Genotypic Stability, Segregation and Selection in Heteroplasmic Human Cell Lines Containing np 3243 Mutant mtDNA

The mitochondrial genotype of heteroplasmic human cell lines containing the pathological np 3243 mtDNA mutation, plus or minus its suppressor at np 12300, has been followed over long periods in culture. Cell lines containing various different proportions of mutant mtDNA remained generally at a consi...

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Bibliographic Details
Published in:Genetics (Austin) 2000-01, Vol.154 (1), p.363-380
Main Authors: Lehtinen, Sanna K, Hance, Nicole, El Meziane, Abdellatif, Juhola, M. Katariina, Juhola, K. Martti I, Karhu, Ritva, Spelbrink, Johannes N, Holt, Ian J, Jacobs, Howard T
Format: Article
Language:English
Subjects:
Base Sequence
Cells
chromosome 9
Cytoskeleton - drug effects
Cytoskeleton - metabolism
Deoxyribonucleic acid
Dimethyl Sulfoxide - pharmacology
DNA
DNA Primers
DNA, Mitochondrial - genetics
Genetics
Genotype
heteroplasmy
Humans
Mutation
Phenotype
Selection, Genetic
Tumor Cells, Cultured
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Summary:The mitochondrial genotype of heteroplasmic human cell lines containing the pathological np 3243 mtDNA mutation, plus or minus its suppressor at np 12300, has been followed over long periods in culture. Cell lines containing various different proportions of mutant mtDNA remained generally at a consistent, average heteroplasmy value over at least 30 wk of culture in nonselective media and exhibited minimal mitotic segregation, with a segregation number comparable with mtDNA copy number (>/=1000). Growth in selective medium of cells at 99% np 3243 mutant mtDNA did, however, allow the isolation of clones with lower levels of the mutation, against a background of massive cell death. As a rare event, cell lines exhibited a sudden and dramatic diversification of heteroplasmy levels, accompanied by a shift in the average heteroplasmy level over a short period (
ISSN:0016-6731
1943-2631
1943-2631
DOI:10.1093/genetics/154.1.363