title: Genomic and genetic variation in E2F transcription factor-1 in men with nonobstructive azoospermia.
abstract: OBJECTIVE
  To identify gene dosage changes associated with nonobstructive azoospermia (NOA) using array comparative genomic hybridization (aCGH).
  
  
  METHODS
  Prospective study.
  
  
  METHODS
  Medical school.
  
  
  METHODS
  One hundred ten men with NOA and 78 fertile controls.
  
  
  METHODS
  None.
  
  
  METHODS
  The study has four distinct analytic components: aCGH, a molecular karyotype that detects copy number variations (CNVs); Taqman CNV assays to validate CNVs; mutation identification by Sanger sequencing; and histological analyses of testicular tissues.
  
  
  RESULTS
  A microduplication at 20q11.22 encompassing E2F transcription factor-1 (E2F1) was identified in one of eight men with NOA analyzed using aCGH. CNVs were confirmed and in an additional 102 men with NOA screened using Taqman CNV assays, for a total of 110 NOA men analyzed for CNVs in E2F1. Eight of 110 (7.3%) NOA men had microduplications or microdeletions of E2F1 that were absent in fertile controls.
  
  
  CONCLUSIONS
  E2F1 microduplications or microdeletions are present in men with NOA (7.3%). Duplications or deletions of E2F1 occur very rarely in the general population (0.011%), but E2F1 gene dosage changes, previously reported only in cancers, are present in a subset of NOA men. These results recapitulate the infertility phenotype seen in mice lacking or overexpressing E2f1.
authors.affiliation: Center for Reproductive Medicine, Baylor College of Medicine, Houston, Texas; Scott Department of Urology, Baylor College of Medicine, Houston, Texas. Electronic address: cj129804@bcm.edu.
authors.forename: Carolina J
authors.initials: CJ
authors.lastname: Jorgez
authors.affiliation: Center for Reproductive Medicine, Baylor College of Medicine, Houston, Texas; Scott Department of Urology, Baylor College of Medicine, Houston, Texas.
authors.forename: Nathan
authors.initials: N
authors.lastname: Wilken
authors.affiliation: Center for Reproductive Medicine, Baylor College of Medicine, Houston, Texas; Scott Department of Urology, Baylor College of Medicine, Houston, Texas.
authors.forename: Josephine B
authors.initials: JB
authors.lastname: Addai
authors.affiliation: Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, Texas.
authors.forename: Justin
authors.initials: J
authors.lastname: Newberg
authors.affiliation: Scott Department of Urology, Baylor College of Medicine, Houston, Texas.
authors.forename: Hima V
authors.initials: HV
authors.lastname: Vangapandu
authors.affiliation: Center for Reproductive Medicine, Baylor College of Medicine, Houston, Texas; Scott Department of Urology, Baylor College of Medicine, Houston, Texas.
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Pastuszak
authors.affiliation: Scott Department of Urology, Baylor College of Medicine, Houston, Texas.
authors.forename: Sarmistha
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Signature Genomic Laboratories, PerkinElmer, Inc., Spokane, Washington.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Rosenfeld
authors.affiliation: Center for Reproductive Medicine, Baylor College of Medicine, Houston, Texas; Scott Department of Urology, Baylor College of Medicine, Houston, Texas.
authors.forename: Larry I
authors.initials: LI
authors.lastname: Lipshultz
authors.affiliation: Center for Reproductive Medicine, Baylor College of Medicine, Houston, Texas; Scott Department of Urology, Baylor College of Medicine, Houston, Texas; Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, Texas.
authors.forename: Dolores J
authors.initials: DJ
authors.lastname: Lamb
mesh_terms: D000328:Adult; D000818:Animals; D053713:Azoospermia / Q000453:epidemiology* / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics; D050687:E2F1 Transcription Factor / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D009154:Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D012307:Risk Factors; D013045:Species Specificity; D013781:Texas / Q000453:epidemiology
chemical_list: D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D005819:Genetic Markers
keywords: Azoospermia; E2F1; NOA; array comparative genomic hybridization (aCGH); copy number variations (CNV); cryptorchidism; infertility