Human Molecular Genetics Advance Access originally published online on December 16, 2008
Human Molecular Genetics 2009 18(6):1122-1130; doi:10.1093/hmg/ddn427
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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
1 Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China 2 MOE Key Laboratory of Contemporary Anthropology and Center for Evolutionary Biology, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai 200433, China 3 CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China 4 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA 5 Department of Acute Infectious Diseases Prevention and Control, Jiangsu Centers for Disease Prevention and Control, Nanjing 210009, China
* To whom correspondence should be addressed. Tel: +86 2586862863; Fax: +86 2586662863; Email: xrwang{at}njmu.edu.cn
Received September 22, 2008; Revised November 17, 2008; Accepted December 10, 2008
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.