Y chromosome microdeletions, in azoospermic or near-azoospermic subjects, are located in the AZFc (DAZ) subregion

Submicroscopic deletions of the Y chromosome and polymorphisms of theandrogen receptor (AR) gene in the X chromosome have been observed in menwith defective spermatogenesis. To further define the subregions/genes inthe Y chromosome causing male infertility and its relationship topolymorphisms of the AR polyglutamine tract, we screened the genomic DNA of202 subfertile males and 101 healthy fertile controls of predominantlyChinese ethnic origin. Y microdeletions were examined with 16sequence-tagged site (STS) probes, including the RBM and DAZ genes,spanning the AZFb and AZFc subregions of Yq11, and related to the size oftrinucleotide repeat encoding the AR polyglutamine tract. Y microdeletionswere detected and confirmed in three out of 44 (6.8%) of azoospermic andthree out of 86 (3.5%) severely oligozoospermic patients. No deletions weredetected in any of the patients with sperm counts of >0.5 x 10(6)/ml,nor in any of the 101 fertile controls. All six affected patients hadalmost contiguous Y microdeletions spanning the entire AZFc regionincluding the DAZ gene. The AZFb region, containing the RBM1 gene, wasintact in five of the six subjects. Y deletions were not found in thosewith long AR polyglutamine tracts. Our study, the first in a Chinesepopulation, suggest a cause and effect relationship between Ymicrodeletions in the AZFc region (possibly DAZ), and azoospermia ornear-azoospermia. Y microdeletions and long AR polyglutamine tracts appearto be independent contributors to male infertility.