Computational Analysis of the Potential Impact of MTC Complex Missenses SNPs Associated with Male Infertility.

Autor: Harmak H; Laboratory of Genomics and Human Genetics, 1 Place Louis Pasteur, Institut Pasteur du Maroc, Casablanca, Morocco.; Laboratory of Physiopathology, Molecular Genetics and Biotechnology, Department of Biology, Faculty of Sciences Ain Chock, Hassan II University, Casablanca, Morocco., Charoute H; Research Unit of Epidemiology, Biostatistics and Bioinformatics, Institut Pasteur du Maroc, Casablanca, Morocco., Redouane S; Laboratory of Genomics and Human Genetics, 1 Place Louis Pasteur, Institut Pasteur du Maroc, Casablanca, Morocco., Filali OA; Laboratory of Physiopathology, Molecular Genetics and Biotechnology, Department of Biology, Faculty of Sciences Ain Chock, Hassan II University, Casablanca, Morocco., Barakat A; Laboratory of Genomics and Human Genetics, 1 Place Louis Pasteur, Institut Pasteur du Maroc, Casablanca, Morocco., Rouba H; Laboratory of Genomics and Human Genetics, 1 Place Louis Pasteur, Institut Pasteur du Maroc, Casablanca, Morocco.
Jazyk: angličtina
Zdroj: BioMed research international [Biomed Res Int] 2022 Mar 18; Vol. 2022, pp. 1664825. Date of Electronic Publication: 2022 Mar 18 (Print Publication: 2022).
DOI: 10.1155/2022/1664825
Abstrakt: Meiotic chromosomes endure rapid prophase movements that ease the formation of interhomologue recombination intermediates that drive synapsis, crossing over, and segregation process. To generate these fast moves, the meiotic telomere complex (MTC) enables telomere-inner nuclear membrane attachment during meiotic prophase I and transfers cytoskeletal signals via another complex: the LINC complex. Furthermore, disruption or mutations of any of the MTC genes (TERB1, TERB2, and MAJIN) alters telomere association with the nuclear envelope leading to impairment of homologous pairing and synapsis, a meiotic arrest, and consequently to male infertility. To decipher the effect of TERB1, TERB2, and MAJIN missense mutations on protein structure, stability, and function, different bioinformatic tools were used in this study including VEP, Mutabind2, Haddock, Prodigy, Ligplot, ConSurf, DUET and MusiteDeep. In total, thirty mutations were predicted to be deleterious using VEP web server: seventeen for TERB1, eleven for TERB2, and two for MAJIN. All these single nucleotide polymorphisms were further analyzed and only 11 SNPs (W8R, G25R, P649A, I624T, C618R, F607V, S604G, C592Y, C592R, G187W, and R53C) were found to be the most damaging by at least six software tools and exert deleterious effect on the TERB1, TERB2, and MAJIN protein structures and likely functions. They revealed high conservation, less stability, and having a role in posttranslational modifications. This in silico approach provides information to gain further insights about variants that might affect stability, change binding affinity, and edit protein-protein interactions to facilitate their identification and functional characterization associated with male infertility.
Competing Interests: The authors declare that they have no conflicts of interest.
(Copyright © 2022 Houda Harmak et al.)
Databáze: MEDLINE
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