title: [Causal mutation or rare polymorphism? Frequency of mutation not found in 3 chromosome is less than 3 divided by n].
abstract: The problem of distinguishing rare polymorphism from deleterious mutations is an important question in molecular medicine. In order to estimate the frequency of a sequence variation, unrelated normal individuals are usually screened for the mutation concerned. A sequence variation that is not found in non-affected individuals becomes more likely to be the cause of the disease. The aim of this paper is to provide a practical estimation of the fortuitous occurrence of a private polymorphism in one or several patients. The frequency of a sequence variation is not difficult to estimate in a population. The 95% upper frequency limit of a gene variant not observed in n chromosomes is 1-n+1 square root of 0.05. This can conveniently be approximated as 3/n. While the likelihood for finding a sequence variation only in patients is easily calculated, it is practically impossible to compute the exact probability that this variation is indeed the cause of the disease.
authors.affiliation: Unité INSERM U129, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Jeanpierre
mesh_terms: D016001:Confidence Intervals; D005787:Gene Frequency; D030342:Genetic Diseases, Inborn / Q000235:genetics; D006801:Humans; D009154:Mutation; D011110:Polymorphism, Genetic
vernacular_title: Mutation causale ou polymorphisme rare? La fréquence d'une mutation non retrouvée sur n chromosomes est inférieure à 3/n.