What is a ovel mtDNA mutation–and does ovelty really matter?
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
Related Questions
- Why does a mutation that deletes one or two DNA nucleotides changes gene function more drastically than a substitution of one nucleotide for another type?
- What type of mutation could result from a deletion of a single nucleotide from the DNA sequence?
- What is a mutation in which only one nucleotide or nitrogenous base in a gene is changed?
