Exploring the Potential of Exome Sequencing in Idiopathic Azoospermia : A Genetic Burden and Network Analysis Study

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dc.contributor.authorAlkšere, Baiba
dc.contributor.authorPuzuka, Agrita
dc.contributor.authorLazovska, Marija
dc.contributor.authorVainselbaum, Ninel Miriam
dc.contributor.authorVasilonoks, Janis Kristaps
dc.contributor.authorPenka, Elvita
dc.contributor.authorFodina, Violeta
dc.contributor.authorĒrenpreiss, Juris
dc.contributor.institutionDepartment of Biology and Microbiology
dc.contributor.institutionScientific Laboratory of Molecular Genetics
dc.date.accessioned2023-09-01T21:02:24Z
dc.date.available2023-09-01T21:02:24Z
dc.date.issued2023-08-17
dc.descriptionPublisher Copyright: © 2023 Baiba Alkšere et al.
dc.description.abstractThe purpose of this study was to investigate the linkage of the association of azoospermia phenotype with genetic alterations, involved in genome instability. Male infertility is a multifactorial pathology, and genetic alterations might be the underlying factors in majority of cases of severe male infertility. The recent emergence of next-generation sequencing offers an opportunity to analyze many genes and their interactions at once, and whole-exome sequencing (WES) together with whole-genome sequencing (WGS) was recently suggested for implementation of diagnosis workup in severe infertility cases. However, the reports on WES in conjunction with burden tests and gene network analysis are scarce or lacking in cases of severe male infertility. WES was performed on 21 nonobstructive azoospermia patients. DNA samples were sequenced using the Twist Comprehensive Exome Panel. Genetic burden test was performed with Testing Rare vAriants using Public Data. Protein interactions were investigated with ConsensusPathDB and Cytoscape. For single nucleotide variants and copy number variations (CNV) analysis, samples were analyzed with the Illumina's BaseSpace Variant Interpreter. Genetic variant burden was found elevated in 1,473 genes out of 30,000 known testis expressed genes. Three hundred and two genes with increased loss-of-function (LoF) variant set were present in more than one sample. Overrepresentation analysis with pathway-based set of genes with high variant burden demonstrated 26 pathways. Overrepresentation analysis with protein complex-based gene sets obtained 14 sets, showing the involvement in cell proliferation and DNA repair. Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) network analysis with Cytoscape identified two clusters: (1) genes, involved in DNA binding/condensation and repair processes and (2) genes with the role in ribosome biosynthesis and gene expression processes. Increased loss of function germline variant burden and sumoylation may have critical significance in spermatogenesis. These parameters may be used for focused diagnosis in nonobstructive azoospermia patients. This may have both general significance for the decreased organism functionality but in particular is critical in spermatogenesis.en
dc.description.statusPeer reviewed
dc.format.extent12
dc.format.extent1066427
dc.identifier.citationAlkšere, B, Puzuka, A, Lazovska, M, Vainselbaum, N M, Vasilonoks, J K, Penka, E, Fodina, V & Ērenpreiss, J 2023, 'Exploring the Potential of Exome Sequencing in Idiopathic Azoospermia : A Genetic Burden and Network Analysis Study', Andrologia, vol. 2023, 3107568. https://doi.org/10.1155/2023/3107568
dc.identifier.doi10.1155/2023/3107568
dc.identifier.issn0303-4569
dc.identifier.otherMendeley: 1eddb68e-1731-3595-9089-001cc8654cc9
dc.identifier.urihttps://dspace.rsu.lv/jspui/handle/123456789/14874
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85170435680&partnerID=8YFLogxK
dc.language.isoeng
dc.relation.ispartofAndrologia
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subject3.1 Basic medicine
dc.subject1.1. Scientific article indexed in Web of Science and/or Scopus database
dc.titleExploring the Potential of Exome Sequencing in Idiopathic Azoospermia : A Genetic Burden and Network Analysis Studyen
dc.type/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article

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