vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ21.054vavilov-3105Research ArticleГЕНЕТИКА ЖИВОТНЫХANIMAL GENETICSВлияние родительского происхождения аллелей на пространственную организацию хромосом и поведение на модели синдрома Вильямса–Бойерна на дрозофилеParent-of-origin effects on nuclear chromatin organization and behavior in a Drosophila model for Williams–Beuren Syndromehttps://orcid.org/0000-0001-7989-8746МедведеваА. В.MedvedevaA. V.

Санкт-Петербург

St. Petersburg

https://orcid.org/0000-0002-2864-9894ТокмачеваЕ. В.TokmatchevaE. V.

Санкт-Петербург

St. Petersburg

КаминскаяА. Н.KaminskayaA. N.

Москва

Moscow

https://orcid.org/0000-0002-7785-7091ВасильеваС. А.VasilevaS. A.

Санкт-Петербург

St. Petersburg

https://orcid.org/0000-0003-1897-8392НикитинаЕ. А.NikitinaE. A.

Санкт-Петербург

St. Petersburg

https://orcid.org/0000-0003-2673-4283ЖуравлевА. В.ZhuravlevA. V.

Санкт-Петербург

St. Petersburg

https://orcid.org/0000-0003-4850-3777ЗахаровГ. А.ZakharovG. A.

Санкт-Петербург

St. Petersburg

https://orcid.org/0000-0001-5982-941XЗацепинаО. Г.ZatsepinaO. G.

Москва

Moscow

https://orcid.org/0000-0002-6925-4370Савватеева-ПоповаЕ. В.Savvateeva-PopovaE. V.

Санкт-Петербург

St. Petersburg

esavvateeva@mail.ruИнститут физиологии им. И.П. Павлова Российской академии наукРоссияPavlov Institute of Physiology of the Russian Academy of SciencesRussian FederationИнститут биоорганической химии Российской академии наукРоссияInstitute of Bioorganic Chemistry of the Russian Academy of SciencesRussian FederationИнститут физиологии им. И.П. Павлова Российской академии наук; Российский государственный педагогический университет им. А.И. ГерценаРоссияPavlov Institute of Physiology of the Russian Academy of Sciences; Herzen State Pedagogical University of RussiaRussian FederationИнститут молекулярной биологии им. В.А. Энгельгардта Российской академии наукРоссияEngelhardt Institute of Molecular Biology of the Russian Academy of SciencesRussian Federation202109092021255472485Copyright © Медведева А.В., Токмачева Е.В., Каминская А.Н., Васильева С.А., Никитина Е.А., Журавлев А.В., Захаров Г.А., Зацепина О.Г., Савватеева-Попова Е.В., 20212021Медведева А.В., Токмачева Е.В., Каминская А.Н., Васильева С.А., Никитина Е.А., Журавлев А.В., Захаров Г.А., Зацепина О.Г., Савватеева-Попова Е.В.Medvedeva A.V., Tokmatcheva E.V., Kaminskaya A.N., Vasileva S.A., Nikitina E.A., Zhuravlev A.V., Zakharov G.A., Zatsepina O.G., Savvateeva-Popova E.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/3105

Прогноз развития нейропсихиатрических заболеваний требует учитывать родительское п хождение аллелей как существенный фактор предрасположенности у потомства. Родительское наследование определяет 3D организацию хромосом в ядре нервных клеток, в том числе за счет эпигенетического влияния микро-РНК генеративных клеток родителей. Кроме того, когнитивные нейропатологии у родителей зависят от двух процессов – обучения и забывания, или стирания памяти. Эти процессы независимы и контролируются разными сигнальными каскадами: обучение – цАМФ-зависимым, забывание – каскадом ремоделирования актина: малая ГТФаза Rac1 – LIMK1 (LIM-kinase 1). Для понимания становления нейропатологии человека необходимо привлечение простых модельных объектов. Нами создана модель синдрома Вильямса–Бойерна на дрозофиле с мутационным повреждением гена dlimk1 – agnostic (agnts3), кодирующего ключевой фермент ремоделирования актина LIMK1. У agnts3 повышена частота формирования негомологичных контактов в специфических районах интеркалярного гетерохроматина, резко нарушены способность к обучению, формированию памяти и локомоция. У реципрокных гибридов между agnts3 и линией дикого типа Berlin частота эктопических контактов, сформированных дисками политенных хромосом, зависит от направления скрещивания, воспроизводя либо отцовские, либо материнские свойства. Биоинформационный анализ показывает, что частота эктопических контактов между X:11AB и другими районами Х хромосомы обусловлена присутствием короткого (~30 п. н.) фрагмента ДНК, частично гомологичного участку 372 п. н. сателлитной ДНК. Гибриды, имея одинаковую способность к обучению в парадигме условно-рефлекторного подавления ухаживания, проявляют патроклинный характер наследования среднесрочной памяти. Это может быть связано с уровнем экспрессии миР-794. Параметры локомоторной активности проявляют гетерозис. По-видимому, локус agnts3 осуществляет трансрегуляцию пространственной организации ядра, тем самым влияя на количественные признаки (поведение).

