The b2/b3 subdeletion shows higher risk of spermatogenic failure and higher frequency of complete AZFc deletion than the gr/gr subdeletion in a Chinese population

Abstract

Microdeletions in the azoospermia factor (AZF) regions on the long arm of the human Y chromosome are known to be associated with spermatogenic failure. Although AZFc is recurrently deleted in azoospermic or oligozoospermic males, no definitive conclusion has been reached for the contribution of different partial AZFc deletions to spermatogenic failure. To further investigate the roles of partial deletions in spermatogenic failure and the relationship between the complete and partial AZFc deletions, we performed deletion typing and Y chromosome haplogrouping in 756 idiopathic infertile Han-Chinese and 391 healthy Han-Chinese. We found that both the b2/b3 partial deletion and the DAZ3/4+CDY1a deletion pattern were associated with spermatogenic failure. We also confirmed that two previously reported fixations, the b2/b3 deletion in haplogroup N1 and the gr/gr deletion in haplogroup Q1. Remarkably, the frequency of the complete AZFc deletion in haplogroup N1 was significantly higher than that in the haplogroup Q1. These results suggest that the b2/b3 partial deletion was associated with a higher risk of complete AZFc deletion compared with the gr/gr partial deletion. Compared with the gr/gr deletion, the b2/b3 deletion presents a shorter distance among recombination targets and longer recombination substrates, which may be responsible for the increased incidence of subsequent recombination events that can lead to the complete AZFc deletion in this Chinese study population. The susceptibility of the b2/b3 partial deletion to the complete AZFc deletion deserves further investigation in larger and diverse populations, especially those with a relatively high frequency of b2/b3 and gr/gr partial deletions.

Clinical relevance of Y-linked CNV screening in male infertility: new insights based on the 8-year experience of a diagnostic genetic laboratory

“…This issue is of particular importance considering that, in some populations, partial deletions were shown to favor the occurrence of complete deletions. 38,39 The majority of gr/gr deletion carriers belonged, as expected, to the P,Q,R branches in both patients and controls, supporting that the phenotypic variability of gr/gr deletion is independent of Y-chromosomal background in Europeans. 40 Interestingly, we found b2/b3 deletion only in the patient cohort (4/296; 1.3%) and only one carrier belonged to hgr N and thus had the constitutive b2/b3 deletion.…”

Male infertility: Pathogenesis and clinical diagnosis

“…a clear cut causative factor for spermatogenic impairment) in the next generation. 65,66 Mutation analysis of the AR gene…”

Molecular Characterization of Some Genetic Factors Controlling Spermatogenesis in Egyptian Patients with Male Infertility

“…The AZFc rearrangement analysis results were interpreted according to Table 2. [11][12][13][14] Detailed sequences of the all primers that used in molecular studies were given in Table 3.…”