M. Pirkl, Joachim Büch, Georg Friedrich, Michael Böhm, Dan Turner, Olaf Degen, Rolf Kaiser, Thomas Lengauer
Even after three decades of antiretroviral therapy for HIV-1, therapy failure is a continual challenge. This is especially so, if the viral variant is a recombinant of subtypes. Thus, improved diagnosis of recombined subtypes can help with the selection of therapy. We are using a new implementation of the previously published computational method recco to detect de novo recombination of known subtypes, independent of and in addition to known circulating recombinant forms (CRFs). We detect an optimal path in a multiple alignment of viral reference sequences based on mutation calls and probable breakpoints for recombination. A tuning parameter is used to favor either mutation calls or breakpoints. Besides novel recombinants, our tool g2p-recco integrated in the geno2pheno web-service https://geno2pheno.org can successfully detect known recombinant events given only the full consensus references (without CRFs) of the involved subtypes with breakpoints. In addition, the tool can be applied to other viruses, i.e hepatitis E virus (HEV). In this fashion, we could also detect several previously unknown recombinations in HEV.
{"title":"Geno2pheno: Recombination detection for HIV-1 and HEV subtypes","authors":"M. Pirkl, Joachim Büch, Georg Friedrich, Michael Böhm, Dan Turner, Olaf Degen, Rolf Kaiser, Thomas Lengauer","doi":"10.1093/narmme/ugae003","DOIUrl":"https://doi.org/10.1093/narmme/ugae003","url":null,"abstract":"\u0000 Even after three decades of antiretroviral therapy for HIV-1, therapy failure is a continual challenge. This is especially so, if the viral variant is a recombinant of subtypes. Thus, improved diagnosis of recombined subtypes can help with the selection of therapy. We are using a new implementation of the previously published computational method recco to detect de novo recombination of known subtypes, independent of and in addition to known circulating recombinant forms (CRFs). We detect an optimal path in a multiple alignment of viral reference sequences based on mutation calls and probable breakpoints for recombination. A tuning parameter is used to favor either mutation calls or breakpoints. Besides novel recombinants, our tool g2p-recco integrated in the geno2pheno web-service https://geno2pheno.org can successfully detect known recombinant events given only the full consensus references (without CRFs) of the involved subtypes with breakpoints. In addition, the tool can be applied to other viruses, i.e hepatitis E virus (HEV). In this fashion, we could also detect several previously unknown recombinations in HEV.","PeriodicalId":516789,"journal":{"name":"NAR Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140496664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mathilde Guibert, Hélène Marty-Capelle, Anne Robert, Bruno Charpentier, S. Labialle
The Prader–Willi/Angelman syndrome (PWS/AS) locus is regulated by the epigenetic mechanism of parental genomic imprinting. This region holds two eutherian-specific, large tandem repeats of box C/D small nucleolar RNA (Snord) genes called SNORD115 and SNORD116, whose loss of paternal expression is key in the development of the PWS. Snords represent an ancient class of noncoding RNAs that typically direct the 2′-O-methylation of specific nucleotides of ribosomal RNAs. However, Snord115 and Snord116 belong to the large class of orphan Snords whose functions remain unclear. The constraints that generated and maintained their unusual genetic organization for mammalian genomes have been poorly addressed to date. Here, a comparative analysis of the evolutionary history of both tandem repeats reveals that several genetic events affected them concomitantly, including copy gains and losses between species, emergence of gene subfamilies in catarrhines or partial tandem duplication in rats. Several indications suggest that parental genomic imprinting orchestrated this coordination of events, adding a new effect on mammalian genome structure and evolution to its roles in gene dosage, meiotic recombination and replication timing. Finally, our work provides a functional rationale for the existence of closely located tandem repeats of small RNA genes in mammalian genomes.
{"title":"Coordinated evolution of the SNORD115 and SNORD116 tandem repeats at the imprinted Prader–Willi/Angelman locus","authors":"Mathilde Guibert, Hélène Marty-Capelle, Anne Robert, Bruno Charpentier, S. Labialle","doi":"10.1093/narmme/ugad003","DOIUrl":"https://doi.org/10.1093/narmme/ugad003","url":null,"abstract":"\u0000 The Prader–Willi/Angelman syndrome (PWS/AS) locus is regulated by the epigenetic mechanism of parental genomic imprinting. This region holds two eutherian-specific, large tandem repeats of box C/D small nucleolar RNA (Snord) genes called SNORD115 and SNORD116, whose loss of paternal expression is key in the development of the PWS. Snords represent an ancient class of noncoding RNAs that typically direct the 2′-O-methylation of specific nucleotides of ribosomal RNAs. However, Snord115 and Snord116 belong to the large class of orphan Snords whose functions remain unclear. The constraints that generated and maintained their unusual genetic organization for mammalian genomes have been poorly addressed to date. Here, a comparative analysis of the evolutionary history of both tandem repeats reveals that several genetic events affected them concomitantly, including copy gains and losses between species, emergence of gene subfamilies in catarrhines or partial tandem duplication in rats. Several indications suggest that parental genomic imprinting orchestrated this coordination of events, adding a new effect on mammalian genome structure and evolution to its roles in gene dosage, meiotic recombination and replication timing. Finally, our work provides a functional rationale for the existence of closely located tandem repeats of small RNA genes in mammalian genomes.","PeriodicalId":516789,"journal":{"name":"NAR Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140518809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Introducing NAR Molecular Medicine, a new journal in the Nucleic Acids Research family","authors":"M. Spies","doi":"10.1093/narmme/ugad002","DOIUrl":"https://doi.org/10.1093/narmme/ugad002","url":null,"abstract":"","PeriodicalId":516789,"journal":{"name":"NAR Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139640830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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