Organizational and functional status of the Y-linked genes and loci in the infertile patients having normal spermiogram.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Genes, Y-Linked/*genetics ; Genetic Loci/*genetics ; Infertility, Male/*genetics; Adult ; Azoospermia/genetics ; DNA Copy Number Variations/genetics ; Deleted in Azoospermia 1 Protein ; Gene Deletion ; Gene Dosage/genetics ; Humans ; Infertility, Male/metabolism ; Infertility, Male/physiopathology ; Male ; Polymorphism, Single Nucleotide/genetics ; Proteins/genetics ; RNA-Binding Proteins/genetics

Male fertility is an orchestrated interplay of loci on the Y chromosome with a number of genes from across the other chromosomes. In this context, micro-deletions in the Y chromosome have been correlated with spermatogenic failure often leading to infertility. However, causes of infertility in the patients with the normal spermiogram have remained unclear and therefore pose another level of challenge. In the present study, we analyzed 64 STSs, studied different Y-linked genes and loci and conducted single nucleotide variant (SNV) analyses in 31 infertile males with normal spermiogram along with 67 normal fertile males (NFMs) to gain an insight into the organization of their Y chromosome. Further, employing quantitative real-time PCR (qPCR), we studied copy number variation of DYZ1 arrays and three genes and mutational status of SRY by direct sequence analyses. STS analyses of the AZFa, b and c regions in these patients showed known and new mutations. Further, copies of DAZ and BPY2 in the patients were found to be affected (p < 0.001) compared to those in NFMs. All the patients had normal copy number of the SRY however its sequence analysis (in silico) showed mutations in eight patients. In four of these eight patients, SRY mutations resulted into truncated proteins. Similarly, DYZ1 analysis showed micro-deletions and it's much reduced copy number (p < 0.001) as compared to those in NFMs. Present study in males with unexplained infertility revealed deletions similar to those observed in oligospermic and azoospermic patients. Thus, there are some common but still unknown factors underlying infertility in these patients irrespective of their spermatogenic status. This work is envisaged to augment DNA diagnosis, proving beneficial in the context of in vitro fertilization (IVF) and genetic counselling.

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0 (BPY2 protein, human)
0 (DAZ1 protein, human)
0 (Deleted in Azoospermia 1 Protein)
0 (Proteins)
0 (RNA-Binding Proteins)

Date Created: 20120731 Date Completed: 20121128 Latest Revision: 20211021

20231215

PMC3402420

10.1371/journal.pone.0041488

22844483