title: The Y chromosome gr/gr subdeletion is associated with male infertility.
abstract: Men with Y chromosome (Yq) AZFc deletions lack all copies of the DAZ gene and have severe spermatogenic failure. A recently described gr/gr subdeletion of AZFc removes two of four copies of DAZ. To better understand the relative frequencies of AZFc and gr/gr deletions and their associated phenotypes, we analysed two large groups of infertile men. A total of 788 men from the Monash Male Infertility (MMI) database with a range of fertility disorders showed similar overall prevalences of AZFc (2.5%) and gr/gr deletions (3.4%). There was no association of gr/gr deletions with sperm density. In 234 control men of known or presumed fertility, only one gr/gr deletion was found. In a further 599 consecutive men presenting for assisted reproductive technologies, we detected 13 (2.2%) AZFc deletions and 28 (4.7%) gr/gr deletions. All AZFc deletions were seen with sperm densities <5 million/ml but again the gr/gr deletion occurred with similar frequency across all sperm density categories. These data show that gr/gr deletions are significantly associated with infertility in the Australian population (P = 0.0015) but not exclusively with reduced sperm density suggesting a complex interaction with other factors important for male fertility. Vertical transmission of gr/gr deletions from father to son by ICSI was demonstrated in four cases. Analysis of 130 ICSI-conceived sons revealed no de novo gr/gr deletions indicating that ICSI is not a risk factor. The data suggest that testing for gr/gr deletions should be considered in the routine genetic assessment of men with idiopathic infertility.
authors.affiliation: Prince Henry's Institute of Medical Research, Monash University, Monash Medical Centre, Clayton, Victoria, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Lynch
authors.forename: D S
authors.initials: DS
authors.lastname: Cram
authors.forename: A
authors.initials: A
authors.lastname: Reilly
authors.forename: M K
authors.initials: MK
authors.lastname: O'Bryan
authors.forename: H W G
authors.initials: HW
authors.lastname: Baker
authors.forename: D M
authors.initials: DM
authors.lastname: de Kretser
authors.forename: R I
authors.initials: RI
authors.lastname: McLachlan
mesh_terms: D002872:Chromosome Deletion; D041322:Chromosomes, Human, Y / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007248:Infertility, Male / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D015995:Prevalence; D020554:Sperm Injections, Intracytoplasmic