title: Identification of a 2244 base pair interstitial deletion within the human ESR1 gene in the Spanish population.
abstract: BACKGROUND
  The ESR1 AGATA haplotype is composed of five markers located within introns 5 and 6 of the human oestrogen receptor 1 (ESR1) gene. This haplotype has been studied in several male urogenital tract anomalies and male infertility. In one of these studies, a deviation from Hardy-Weinberg equilibrium (DHW) was found for the ESR1 AGATA marker rs3020375 in two groups of healthy controls. In the present study, we investigated whether the observed DHW is caused by structural variants present within the ESR1 gene.
  
  
  METHODS
  229 family units achieving pregnancy through assisted reproductive technologies (n = 129) or by natural means (n = 100), 2465 general Spanish population controls and 162 men with idiopathic infertility.
  
  
  METHODS
  Segregation analyses of genetic markers in family units and case-control genetic association studies.
  
  
  RESULTS
  We identified a new interstitial deletion of 2244 base pairs within intron 6 of the human ESR1 gene as the cause for the observed DHW. This new variant presents a 10% allelic frequency in the general Spanish population and it is associated with idiopathic male infertility (OR = 1.51; p = 0.03). The percentage of infertile couples in which both members carried the ESR1 deletion (10.08%) was also a higher than expected value of 6% (p = 0.03).
  
  
  CONCLUSIONS
  We have characterised a novel structural variation in human ESR1 gene. The available data indicate a deleterious action of the ESR1 deletion in both male and couple fertility. The potential effects of this deletion on other oestrogen-related diseases need to be determined.
authors.affiliation: Department of Structural Genomics, Neocodex SL, Seville, Spain. jjgalan@neocodex.es
authors.forename: J Jorge
authors.initials: JJ
authors.lastname: Galan
authors.forename: B
authors.initials: B
authors.lastname: Buch
authors.forename: S
authors.initials: S
authors.lastname: Pedrinaci
authors.forename: P
authors.initials: P
authors.lastname: Jimenez-Gamiz
authors.forename: A
authors.initials: A
authors.lastname: Gonzalez
authors.forename: M
authors.initials: M
authors.lastname: Serrano-Rios
authors.forename: A
authors.initials: A
authors.lastname: Salinas
authors.forename: M del Carmen
authors.initials: Mdel C
authors.lastname: Rivero
authors.forename: L M
authors.initials: LM
authors.lastname: Real
authors.forename: J L
authors.initials: JL
authors.lastname: Royo
authors.forename: A
authors.initials: A
authors.lastname: Ruiz
mesh_terms: D001483:Base Sequence; D016022:Case-Control Studies; D015331:Cohort Studies; D004247:DNA / Q000737:chemistry / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D014644:Genetic Variation; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008969:Molecular Sequence Data; D016017:Odds Ratio; D010375:Pedigree; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion; D013030:Spain
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D005819:Genetic Markers; D004247:DNA