title: Features of constitutive gr/gr deletion in a Japanese population.
abstract: BACKGROUND
  The relationship between male infertility and gr/gr deletions that remove multiple genes of the Y chromosome varies among countries and populations. The aim of this study was to investigate the association between gr/gr deletions and spermatogenic phenotype in fertile and infertile Japanese men.
  
  
  METHODS
  The subjects were screened by sequence-tagged site (STS) analysis to detect gr/gr deletions, and haplogroups were assigned using eight highly informative markers. In total, 395 infertile men and 377 fertile men (controls) participated in our study. Of the 772 subjects, 260 individuals carried confirmed gr/gr deletions and were used in further analysis of deletion subtype and gene copy number, specifically loss and gain of CDY1 and DAZ copies. These 260 subjects were divided into a control group (n = 131) all with normozoospermia, and an infertile group (n = 129) with 89 infertile subjects exhibiting azoospermia (absence of sperm) and 40 exhibiting oligozoospermia (reduced sperm concentration).
  
  
  RESULTS
  There were gr/gr deletions in 33.7% (260/772) of all subjects and the deletions were widespread in haplogroup D (86.2%). There were no significant differences in the frequency of gr/gr deletions between the infertile and control groups. The gr/gr deletion subtypes were not distributed randomly among haplogroups; the CDY1a+ DAZ1/2 genes were deleted in 96.9% (217/224) of haplogroup D individuals, whereas the O lineage had a variety of gr/gr deletion types. The loss of CDY1a+ DAZ1/2 was not associated with spermatogenic impairment in haplogroup D (P = 0.33).
  
  
  CONCLUSIONS
  Taken together, gr/gr deletions in haplogroup D occur constitutively, are associated with the loss of CDY1a + DAZ1/2 and are phenotypically neutral. Further studies are needed to establish whether Y-linked compensatory factors outside the AZFc region can counteract the pathogenic effect of a gr/gr deletion in the D lineage.
authors.affiliation: Department of Integrative Cancer Therapy, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
authors.forename: Ho-Su
authors.initials: HS
authors.lastname: Sin
authors.forename: Eitetsu
authors.initials: E
authors.lastname: Koh
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Shigehara
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Yuji
authors.initials: Y
authors.lastname: Maeda
authors.forename: Atsumi
authors.initials: A
authors.lastname: Yoshida
authors.forename: Koichi
authors.initials: K
authors.lastname: Kyono
authors.forename: Mikio
authors.initials: M
authors.lastname: Namiki
mesh_terms: D053713:Azoospermia / Q000235:genetics; D002872:Chromosome Deletion; D041322:Chromosomes, Human, Y / Q000235:genetics; D000075364:Deleted in Azoospermia 1 Protein; D018628:Gene Dosage; D056726:Genetic Association Studies; D005819:Genetic Markers; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D007564:Japan; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D009845:Oligospermia / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics*; D055101:Semen Analysis; D016324:Sequence Tagged Sites; D012729:Sex Chromosome Aberrations; D058533:Sex Chromosome Disorders of Sex Development / Q000235:genetics
chemical_list: C118459:CDY1 protein, human; C095668:DAZ1 protein, human; C459440:DAZ2 protein, human; D000075364:Deleted in Azoospermia 1 Protein; D005819:Genetic Markers; D009687:Nuclear Proteins; D020033:Protein Isoforms; D016601:RNA-Binding Proteins