title: On the frequency of copy number variants.
abstract: BACKGROUND
  Estimating the frequency distribution of copy number variants (CNVs) is an important aspect of the effort to characterize this new type of genetic variation. Currently, most studies report a strong skew toward low-frequency CNVs. In this article, our goal is to investigate the frequencies of CNVs. We employ a two-step procedure for the CNV frequency estimation process. We use family information a posteriori to select only the most reliable CNV regions, i.e. those showing high rates of Mendelian transmission.
  
  
  RESULTS
  Our results suggest that the current skew toward low-frequency CNVs may not be representative of the true frequency distribution, but may be due, among other reasons, to the non-negligible false negative rates that characterize CNV detection methods. Moreover, false positives are also likely, as low-frequency CNVs are hard to detect with small sample sizes and technologies that are not ideally suited for their detection. Without appropriate validation methods, such as incorporation of biologically relevant information (for example, in our case, the transmission of heritable CNVs from parents to offspring), it is difficult to assess the validity of specific CNVs, and even harder to obtain reliable frequency estimates.
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA. iionita@hsph.harvard.edu
authors.forename: Iuliana
authors.initials: I
authors.lastname: Ionita-Laza
authors.forename: Nan M
authors.initials: NM
authors.lastname: Laird
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Raby
authors.forename: Scott T
authors.initials: ST
authors.lastname: Weiss
authors.forename: Christoph
authors.initials: C
authors.lastname: Lange
mesh_terms: D000465:Algorithms; D018628:Gene Dosage / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide