title: What is a 'novel' mtDNA mutation--and does 'novelty' really matter?
abstract: The hunt for pathogenic mitochondrial DNA (mtDNA) mutations is often fueled by the seeming novelty of mutations that are either nonsynonymous or affect the protein synthesis machinery in patients. In order to determine the novelty of a detected mutation, the working geneticist nearly always consults MITOMAP--often exclusively. By reanalyzing some case studies of refractory anemia with ring sideroblasts, prostate cancer, and hearing impairment, we demonstrate that the practice of solely relying on MITOMAP can be most misleading. A notorious example is the T1243C mutation, which was assessed to be novel and deemed to be associated with some (rare) disease simply because researchers did not realize that T1243C defines a deep branch in the Eurasian mtDNA phylogeny. The majority of 'novel' mutations suspected of being pathogenic are in actual fact known (and presumably neutral) polymorphisms (although unknown to MITOMAP), and this becomes glaringly evident when proper database searches and straightforward Internet queries are carried out.
authors.affiliation: Department of Mathematics, University of Hamburg, Bundesstr. 55, 20146, Hamburg, Germany. bandelt@math.uni-hamburg.de.
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Bandelt
authors.affiliation: Unidad de Genética, Instituto de Medicina Legal, Facultad de Medicina, Universidad de Santiago de Compostela, 15782, Galicia, Spain.|Centro Nacional de Genotipado (CeGen), Hospital Clínico Universitario, 15706, Galicia, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Salas
authors.affiliation: Laboratorio de Genética Molecular Poblacional, Instituto Multidisciplinario de Biología Celular (IMBICE), P.O. Box 403, 1900, La Plata, Argentina.
authors.forename: Claudio M
authors.initials: CM
authors.lastname: Bravi
mesh_terms: D000754:Anemia, Refractory, with Excess of Blasts / Q000235:genetics; D004272:DNA, Mitochondrial / Q000737:chemistry*; D030541:Databases, Genetic; D014644:Genetic Variation; D015894:Genome, Human; D034381:Hearing Loss / Q000235:genetics; D006801:Humans; D020407:Internet; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial