Differential effect of specific gr/gr deletion subtypes on spermatogenesis in the Chinese Han population

As a common variation in the azoospermia factor c (AZFc) region of Y chromosome, the gr/gr deletion is regarded as a significant risk factor for spermatogenic impairment, whereas the association of the deletion's phenotypic expression with Y-chromosomal background is still a subject of debate. To further investigate the contribution of the deletion to spermatogenic impairment in different Y-chromosomal haplogroups, the partial AZFc deletion was detected with AZFc-specific sequence tagged sites, gene dosage and gene copy analyses of deleted in azoospermia (DAZ), chromodomain Y1 (CDY1) and basic protein Y2 (BPY2) in 1426 azoo/oligozoospermic and 672 normozoospermic men from a Chinese population. The haplogrouping was performed in 231 deletion carriers with 12 polymorphic loci of Y chromosome. As a result, five gr/gr rearrangement types in eight Y haplogroups were observed, in which the simple gr/gr deletion was the most common type, and its frequency was significantly higher in men with azoo/oligozoospermia relative to normozoospermia. Also the distribution of gr/gr-rearranged Y haplogroups was significantly different between the two groups, in which gr/gr-deleted haplogroups C and DE were more common in men with azoo/oligozoospermia. In the 6 gr/gr copy deletion haplotypes, the frequencies of DAZ1/DAZ2+CDY1a or CDY1b deletion were significantly higher in men with azoo/oligozoospermia, while all DAZ3/-DAZ4+CDY1b+BPY2.2 or 2.3 deletions were found only in haplogroup Q1 without any distribution difference between the azoo/oligozoospermic and normozoospermic groups. This study provided further evidence for the existence of multiple subtypes of gr/gr deletion and indicates that gr/gr-DAZ1/DAZ2 deletion is a significant risk factor. However, the association of the phenotypic variation of gr/gr deletion with Y-chromosomal haplogroups is not definite yet, because of the limited amounts of the deletions observed in each of the haplogroups and the lack of the quantitative trait analyses such as sperm density analysis. The fact that a common gr/gr copy deletion haplotype was found exclusively in the Y hgr Q1, without pathogenic consequences, implies the importance of haplogrouping and of copy deletion typing prior to genetic counselling of deletion carriers of Chinese descent.