High penetrance of sequencing errors and interpretative shortcomings in mtDNA

BANDELT HJ; YAO YG; SALAS A; KIVISILD T; BRAVI CM

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

ACADEMIC PRESS INC ELSEVIER SCIENCE

Lugar: Amsterdam; Año: 2007 vol. 352 p. 283 - 291

0006-291X

For identifying mutation(s) that are potentially pathogenic it is essential to determine the entire mitochondrial DNA (mtDNA) sequences from patients suffering from a particular mitochondrial disease, such as Leber hereditary optic neuropathy (LHON). However, such sequencing efforts can, in the worst case, be riddled with errors by imposing phantom mutations or misreporting variant nucleotides, and moreover, by inadvertently regarding some mutations as novel and pathogenic, which are actually known to define minor haplogroups. Under such circumstances it remains unclear whether the disease-associated mutations would have been determined adequately. Here, we re-analyse four problematic LHON studies and propose guidelines by which some of the pitfalls could be avoided.