multigenerational heteroplasmic mtDNA disorders.
AU  - Zhang,H
AU  - Esposito,M
AU  - Pezet,MG
AU  - Aryaman,J
AU  - Wei,W
AU  - Klimm,F
AU  - Calabrese,C
AU  - Burr,SP
AU  - Macabelli,CH
AU  - Viscomi,C
AU  - Saitou,M
AU  - Chiaratti,MR
AU  - Stewart,JB
AU  - Jones,N
AU  - Chinnery,PF
DO  - 10.1126/sciadv.abi5657
EP  - 12
PY  - 2021///
SN  - 2375-2548
SP  - 1
TI  - Mitochondrial DNA heteroplasmy is modulated during oocyte development propagating mutation transmission
T2  - Science Advances
UR  - http://dx.doi.org/10.1126/sciadv.abi5657
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000728174000008&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.science.org/doi/10.1126/sciadv.abi5657
UR  - http://hdl.handle.net/10044/1/93484
VL  - 7
ER  -
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