Universität zu Köln

Freyer, Christoph ORCID: 0000-0003-0418-1673, Cree, Lynsey M., Mourier, Arnaud, Stewart, James B., Koolmeister, Camilla, Milenkovic, Dusanka, Wai, Timothy ORCID: 0000-0002-6770-6222, Floros, Vasileios I., Hagstrom, Erik, Chatzidaki, Emmanouella E., Wiesner, Rudolf J., Samuels, David C., Larsson, Nils-Goeran and Chinnery, Patrick F. (2012). Variation in germline mtDNA heteroplasmy is determined prenatally but modified during subsequent transmission. Nature Genet., 44 (11). S. 1282 - 1286. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1546-1718

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Abstract

A genetic bottleneck explains the marked changes in mitochondria! DNA (mtDNA) heteroplasmy that are observed during the transmission of pathogenic mutations, but the precise timing of these changes remains controversial, and it is not clear whether selection has a role. These issues are important for the genetic counseling of prospective mothers and for the development of treatments aimed at disease prevention. By studying mice transmitting a heteroplasmic single-base-pair deletion in the mitochondrial tRNA(Met) gene, we show that the extent of mammalian mtDNA heteroplasmy is principally determined prenatally within the developing female germline. Although we saw no evidence of mtDNA selection prenatally, skewed heteroplasmy levels were observed in the offspring of the next generation, consistent with purifying selection. High percentages of mtDNA genomes with the tRNAMet mutation were linked to a compensatory increase in overall mitochondrial RNA levels, ameliorating the biochemical phenotype and explaining why fecundity is not compromised.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Freyer, Christoph UNSPECIFIED orcid.org/0000-0003-0418-1673 UNSPECIFIED Cree, Lynsey M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mourier, Arnaud UNSPECIFIED UNSPECIFIED UNSPECIFIED Stewart, James B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Koolmeister, Camilla UNSPECIFIED UNSPECIFIED UNSPECIFIED Milenkovic, Dusanka UNSPECIFIED UNSPECIFIED UNSPECIFIED Wai, Timothy UNSPECIFIED orcid.org/0000-0002-6770-6222 UNSPECIFIED Floros, Vasileios I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hagstrom, Erik UNSPECIFIED UNSPECIFIED UNSPECIFIED Chatzidaki, Emmanouella E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiesner, Rudolf J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Samuels, David C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Larsson, Nils-Goeran UNSPECIFIED UNSPECIFIED UNSPECIFIED Chinnery, Patrick F. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-480631
DOI:	10.1038/ng.2427
Journal or Publication Title:	Nature Genet.
Volume:	44
Number:	11
Page Range:	S. 1282 - 1286
Date:	2012
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	NEW YORK
ISSN:	1546-1718
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MITOCHONDRIAL-DNA HETEROPLASMY; PURIFYING SELECTION; MUTATION; SEGREGATION; REDUCTION; EVOLUTION; DRIFT; MICE Multiple languages Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48063