Integrative Analysis of Whole-Genome and Transcriptomic Data Reveals Novel Variants in Differentially Expressed Long
Maria-Anna Kyrgiafini1, Maria Katsigianni1, Themistoklis Giannoulis2
1Laboratory of Genetics, Comparative and Evolutionary Biology, Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, Mezourlo, 41500 Larissa, Greece.
Non-Coding RNA
|January 23, 2025
Summary
This study identifies novel variants in long noncoding RNAs (lncRNAs) linked to asthenozoospermia, a cause of male infertility. These genetic changes impact lncRNA structure and interactions, offering new insights into sperm motility disorders.
Area of Science:
- Genetics
- Reproductive Biology
- Bioinformatics
Background:
- Asthenozoospermia, characterized by reduced sperm motility, is a primary cause of male infertility.
- Long noncoding RNAs (lncRNAs) are increasingly recognized for their crucial roles in spermatogenesis and sperm function.
- While coding regions are studied, the role of noncoding regions in asthenozoospermia remains less understood.
Purpose of the Study:
- To identify and prioritize genetic variants within differentially expressed (DE) long noncoding RNAs (lncRNAs) exclusively found in asthenozoospermic men.
- To investigate the functional impact of these variants on lncRNA structure and lncRNA-miRNA-mRNA interactions.
- To provide a more holistic understanding of the genetic underpinnings of asthenozoospermia by focusing on noncoding regions.
Main Methods:
- Whole-genome sequencing (WGS) and RNA-sequencing (RNA-seq) were performed on samples from asthenozoospermic and normozoospermic individuals.
- Bioinformatics analyses were used to map unique variants to DE lncRNAs and predict their functional impact.
- Computational tools assessed the structural effects of variants and their influence on lncRNA-miRNA interactions, complemented by Gene Ontology and KEGG pathway analyses.
Main Results:
- 4173 unique variants were identified within 258 DE lncRNAs.
- Five variants in five lncRNAs affected lncRNA structure, and 20 variants in 17 lncRNAs were predicted to disrupt miRNA-lncRNA interactions.
- Enriched pathways included Wnt signaling, phosphatase binding, and cell proliferation, all relevant to reproductive health.
Conclusions:
- Specific variants in differentially expressed lncRNAs are identified as potential contributors to asthenozoospermia.
- This research highlights the significance of noncoding RNA variants in male infertility.
- The findings offer valuable insights and a foundation for future investigations into the role of noncoding RNAs in male reproductive health using whole-genome sequencing data.
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