Genome Instability in Azoospermic Men Shows Association of Impaired DNA Recombination Repair with Post-Translational Hyper-Sumoylation

  • Baiba Alkšere (Speaker)
  • Puzuka, A. (Co-author)
  • Lazovska, M. (Co-author)
  • Ninela Vainselbauma (Co-author)
  • Janis Kristaps Vasilonoks (Co-author)
  • Elvita Penka (Co-author)
  • Violeta Fodina (Co-author)
  • Juris Erenpreiss (Co-author)

Activity: Talk or presentation types › Poster presentation

Description

Male infertility is a multifactorial pathology accounting for 40-50% of all infertility cases. The recent emergence of next generation sequencing (NGS) offers an opportunity to analyze many genes at once. Gene Set Enrichment Analysis (GSEA) analyzes gene networks sharing common regulation or biological function. There is still a lack of reports on whole exome sequencing (WES) implementation with gene network analysis in male infertility research. . WES was performed on 21 non-obstructive azoospermia patients with normal karyotype and excluded Y chromosome microdeletions. A gene set of previously described (n=140)1 and novel candidate genes (n=10)2,3,4,5 of azoospermia was compiled. Samples were sequenced using the Twist Comprehensive Exome Panel and analyzed with the Illumina’s Variant Interpreter. P and LP variants were confirmed by Sanger sequencing. Genetic burden test was performed with TRAPD. P value 50% of samples. Over-representation analysis with pathway based set of genes with high variant burden demonstrated 26 pathways, half of the pathways (13) being involved in spermatogenesis, especially sumoylation (4). Over-representation analysis with protein complex-based sets obtained 14 sets, all involved in DNA repair and genomic integrity. STRING analysis identified two gene clusters: 1) DNA binding/condensation and repair; 2) Ribosome biosynthesis and gene expression processes.. Increased loss of function variant burden and sumoylation may have critical significance in spermatogenesis. Sperm motility impairment is associated with upregulation of sumoylation. These parameters (increased LoF variant burden and the level of sumoylation (SUMO-1)) may be used for focused diagnosis and counselling in non-obstructive azoospermia patients.
Period29 Mar 2023
Event titleRSU International Research Conference 2023: Knowledge for Use in Practice
Event typeConference
OrganiserRīga Stradiņš University
LocationRiga, LatviaShow on map
Degree of RecognitionInternational

Related content