title: Analysis of X chromosome genomic DNA sequence copy number variation associated with premature ovarian failure (POF).
abstract: BACKGROUND
  Premature ovarian failure (POF) is a heterogeneous disease defined as amenorrhoea for >6 months before age 40, with an FSH serum level >40 mIU/ml (menopausal levels). While there is a strong genetic association with POF, familial studies have also indicated that idiopathic POF may also be genetically linked. Conventional cytogenetic analyses have identified regions of the X chromosome that are strongly associated with ovarian function, as well as several POF candidate genes. Cryptic chromosome abnormalities that have been missed might be detected by array comparative genomic hybridization.
  
  
  METHODS
  In this study, samples from 42 idiopathic POF patients were subjected to a complete end-to-end X/Y chromosome tiling path array to achieve a detailed copy number variation (CNV) analysis of X chromosome involvement in POF. The arrays also contained a 1 Mb autosomal tiling path as a reference control. Quantitative PCR for selected genes contained within the CNVs was used to confirm the majority of the changes detected. The expression pattern of some of these genes in human tissue RNA was examined by reverse transcription (RT)-PCR.
  
  
  RESULTS
  A number of CNVs were identified on both Xp and Xq, with several being shared among the POF cases. Some CNVs fall within known polymorphic CNV regions, and others span previously identified POF candidate regions and genes.
  
  
  CONCLUSIONS
  The new data reported in this study reveal further discrete X chromosome intervals not previously associated with the disease and therefore implicate new clusters of candidate genes. Further studies will be required to elucidate their involvement in POF.
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
authors.forename: C R
authors.initials: CR
authors.lastname: Quilter
authors.forename: A C
authors.initials: AC
authors.lastname: Karcanias
authors.forename: M R
authors.initials: MR
authors.lastname: Bagga
authors.forename: S
authors.initials: S
authors.lastname: Duncan
authors.forename: A
authors.initials: A
authors.lastname: Murray
authors.forename: G S
authors.initials: GS
authors.lastname: Conway
authors.forename: C A
authors.initials: CA
authors.lastname: Sargent
authors.forename: N A
authors.initials: NA
authors.lastname: Affara
mesh_terms: D000328:Adult; D041321:Chromosomes, Human, X; D055028:Comparative Genomic Hybridization; D005260:Female; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D005810:Multigene Family; D016133:Polymerase Chain Reaction; D016649:Primary Ovarian Insufficiency / Q000235:genetics*