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Drosophila Model for the Analysis of Genesis of LIM-kinase 1-Dependent Williams-Beuren Syndrome Cognitive Phenotypes: INDELs, Transposable Elements of the Tc1/Mariner Superfamily and MicroRNAs
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SYSNO ASEP 0485553 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Drosophila Model for the Analysis of Genesis of LIM-kinase 1-Dependent Williams-Beuren Syndrome Cognitive Phenotypes: INDELs, Transposable Elements of the Tc1/Mariner Superfamily and MicroRNAs Author(s) Savvateeva-Popova, E.V. (RU)
Zhuravlev, A.V. (RU)
Brázda, Václav (BFU-R) RID, ORCID
Zakharov, G.A. (RU)
Kaminskaya, A.N. (RU)
Medvedeva, A.V. (RU)
Nikitina, E. (RU)
Tokmatcheva, E.V. (RU)
Dolgaya, J.F. (RU)
Kulikova, D.A. (RU)
Zatsepina, O. (RU)
Funikov, S.Y. (RU)
Ryazansky, S.S. (RU)
Evgen'ev, Michail B. (RU)Number of authors 14 Article number 123 Source Title Frontiers in genetics. - : Frontiers Media - ISSN 1664-8021
Roč. 8, SEP2017 (2017)Number of pages 13 s. Publication form Online - E Language eng - English Country CH - Switzerland Keywords b dna conformations ; swiss-model ; copy number ; polytene chromosomes Subject RIV EB - Genetics ; Molecular Biology OECD category Biochemistry and molecular biology Institutional support BFU-R - RVO:68081707 UT WOS 000411447200003 DOI https://doi.org/10.3389/fgene.2017.00123 Annotation Genomic disorders, the syndromes with multiple manifestations, may occur sporadically due to unequal recombination in chromosomal regions with specific architecture. Therefore, each patient may carry an individual structural variant of DNA sequence (SV) with small insertions and deletions (INDELs) sometimes less than 10 bp. The transposable elements of the Tc1/mariner superfamily are often associated with hotspots for homologous recombination involved in human genetic disorders, such as Williams Beuren Syndromes (WBS) with LIM-kinase 1-dependent cognitive defects. The Drosophila melanogaster mutant agn(ts3) has unusual architecture of the agnostic locus harboring LIMK1: it is a hotspot of chromosome breaks, ectopic contacts, underreplication, and recombination. Here, we present the analysis of LIMK1-containing locus sequencing data in agn(ts3) and three D. melanogaster wild-type strains-Canton-S, Berlin, and Oregon-R. We found multiple strain-specific SVs, namely, single base changes and small INDEls. The specific feature of agn(ts3) is 28 bp A/T-rich insertion in intron 1 of LIMK1 and the insertion of mobile S-element from Tc1/mariner superfamily residing similar to 460 bp downstream LIMK1 3'UTR. Neither of SVs leads to amino acid substitutions in agn(ts3) LIMK1. However, they apparently affect the nucleosome distribution, non-canonical DNA structure formation and transcriptional factors binding. Interestingly, the overall expression of miRNAs including the biomarkers for human neurological diseases, is drastically reduced in agn(ts3) relative to the wild-type strains. Thus, LIMK1 DNA structure per se, as well as the pronounced changes in total miRNAs profile, probably lead to LIMK1 dysregulation and complex behavioral dysfunctions observed in agn(ts3) making this mutant a simple plausible Drosophila model for WBS. Workplace Institute of Biophysics Contact Jana Poláková, polakova@ibp.cz, Tel.: 541 517 244 Year of Publishing 2018
Počet záznamů: 1