title: Phenotypic variation within European carriers of the Y-chromosomal gr/gr deletion is independent of Y-chromosomal background.
abstract: BACKGROUND
  Previous studies have compared sperm phenotypes between men with partial deletions within the AZFc region of the Y chromosome and non-carriers, with variable results. In this study, a separate question was investigated, the basis of the variation in sperm phenotype within gr/gr deletion carriers, which ranges from normozoospermia to azoospermia. Differences in the genes removed by independent gr/gr deletions, the occurrence of subsequent duplications or the presence of linked modifying variants elsewhere on the chromosome have been suggested as possible causal factors. This study set out to test these possibilities in a large sample of gr/gr deletion carriers with known phenotypes spanning the complete range.
  
  
  RESULTS
  In total, 169 men diagnosed with gr/gr deletions from six centres in Europe and one in Australia were studied. The DAZ and CDY1 copies retained, the presence or absence of duplications and the Y-chromosomal haplogroup were characterised. Although the study had good power to detect factors that accounted for >or=5.5% of the variation in sperm concentration, no such factor was found. A negative effect of gr/gr deletions followed by b2/b4 duplication was found within the normospermic group, which remains to be further explored in a larger study population. Finally, significant geographical differences in the frequency of different subtypes of gr/gr deletions were found, which may have relevance for the interpretation of case control studies dealing with admixed populations.
  
  
  CONCLUSIONS
  The phenotypic variation of gr/gr carriers in men of European origin is largely independent of the Y-chromosomal background.
authors.affiliation: Andrology Unit, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini, 6 Florence 50139, Italy. c.krausz@dfc.unifi.it
authors.forename: C
authors.initials: C
authors.lastname: Krausz
authors.forename: C
authors.initials: C
authors.lastname: Giachini
authors.forename: Y
authors.initials: Y
authors.lastname: Xue
authors.forename: M K
authors.initials: MK
authors.lastname: O'Bryan
authors.forename: J
authors.initials: J
authors.lastname: Gromoll
authors.forename: E
authors.initials: E
authors.lastname: Rajpert-de Meyts
authors.forename: R
authors.initials: R
authors.lastname: Oliva
authors.forename: I
authors.initials: I
authors.lastname: Aknin-Seifer
authors.forename: E
authors.initials: E
authors.lastname: Erdei
authors.forename: N
authors.initials: N
authors.lastname: Jorgensen
authors.forename: M
authors.initials: M
authors.lastname: Simoni
authors.forename: J L
authors.initials: JL
authors.lastname: Ballescà
authors.forename: R
authors.initials: R
authors.lastname: Levy
authors.forename: G
authors.initials: G
authors.lastname: Balercia
authors.forename: P
authors.initials: P
authors.lastname: Piomboni
authors.forename: E
authors.initials: E
authors.lastname: Nieschlag
authors.forename: G
authors.initials: G
authors.lastname: Forti
authors.forename: R
authors.initials: R
authors.lastname: McLachlan
authors.forename: C
authors.initials: C
authors.lastname: Tyler-Smith
mesh_terms: D001315:Australia; D002872:Chromosome Deletion; D041322:Chromosomes, Human, Y / Q000235:genetics*; D000075364:Deleted in Azoospermia 1 Protein; D005060:Europe; D018628:Gene Dosage; D056426:Genetic Loci; D014644:Genetic Variation; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008297:Male; D008957:Models, Genetic; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D016601:RNA-Binding Proteins / Q000235:genetics; D012661:Semen / Q000378:metabolism; D029589:Seminal Plasma Proteins / Q000235:genetics; D044465:White People / Q000235:genetics*
chemical_list: C118459:CDY1 protein, human; C485564:CDY2A protein, human; C095668:DAZ1 protein, human; C101358:DAZL protein, human; D000075364:Deleted in Azoospermia 1 Protein; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D029589:Seminal Plasma Proteins
references.citation: Science. 2000 Nov 10;290(5494):1155-9
references.pmid: 11073453
references.citation: Asian J Androl. 2007 Nov;9(6):815-20
references.pmid: 17968468
references.citation: Fertil Steril. 2006 Jan;85(1):229-31
references.pmid: 16412764
references.citation: Am J Hum Genet. 2000 Dec;67(6):1526-43
references.pmid: 11078479
references.citation: Hum Reprod. 2007 Sep;22(9):2398-403
references.pmid: 17609244
references.citation: Nat Genet. 2003 Nov;35(3):247-51
references.pmid: 14528305
references.citation: Arch Androl. 2007 May-Jun;53(3):125-33
references.pmid: 17612870
references.citation: Int J Androl. 2004 Dec;27(6):375-81
references.pmid: 15595957
references.citation: Hum Reprod Update. 2005 Jul-Aug;11(4):319-36
references.pmid: 15890785
references.citation: J Med Genet. 2005 Mar;42(3):209-13
references.pmid: 15744033
references.citation: Mol Hum Reprod. 2002 Mar;8(3):286-98
references.pmid: 11870237
references.citation: Nat Genet. 2006 Apr;38(4):463-7
references.pmid: 16501575
references.citation: J Med Genet. 2005 Jun;42(6):497-502
references.pmid: 15937085
references.citation: Genome Res. 2008 May;18(5):830-8
references.pmid: 18385274
references.citation: Front Biosci. 2006 Sep 01;11:3049-61
references.pmid: 16720375
references.citation: Nucleic Acids Res. 2002 Mar 15;30(6):e27
references.pmid: 11884646
references.citation: Nature. 2003 Jun 19;423(6942):825-37
references.pmid: 12815422
references.citation: Curr Opin Genet Dev. 2006 Jun;16(3):225-32
references.pmid: 16650761
references.citation: Mol Hum Reprod. 2005 Jul;11(7):507-12
references.pmid: 16123079
references.citation: Hum Reprod. 2005 Jan;20(1):216-20
references.pmid: 15513974
references.citation: J Med Genet. 2004 Nov;41(11):814-25
references.pmid: 15520406
references.citation: Hum Mutat. 2007 May;28(5):486-94
references.pmid: 17285591
references.citation: Nat Genet. 2001 Nov;29(3):243-4
references.pmid: 11687786
references.citation: Am J Hum Genet. 1999 Apr;64(4):928-33
references.pmid: 10090876
references.citation: Mol Hum Reprod. 2006 Apr;12(4):269-73
references.pmid: 16597640
references.citation: Hum Reprod. 2005 Jan;20(1):191-7
references.pmid: 15498781
references.citation: Hum Mol Genet. 1996 Nov;5(11):1767-75
references.pmid: 8923005
references.citation: Reprod Biomed Online. 2007 Dec;15(6):643-58
references.pmid: 18062861