Segregation of the ND4/11778 and the ND1/3460 mutations in four heteroplasmic LHON families

Puomila, Anu; Viitanen, Tommi; Savontaus, Marja-Liisa; Nikoskelainen, Eeva; Huoponen, Kirsi

« Previous Next »Journal of the Neurological Sciences
Volume 205, Issue 1 , Pages 41-45, 15 December 2002

Segregation of the ND4/11778 and the ND1/3460 mutations in four heteroplasmic LHON families

Anu Puomila
- Corresponding author. Department of Medical Genetics, University of Turku, Kiinamyllynkatu 10, FIN-20520 Turku, Finland. Tel.: +358-2-333-7456; fax: +358-2-333-7300.
- Department of Medical Genetics, University of Turku, Turku, Finland
- Laboratory of Genetics, Department of Biology, University of Turku, Turku, Finland
Tommi Viitanen
- Department of Statistics, University of Turku, Turku, Finland
Marja-Liisa Savontaus
- Department of Medical Genetics, University of Turku, Turku, Finland
- Laboratory of Genetics, Department of Biology, University of Turku, Turku, Finland
Eeva Nikoskelainen
- Department of Ophthalmology, Turku University Central Hospital, Turku, Finland
Kirsi Huoponen
- Department of Medical Genetics, University of Turku, Turku, Finland
- Laboratory of Genetics, Department of Biology, University of Turku, Turku, Finland

Received 28 May 2002; received in revised form 24 July 2002; accepted 25 July 2002.

Abstract

Leber hereditary optic neuropathy (LHON) is an ocular disease associated with mutations in the mitochondrial DNA (mtDNA). The level of heteroplasmy in the mtDNA mutations ND4/11778 and ND1/3460 was followed over a period of 4–12 years in blood samples taken from nine members of four heteroplasmic LHON families. In addition, hair follicle and urinary tract epithelium samples of one individual were studied. The quantification of heteroplasmy was performed using the solid-phase minisequencing method. Only minor and random shifts in the heteroplasmy levels were observed over time, but there were no systematic changes towards an increasing or decreasing proportion of either LHON mutant in the individuals. This indicates that there is no selection for either mtDNA genotype but the segregation of the wild-type mtDNAs and those carrying LHON mutations is a stochastic process governed by random genetic drift. In this respect, LHON mutations seem to behave like neutral polymorphisms.

Keywords: Leber hereditary optic neuropathy, Mitochondrial DNA, Heteroplasmy, Mitotic segregation, Longitudinal analysis