title: Defining "mutation" and "polymorphism" in the era of personal genomics.
abstract: BACKGROUND
  The growing advances in DNA sequencing tools have made analyzing the human genome cheaper and faster. While such analyses are intended to identify complex variants, related to disease susceptibility and efficacy of drug responses, they have blurred the definitions of mutation and polymorphism.
  
  
  CONCLUSIONS
  In the era of personal genomics, it is critical to establish clear guidelines regarding the use of a reference genome. Nowadays DNA variants are called as differences in comparison to a reference. In a sequencing project Single Nucleotide Polymorphisms (SNPs) and DNA mutations are defined as DNA variants detectable in >1 % or <1 % of the population, respectively. The alternative use of the two terms mutation or polymorphism for the same event (a difference as compared with a reference) can lead to problems of classification. These problems can impact the accuracy of the interpretation and the functional relationship between a disease state and a genomic sequence. We propose to solve this nomenclature dilemma by defining mutations as DNA variants obtained in a paired sequencing project including the germline DNA of the same individual as a reference. Moreover, the term mutation should be accompanied by a qualifying prefix indicating whether the mutation occurs only in somatic cells (somatic mutation) or also in the germline (germline mutation). We believe this distinction in definition will help avoid confusion among researchers and support the practice of sequencing the germline and somatic tissues in parallel to classify the DNA variants thus defined as mutations.
authors.affiliation: Danbury Hospital Research Institute, Western Connecticut Health Network, 131 West Street, Danbury, CT, 06810, USA.
authors.forename: Roshan
authors.initials: R
authors.lastname: Karki
authors.affiliation: Danbury Hospital Research Institute, Western Connecticut Health Network, 131 West Street, Danbury, CT, 06810, USA.
authors.forename: Deep
authors.initials: D
authors.lastname: Pandya
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Elston
authors.affiliation: Danbury Hospital Research Institute, Western Connecticut Health Network, 131 West Street, Danbury, CT, 06810, USA. Cristiano.ferlini@wchn.org.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Ferlini
mesh_terms: D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D015894:Genome, Human / Q000235:genetics; D023281:Genomics / Q000379:methods*; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D009626:Terminology as Topic
chemical_list: D004247:DNA