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

Elsevier

Año: 2007 vol. 352 p. 283 - 291

For identifying mutation(s) that are potentially pathogenic it is essential todetermine the entire mitochondrial DNA (mtDNA) sequences from patients sufferingfrom a particular mitochondrial disease, such as Leber hereditary opticneuropathy (LHON). However, such sequencing efforts can, in the worst case, beriddled with errors by imposing phantom mutations or misreporting variantnucleotides, and moreover, by inadvertently regarding some mutations as noveland pathogenic, which are actually known to define minor haplogroups. Under suchcircumstances it remains unclear whether the disease-associated mutations wouldhave been determined adequately. Here, we re-analyse four problematic LHONstudies and propose guidelines by which some of the pitfalls could be avoided.