Towards a Comprehensive Catalog of Human Genes Associated with Main Forms of Pathozoospermia and its Functional Annotation

Poster (download) Elena V. Ignatieva1, Alexander V. Osadchuk2, Maxim A Kleshev3, Ludmila V. Osadchuk41The Federal Research Center Institute of Cytology and Genetics, SB RAS, eignat@bionet.nsc.ru2The Federal Research Center Institute of Cytology and Genetics, SB RAS, osadchuk@bionet.nsc.ru3The Federal Research Center Institute of Cytology and Genetics, SB RAS, max82cll@bionet.nsc.ru4The Federal Research Center Institute of Cytology and Genetics, SB RAS, losadch@bionet.nsc.ru The genetic causes of the global decline in male fertility is among the hot spots of scientific research in reproductive genetics. The most common way to evaluate male fertility in clinical trials is to determine the quality of the ejaculate. A pathological condition characterized by lower quality indicators of the ejaculate compared to the norm and leading to impaired fertility is called pathozoospermia. Pathozoospermia is a syndrome that occurs in many diseases and can be caused by many factors, including genetic ones. To systematize information about genes associated with main forms of pathozoospermia, we created a catalog of such genes and analyzed their functional characteristics. On the basis of a manual analysis of scientific publications we collected data on 70 genes harboring more than one hundred allelic variants associated with pathozoospermia. Gene ontology enrichment analysis revealed that genes were significantly associated with spermatogenesis and male gamete generation. In addition it was found that genes from the catalog were associated with more than seventy human diseases that were both reproductive system pathologies and others, such as Parkinson\’s and Alzheimer\’s diseases as well as various cancer types.

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Reconstruction and Analysis of Regulatory Gene Networks Involving Human Genes Associated with Main Forms of Pathozoospermia

Poster (download) Elena V. Ignatieva1, Alexander V. Osadchuk2, Maxim A Kleshev3, Ludmila V. Osadchuk41The Federal Research Center Institute of Cytology and Genetics, SB RAS, eignat@bionet.nsc.ru2The Federal Research Center Institute of Cytology and Genetics, SB RAS, osadchuk@bionet.nsc.ru3The Federal Research Center Institute of Cytology and Genetics, SB RAS, max82cll@bionet.nsc.ru4The Federal Research Center Institute of Cytology and Genetics, SB RAS, losadch@bionet.nsc.ru The study of the molecular-genetic mechanisms predisposing to decline in male reproductive potential (spermatogenic failure) is an actual problem of reproductive biology. Most often in laboratory studies evaluating male fertility, a study of the quality of ejaculate is used. Thus, a pathological condition called pathozoospermia can be detected if the quality indicators of the ejaculate are decreased. Pathozoospermia can manifest itself in several distinct forms, may occur in many diseases and can be caused by many factors, including genetic ones. To reveal regulatory interactions between genes associated with pathozoospermia, we reconstructed gene regulatory network involving genes harboring allelic variants associated with pathozoospermia. Regulatory network comprised seven genes encoding transcription factors (TFs) for which a set of target genes were predicted by MoLoTool web-service. We identified three key regulatory transcription factors (WT1, AHR, NR0B1) that have the greatest number of target genes in the network. Genes encoding these factors can be considered as the most promising candidate genes for identifying genetic variants associated with pathozoospermia.

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