Prognosis of neuropsychiatric disorders in progeny requires consideration of individual (1) parent-of-origin effects (POEs) relying on (2) the nerve cell nuclear 3D chromatin architecture and (3) impact of parent-specific miRNAs. Additionally, the shaping of cognitive phenotypes in parents depends on both learning acquisition and forgetting, or memory erasure. These processes are independent and controlled by different signal cascades: the first is cAMPdependent, the second relies on actin remodeling by small GTPase Rac1 – LIMK1 (LIM-kinase 1). Simple experimental model systems such as Drosophila help probe the causes and consequences leading to human neurocognitive pathologies. Recently, we have developed a Drosophila model for Williams–Beuren Syndrome (WBS): a mutant agnts3 of the agnostic locus (X:11AB) harboring the dlimk1 gene. The agnts3 mutation drastically increases the frequency of ectopic contacts (FEC) in specific regions of intercalary heterochromatin, suppresses learning/memory and affects locomotion. As is shown in this study, the polytene X chromosome bands in reciprocal hybrids between agnts3 and the wild type strain Berlin are heterogeneous in modes of FEC regulation depending either on maternal or paternal gene origin. Bioinformatic analysis reveals that FEC between X:11AB and the other X chromosome bands correlates with the occurrence of short (~30 bp) identical DNA fragments partly homologous to Drosophila 372-bp satellite DNA repeat. Although learning acquisition in a conditioned courtship suppression paradigm is similar in hybrids, the middle-term memory formation shows patroclinic inheritance. Seemingly, this depends on changes in miR-974 expression. Several parameters of locomotion demonstrate heterosis. Our data indicate that the agnts3 locus is capable of trans-regulating gene activity via POEs on the chromatin nuclear organization, thereby affecting behavior.

эффект родительского происхождения аллелей3D организация ядраэктопические контакты хромосомLIM-киназа 1 (LIMK1)актинмикро-РНКобучениеформирование памятилокомоцияPOE (parent-of-origin effects)3D nuclear architecturechromatin ectopic contactsLIM-kinase 1 (LIMK1)actinmir-RNAlearning acquisitionmemory formationlocomotionThis work was supported by the Russian Foundation for Basic Research 20-015-00300 А (to EVSP) and Program of Basic Scientific Research of State Academies for 2013–2020, 47GP, section 63. We would like to thank Michail B. Evgen’ev from Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia for the suggestion of analysis of molecular and behavioral manifestations in reciprocal hybrids, Sergey Funikov from the same Institute and Sergei S. Ryazansky from the Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russia for performing miRNAs Bioinformatic Analysis.ReferencesBelyaeva E.S., Zhimulev I.F., Volkova E.I., Alekseyenko A.A., Moshkin Y.M., Koryakov D.E. Su(UR)ES: a gene suppressing DNA underreplication in intercalary and pericentric heterochromatin of Drosophila melanogaster polytene chromosomes. Proc. Natl. Acad. Sci. USA. 1998;95(13):7532-7537. DOI 10.1073/pnas.95.13.7532.Belyaeva E.S., Zhimulev I.F., Volkova E.I., Alekseyenko A.A., Moshkin Y.M., Koryakov D.E. Su(UR)ES: a gene suppressing DNA underreplication in intercalary and pericentric heterochromatin of Drosophila melanogaster polytene chromosomes. Proc. Natl. Acad. Sci. USA. 1998;95(13):7532-7537. DOI 10.1073/pnas.95.13.7532.Belyakin S.N., Christophides G.K., Alekseyenko A.A., Kriventseva E.V., Belyaeva E.S., Nanayev R.A., Makunin I.V., Kafatos F.C., Zhimulev I.F. Genomic analysis of Drosophila chromosome underreplication reveals a link between replication control and transcriptional territories. Proc. Natl. Acad. Sci. USA. 2005;102(23):8269-8274. DOI 10.1073/pnas.0502702102.Belyakin S.N., Christophides G.K., Alekseyenko A.A., Kriventseva E.V., Belyaeva E.S., Nanayev R.A., Makunin I.V., Kafatos F.C., Zhimulev I.F. Genomic analysis of Drosophila chromosome underreplication reveals a link between replication control and transcriptional territories. Proc. Natl. Acad. Sci. USA. 2005;102(23):8269-8274. DOI 10.1073/pnas.0502702102.Bourassa M.W., Ratan R.R. The interplay between microRNAs and histone deacetylases in neurological diseases. Neurochem. Int. 2014; 77:33-39. DOI 10.1016/j.neuint.2014.03.012.Bourassa M.W., Ratan R.R. The interplay between microRNAs and histone deacetylases in neurological diseases. Neurochem. Int. 2014; 77:33-39. DOI 10.1016/j.neuint.2014.03.012.Busto G.U., Guven-Ozkan T., Fulga T.A., Van Vactor D., Davis R.L. microRNAs that promote or inhibit memory formation in Drosophila melanogaster. Genetics. 2015;200(2):569-580. DOI 10.1534/genetics.114.169623.Busto G.U., Guven-Ozkan T., Fulga T.A., Van Vactor D., Davis R.L. microRNAs that promote or inhibit memory formation in Drosophila melanogaster. Genetics. 2015;200(2):569-580. DOI 10.1534/genetics.114.169623.Collette J.C., Chen X.N., Mills D.L., Galaburda A.M., Reiss A.L., Bellugi U., Korenberg J.R. William’s syndrome: gene expression is related to parental origin and regional coordinate control. J. Hum. Genet. 2009;54(4):193-198. DOI 10.1038/jhg.2009.5.Collette J.C., Chen X.N., Mills D.L., Galaburda A.M., Reiss A.L., Bellugi U., Korenberg J.R. William’s syndrome: gene expression is related to parental origin and regional coordinate control. J. Hum. Genet. 2009;54(4):193-198. DOI 10.1038/jhg.2009.5.Davis R.L., Zhong Y. The biology of forgetting – a perspective. Neuron. 2017;95(3):490-503. DOI 10.1016/j.neuron.2017.05.039.Davis R.L., Zhong Y. The biology of forgetting – a perspective. Neuron. 2017;95(3):490-503. DOI 10.1016/j.neuron.2017.05.039.Dong X., Chen J., Li T., Zhang X., Zhang M., Song W., Zhao H., Lai J. Parent-of-origin-dependent nucleosome organization correlates with genomic imprinting in maize. Genome Res. 2018;28(7):1020-1028. DOI 10.1101/gr.230201.117.Dong X., Chen J., Li T., Zhang X., Zhang M., Song W., Zhao H., Lai J. Parent-of-origin-dependent nucleosome organization correlates with genomic imprinting in maize. Genome Res. 2018;28(7):1020-1028. DOI 10.1101/gr.230201.117.Eagen K.P., Hartl T.A., Kornberg R.D. Stable chromosome condensation revealed by chromosome conformation capture. Cell. 2015; 163(4):934-946.Eagen K.P., Hartl T.A., Kornberg R.D. Stable chromosome condensation revealed by chromosome conformation capture. Cell. 2015; 163(4):934-946.Guven-Ozkan T., Busto G.U., Schutte S.S., Cervantes-Sandoval I., O’Dowd D.K., Davis R.L. MiR-980 is a memory suppressor microRNA that regulates the autism-susceptibility gene A2bp1. Cell Rep. 2016;14(7):1698-1709. DOI 10.1016/j.celrep.2016.01.040.Guven-Ozkan T., Busto G.U., Schutte S.S., Cervantes-Sandoval I., O’Dowd D.K., Davis R.L. MiR-980 is a memory suppressor microRNA that regulates the autism-susceptibility gene A2bp1. Cell Rep. 2016;14(7):1698-1709. DOI 10.1016/j.celrep.2016.01.040.Iourov I.Y., Vorsanova S.G., Yurov Y.B. Molecular cytogenetics and cytogenomics of brain diseases. Curr. Genomics. 2008;9(7):452-465. DOI 10.2174/138920208786241216.Iourov I.Y., Vorsanova S.G., Yurov Y.B. Molecular cytogenetics and cytogenomics of brain diseases. Curr. Genomics. 2008;9(7):452-465. DOI 10.2174/138920208786241216.Iourov I.Y., Vorsanova S.G., Yurov Y.B. Pathway-based classification of genetic diseases. Mol. Cytogenet. 2019;12:4. DOI 10.1186/s13039-019-0418-4.Iourov I.Y., Vorsanova S.G., Yurov Y.B. Pathway-based classification of genetic diseases. Mol. Cytogenet. 2019;12:4. DOI 10.1186/s13039-019-0418-4.Ito S., Magalska A., Alcaraz-Iborra M., Lopez-Atalaya J.P., Rovira V., Contreras-Moreira B., Lipinski M., Olivares R., Martinez-Hernandez J., Ruszczycki B., Lujan R., Geijo-Barrientos E., Wilczynski G.M., Barco A. Loss of neuronal 3D chromatin organization causes transcriptional and behavioural deficits related to serotonergic dysfunction. Nat. Commun. 2014;5:4450. DOI 10.1038/ncomms5450.Ito S., Magalska A., Alcaraz-Iborra M., Lopez-Atalaya J.P., Rovira V., Contreras-Moreira B., Lipinski M., Olivares R., Martinez-Hernandez J., Ruszczycki B., Lujan R., Geijo-Barrientos E., Wilczynski G.M., Barco A. Loss of neuronal 3D chromatin organization causes transcriptional and behavioural deficits related to serotonergic dysfunction. Nat. Commun. 2014;5:4450. DOI 10.1038/ncomms5450.Jagannathan M., Warsinger-Pepe N., Watase G.J., Yamashita Y.M. Comparative analysis of satellite DNA in the Drosophila melanogaster species complex. G3 (Bethesda). 2017;7(2):693-704. DOI 10.1534/g3.116.035352.Jagannathan M., Warsinger-Pepe N., Watase G.J., Yamashita Y.M. Comparative analysis of satellite DNA in the Drosophila melanogaster species complex. G3 (Bethesda). 2017;7(2):693-704. DOI 10.1534/g3.116.035352.Kaiser-Rogers K., Rao K. Structural chromosome rearrangements. In: Gersen S.L., Keagle M.B. (Eds.). The Principles of Clinical Cytogenetics. Humana Press, Totowa, NJ., 2005;165-206. DOI 10.1385/1-59259-833-1:165.Kaiser-Rogers K., Rao K. Structural chromosome rearrangements. In: Gersen S.L., Keagle M.B. (Eds.). The Principles of Clinical Cytogenetics. Humana Press, Totowa, NJ., 2005;165-206. DOI 10.1385/1-59259-833-1:165.Kaminskaya A.N., Nikitina E.A., Medvedeva A.V., Gerasimenko M.S., Chernikova D.A., Savvateeva-Popova E.V. The influence of the limk1 gene polymorphism on learning acquisition and memory formation, pCREB distribution and aggregate formation in neuromuscular junctions in Drosophila melanogaster. Russ. J. Genet. 2015; 51(6):582-590. DOI 10.1134/S1022795415060071.Kaminskaya A.N., Nikitina E.A., Medvedeva A.V., Gerasimenko M.S., Chernikova D.A., Savvateeva-Popova E.V. The influence of the limk1 gene polymorphism on learning acquisition and memory formation, pCREB distribution and aggregate formation in neuromuscular junctions in Drosophila melanogaster. Russ. J. Genet. 2015; 51(6):582-590. DOI 10.1134/S1022795415060071.Kamyshev N.G., Iliadi K.G., Bragina J.V. Drosophila conditioned courtship: two ways of testing memory. Learn. Mem. 1999;6:1-20. DOI 10.1101/lm.6.1.1.Kamyshev N.G., Iliadi K.G., Bragina J.V. Drosophila conditioned courtship: two ways of testing memory. Learn. Mem. 1999;6:1-20. DOI 10.1101/lm.6.1.1.Kim S., Yu N.K., Shim K.W., Kim J.I., Kim H., Han D.H., Choi J.E., Lee S.W., Choi D.I., Kim M.W., Lee D.S., Lee K., Galjart N., Lee Y.S., Lee J.H., Kaang B.K. Remote memory and cortical synaptic plasticity require neuronal CCCTC-binding factor (CTCF). J. Neurosci. 2018;38(22):5042-5052. DOI 10.1523/JNEUROSCI.2738-17.2018.Kim S., Yu N.K., Shim K.W., Kim J.I., Kim H., Han D.H., Choi J.E., Lee S.W., Choi D.I., Kim M.W., Lee D.S., Lee K., Galjart N., Lee Y.S., Lee J.H., Kaang B.K. Remote memory and cortical synaptic plasticity require neuronal CCCTC-binding factor (CTCF). J. Neurosci. 2018;38(22):5042-5052. DOI 10.1523/JNEUROSCI.2738-17.2018.Klages-Mundt N.L., Kumar A., Zhang Y., Kapoor P., Shen X. The nature of actin-family proteins in chromatin-modifying complexes. Front. Genet. 2018;9:398. DOI 10.3389/fgene.2018.00398.Klages-Mundt N.L., Kumar A., Zhang Y., Kapoor P., Shen X. The nature of actin-family proteins in chromatin-modifying complexes. Front. Genet. 2018;9:398. DOI 10.3389/fgene.2018.00398.Kolesnikova T.D. Banding pattern of polytene chromosomes as a representation of universal principles of chromatin organization into topological domains. Biochemistry. (Mosc). 2018;83(4):338-349.Kolesnikova T.D. Banding pattern of polytene chromosomes as a representation of universal principles of chromatin organization into topological domains. Biochemistry. (Mosc). 2018;83(4):338-349.Kozomara A., Birgaoanu M., Griffiths-Jones S. miRBase: from microRNA sequences to function. Nucleic Acids Res. 2019;47(D1): D155-D162. DOI 10.1093/nar/gky1141.Kozomara A., Birgaoanu M., Griffiths-Jones S. miRBase: from microRNA sequences to function. Nucleic Acids Res. 2019;47(D1): D155-D162. DOI 10.1093/nar/gky1141.Li K.L., Zhang L., Yang X.M., Fang Q., Yin X.F., Wei H.M., Zhou T., Li Y.B., Chen X.L., Tang F., Li Y.H., Chang J.F., Li W., Sun F. Histone acetyltransferase CBP-related H3K23 acetylation contributes to courtship learning in Drosophila. BMC Dev. Biol. 2018; 18(1):20. DOI 10.1186/s12861-018-0179-z.Li K.L., Zhang L., Yang X.M., Fang Q., Yin X.F., Wei H.M., Zhou T., Li Y.B., Chen X.L., Tang F., Li Y.H., Chang J.F., Li W., Sun F. Histone acetyltransferase CBP-related H3K23 acetylation contributes to courtship learning in Drosophila. BMC Dev. Biol. 2018; 18(1):20. DOI 10.1186/s12861-018-0179-z.Liehr T. From human cytogenetics to human chromosomics. Int. J. Mol. Sci. 2019;20(4):826. DOI 10.3390/ijms20040826.Liehr T. From human cytogenetics to human chromosomics. Int. J. Mol. Sci. 2019;20(4):826. DOI 10.3390/ijms20040826.Liu L., Li Q.Z., Jin W., Lv H., Lin H. Revealing gene function and transcription relationship by reconstructing gene-level chromatin interaction. Comput. Struct. Biotechnol. J. 2019;17:195-205. DOI 10.1016/j.csbj.2019.01.011.Liu L., Li Q.Z., Jin W., Lv H., Lin H. Revealing gene function and transcription relationship by reconstructing gene-level chromatin interaction. Comput. Struct. Biotechnol. J. 2019;17:195-205. DOI 10.1016/j.csbj.2019.01.011.Lobashev M.E., Ponomarenko B.B., Polyanskaya G.G., Tsapygina R.I. The role of nervous system in the regulation of genetic and cytogenetic processes. Zh. Evol. Biokhim. Phiziol. 1973;9:398-405. (in Russian)Lobashev M.E., Ponomarenko B.B., Polyanskaya G.G., Tsapygina R.I. The role of nervous system in the regulation of genetic and cytogenetic processes. Zh. Evol. Biokhim. Phiziol. 1973;9:398-405. (in Russian)Medrano-Fernández A., Barco A. Nuclear organization and 3D chromatin architecture in cognition and neuropsychiatric disorders. Mol. Brain. 2016;9(1):83. DOI 10.1186/s13041-016-0263-x.Medrano-Fernández A., Barco A. Nuclear organization and 3D chromatin architecture in cognition and neuropsychiatric disorders. Mol. Brain. 2016;9(1):83. DOI 10.1186/s13041-016-0263-x.Medvedeva A., Zhuravlev A., Savvateeva-Popova E. LIMK1, the key enzyme of actin remodeling bridges spatial organization of nucleus and neural transmission: from heterochromatin via non-coding RNAs to complex behavior. In: Cytoskeleton: Cell Movement, Cytokinesis and Organelles Organization. Nova Science Publishers, Inc., 2010;1: 37-67.Medvedeva A., Zhuravlev A., Savvateeva-Popova E. LIMK1, the key enzyme of actin remodeling bridges spatial organization of nucleus and neural transmission: from heterochromatin via non-coding RNAs to complex behavior. In: Cytoskeleton: Cell Movement, Cytokinesis and Organelles Organization. Nova Science Publishers, Inc., 2010;1: 37-67.Menon D.U., Coarfa C., Xiao W., Gunaratne P.H., Meller V.H. siRNAs from an X-linked satellite repeat promote X-chromosome recognition in Drosophila melanogaster. Proc. Natl. Acad. Sci. USA. 2014; 111(46):16460-16465. DOI 10.1073/pnas.1410534111.Menon D.U., Coarfa C., Xiao W., Gunaratne P.H., Meller V.H. siRNAs from an X-linked satellite repeat promote X-chromosome recognition in Drosophila melanogaster. Proc. Natl. Acad. Sci. USA. 2014; 111(46):16460-16465. DOI 10.1073/pnas.1410534111.Mohammed J., Bortolamiol-Becet D., Flynt A.S., Gronau I., Siepel A., Lai E.C. Adaptive evolution of testis-specific, recently evolved, clustered miRNAs in Drosophila. RNA. 2014;20(8):1195-1209. DOI 10.1261/rna.044644.114.Mohammed J., Bortolamiol-Becet D., Flynt A.S., Gronau I., Siepel A., Lai E.C. Adaptive evolution of testis-specific, recently evolved, clustered miRNAs in Drosophila. RNA. 2014;20(8):1195-1209. DOI 10.1261/rna.044644.114.Nikitina E.A., Kaminskaya A.N., Molotkov D.A., Popov A.V., Savvateeva-Popova E.V. Effect of heat shock on courtship behavior, sound production, and learning in comparison with the brain content of LIMK1 in Drosophila melanogaster males with altered structure of the LIMK1 gene. J. Evol. Biochem. Physiol. 2014a;50(2):154-166. DOI 10.1134/S0022093014020082.Nikitina E.A., Kaminskaya A.N., Molotkov D.A., Popov A.V., Savvateeva-Popova E.V. Effect of heat shock on courtship behavior, sound production, and learning in comparison with the brain content of LIMK1 in Drosophila melanogaster males with altered structure of the LIMK1 gene. J. Evol. Biochem. Physiol. 2014a;50(2):154-166. DOI 10.1134/S0022093014020082.Nikitina E., Medvedeva A., Zakharov G., Savvateeva-Popova E. The Drosophila agnostic locus: involvement in the formation of cognitive defects in Williams Syndrome. Acta Naturae. 2014b;6(2): 53-61.Nikitina E., Medvedeva A., Zakharov G., Savvateeva-Popova E. The Drosophila agnostic locus: involvement in the formation of cognitive defects in Williams Syndrome. Acta Naturae. 2014b;6(2): 53-61.Nikitina E., Medvedeva A., Zakharov G., Savvateeva-Popova E. Williams syndrome as a model for elucidation of the pathway genes the brain – cognitive functions: genetics and epigenetics. Acta Naturae. 2014c;6(1):9-22.Nikitina E., Medvedeva A., Zakharov G., Savvateeva-Popova E. Williams syndrome as a model for elucidation of the pathway genes the brain – cognitive functions: genetics and epigenetics. Acta Naturae. 2014c;6(1):9-22.Nikitina E.A., Medvedeva A.V., Dolgaya Yu.F., Korochkin L.I., Pavlova G.V., Savvateeva-Popova E.V. Involvement of GDNF and LIMK1 and heat shock proteins in Drosophila learning and memory formation. J. Evol. Biochem. Physiol. 2012;48:529-539. DOI 10.1134/S0022093012050076.Nikitina E.A., Medvedeva A.V., Dolgaya Yu.F., Korochkin L.I., Pavlova G.V., Savvateeva-Popova E.V. Involvement of GDNF and LIMK1 and heat shock proteins in Drosophila learning and memory formation. J. Evol. Biochem. Physiol. 2012;48:529-539. DOI 10.1134/S0022093012050076.Peffer S., Cope K., Morano K. Unraveling protein misfolding diseases using model systems. Future Sci. OA. 2015;1(2). DOI 10.4155/fso.15.41.Peffer S., Cope K., Morano K. Unraveling protein misfolding diseases using model systems. Future Sci. OA. 2015;1(2). DOI 10.4155/fso.15.41.Pérez Jurado L.A., Peoples R., Kaplan P., Hamel B.C., Francke U. Molecular definition of the chromosome 7 deletion in Williams syndrome and parent-of-origin effects on growth. Am. J. Hum. Genet. 1996;59(4):781-792.Pérez Jurado L.A., Peoples R., Kaplan P., Hamel B.C., Francke U. Molecular definition of the chromosome 7 deletion in Williams syndrome and parent-of-origin effects on growth. Am. J. Hum. Genet. 1996;59(4):781-792.Qin H., Niu T., Zhao J. Identifying multi-omics causers and causal pathways for complex traits. Front. Genet. 2019;10:110. DOI 10.3389/fgene.2019.00110. PMID: 30847004. PMCID: PMC6393387.Qin H., Niu T., Zhao J. Identifying multi-omics causers and causal pathways for complex traits. Front. Genet. 2019;10:110. DOI 10.3389/fgene.2019.00110. PMID: 30847004. PMCID: PMC6393387.Quinlan A.R., Hall I.M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics. 2010;26(6):841-842. DOI 10.1093/bioinformatics/btq033.Quinlan A.R., Hall I.M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics. 2010;26(6):841-842. DOI 10.1093/bioinformatics/btq033.Robinson M.D., McCarthy D.J., Smyth G.K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2010;26(1):139-140. DOI 10.1093/bioinformatics/btp616.Robinson M.D., McCarthy D.J., Smyth G.K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2010;26(1):139-140. DOI 10.1093/bioinformatics/btp616.Savvateeva-Popova E.V., Zhuravlev A.V., Brázda V., Zakharov G.A., Kaminskaya A.N., Medvedeva A.V., Nikitina E.A., Tokmatcheva E.V., Dolgaya J.F., Kulikova D.A., Zatsepina O.G., Funikov S.Y., Ryazansky S.S., Evgen’ev M.B. 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. Front. Genet. 2017; 8:123. DOI 10.3389/fgene.2017.00123.Savvateeva-Popova E.V., Zhuravlev A.V., Brázda V., Zakharov G.A., Kaminskaya A.N., Medvedeva A.V., Nikitina E.A., Tokmatcheva E.V., Dolgaya J.F., Kulikova D.A., Zatsepina O.G., Funikov S.Y., Ryazansky S.S., Evgen’ev M.B. 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. Front. Genet. 2017; 8:123. DOI 10.3389/fgene.2017.00123.Schier A.F. The maternal-zygotic transition: death and birth of RNAs. Science. 2007;316(5823):406-407. DOI 10.1126/science.1140693. PMID: 17446392.Schier A.F. The maternal-zygotic transition: death and birth of RNAs. Science. 2007;316(5823):406-407. DOI 10.1126/science.1140693. PMID: 17446392.Sempere L.F., Sokol N.S., Dubrovsky E.B., Berger E.M., Ambros V. Temporal regulation of microRNA expression in Drosophila melanogaster mediated by hormonal signals and Broad-Complex gene activity. Dev. Biol. 2003;259(1):9-18. DOI 10.1016/s0012-1606(03)00208-2. PMID: 12812784.Sempere L.F., Sokol N.S., Dubrovsky E.B., Berger E.M., Ambros V. Temporal regulation of microRNA expression in Drosophila melanogaster mediated by hormonal signals and Broad-Complex gene activity. Dev. Biol. 2003;259(1):9-18. DOI 10.1016/s0012-1606(03)00208-2. PMID: 12812784.Smrt R.D., Zhao X. Epigenetic regulation of neuronal dendrite and dendritic spine development. Front. Biol. (Beijing). 2010;5(4):304-323. DOI 10.1007/s11515-010-0650-0.Smrt R.D., Zhao X. Epigenetic regulation of neuronal dendrite and dendritic spine development. Front. Biol. (Beijing). 2010;5(4):304-323. DOI 10.1007/s11515-010-0650-0.Soni K., Choudhary A., Patowary A., Singh A.R., Bhatia S., Sivasubbu S., Chandrasekaran S., Pillai B. miR-34 is maternally inherited in Drosophila melanogaster and Danio rerio. Nucleic Acids Res. 2013;41(8):4470-4480. DOI 10.1093/nar/gkt139.Soni K., Choudhary A., Patowary A., Singh A.R., Bhatia S., Sivasubbu S., Chandrasekaran S., Pillai B. miR-34 is maternally inherited in Drosophila melanogaster and Danio rerio. Nucleic Acids Res. 2013;41(8):4470-4480. DOI 10.1093/nar/gkt139.Tokmacheva E.V. The mitotic activity of the cells in the head neural ganglion in larvae of the Drosophila ts mutant with an altered capacity for learning and augmented calmodulin activation properties. Zh. Vyssh. Nerv. Deiat. Im. I.P. Pavlova. 1995;45(3):565-571. (in Russian)Tokmacheva E.V. The mitotic activity of the cells in the head neural ganglion in larvae of the Drosophila ts mutant with an altered capacity for learning and augmented calmodulin activation properties. Zh. Vyssh. Nerv. Deiat. Im. I.P. Pavlova. 1995;45(3):565-571. (in Russian)Vasiljeva S., Tokmacheva E., Medvedeva A., Ermilova A., Nikitina E., Shchegolev B., Surma S.V., Savvateeva-Popova E.V. Parent-of-origin effect in genetic instability of somatic brain’s cells of Drosophila and memory formation under normal and stress conditions. Tsitologiia. 2019;61(12):951-963. DOI 10.1134/S0041377119120071. (in Russian)Vasiljeva S., Tokmacheva E., Medvedeva A., Ermilova A., Nikitina E., Shchegolev B., Surma S.V., Savvateeva-Popova E.V. Parent-of-origin effect in genetic instability of somatic brain’s cells of Drosophila and memory formation under normal and stress conditions. Tsitologiia. 2019;61(12):951-963. DOI 10.1134/S0041377119120071. (in Russian)Waring G.L., Pollack J.C. Cloning and characterization of a dispersed, multicopy, X chromosome sequence in Drosophila melanogaster. Proc. Natl. Acad. Sci. USA. 1987;84(9):2843-2847. DOI 10.1073/pnas.84.9.2843.Waring G.L., Pollack J.C. Cloning and characterization of a dispersed, multicopy, X chromosome sequence in Drosophila melanogaster. Proc. Natl. Acad. Sci. USA. 1987;84(9):2843-2847. DOI 10.1073/pnas.84.9.2843.Wittkopp P.J., Haerum B.K., Clark A.G. Parent-of-origin effects on mRNA expression in Drosophila melanogaster not caused by genomic imprinting. Genetics. 2006;173(3):1817-1821. DOI 10.1534/genetics.105.054684.Wittkopp P.J., Haerum B.K., Clark A.G. Parent-of-origin effects on mRNA expression in Drosophila melanogaster not caused by genomic imprinting. Genetics. 2006;173(3):1817-1821. DOI 10.1534/genetics.105.054684.Zakharov G. Locotrack. https://github.com/GennadiyZakharov/loco track. 2017. (Accessed April 3, 2020).Zakharov G. Locotrack. https://github.com/GennadiyZakharov/loco track. 2017. (Accessed April 3, 2020).Zakharov G.A., Zhuravlev A.V., Payalina T.L., Kamyshov N.G., Savvateeva-Popova E.V. The effect of mutations of the kynurenine pathway of tryptophan metabolism on locomotor behavior and gene expression in glutamatergic and cholinergic systems of D. melanogaster. Russ. J. Genet. Appl. Res. 2012;2:197-204. DOI 10.1134/S2079059712020141.Zakharov G.A., Zhuravlev A.V., Payalina T.L., Kamyshov N.G., Savvateeva-Popova E.V. The effect of mutations of the kynurenine pathway of tryptophan metabolism on locomotor behavior and gene expression in glutamatergic and cholinergic systems of D. melanogaster. Russ. J. Genet. Appl. Res. 2012;2:197-204. DOI 10.1134/S2079059712020141.Zayats T., Johansson S., Haavik J. Expanding the toolbox of ADHD genetics. How can we make sense of parent of origin effects in ADHD and related behavioral phenotypes? Behav. Brain Funct. 2015;11(1):33. DOI 10.1186/s12993-015-0078-4.Zayats T., Johansson S., Haavik J. Expanding the toolbox of ADHD genetics. How can we make sense of parent of origin effects in ADHD and related behavioral phenotypes? Behav. Brain Funct. 2015;11(1):33. DOI 10.1186/s12993-015-0078-4.Zerbino D.R., Achuthan P., Akanni W., Amode M.R., Barrell D., Bhai J., Flicek P. Ensembl 2018. Nucleic Acids Res. 2018;46:D754-D761. DOI 10.1093/nar/gkx1098.Zerbino D.R., Achuthan P., Akanni W., Amode M.R., Barrell D., Bhai J., Flicek P. Ensembl 2018. Nucleic Acids Res. 2018;46:D754-D761. DOI 10.1093/nar/gkx1098.Zhuravlev A. Homology Segment Analysis. Available at: https://bitbucket.org/beneor/homology-segment-analysis/src/master/2019a. (Accessed September 3, 2019).Zhuravlev A. Homology Segment Analysis. Available at: https://bitbucket.org/beneor/homology-segment-analysis/src/master/2019a. (Accessed September 3, 2019).Zhuravlev A. Homology Segment Analysis protocol. protocols.io. 2019b. DOI 10.17504/protocols.io.bakyicxw.Zhuravlev A. Homology Segment Analysis protocol. protocols.io. 2019b. DOI 10.17504/protocols.io.bakyicxw.Zink F., Magnusdottir D.N., Magnusson O.T., Walker N.J., Morris T.J., Sigurdsson A., Halldorsson G.H., Gudjonsson S.A., Melsted P., Ingimundardottir H., Kristmundsdottir S., Alexandersson K.F., Helgadottir A., Gudmundsson J., Rafnar T., Jonsdottir I., Holm H., Eyjolfsson G.I., Sigurdardottir O., Olafsson I., Masson G., Gudbjartsson D.F., Thorsteinsdottir U., Halldorsson B.V., Stacey S.N., Stefansson K. Insights into imprinting from parent-of-origin phased methylomes and transcriptomes. Nat. Genet. 2018;50(11):15421552. DOI 10.1038/s41588-018-0232-7.Zink F., Magnusdottir D.N., Magnusson O.T., Walker N.J., Morris T.J., Sigurdsson A., Halldorsson G.H., Gudjonsson S.A., Melsted P., Ingimundardottir H., Kristmundsdottir S., Alexandersson K.F., Helgadottir A., Gudmundsson J., Rafnar T., Jonsdottir I., Holm H., Eyjolfsson G.I., Sigurdardottir O., Olafsson I., Masson G., Gudbjartsson D.F., Thorsteinsdottir U., Halldorsson B.V., Stacey S.N., Stefansson K. Insights into imprinting from parent-of-origin phased methylomes and transcriptomes. Nat. Genet. 2018;50(11):15421552. DOI 10.1038/s41588-018-0232-7.Zykova T.Y., Levitsky V.G., Belyaeva E.S., Zhimulev I.F. Polytene chromosomes – a portrait of functional organization of the Drosophila genome. Curr. Genomics. 2018;9(3):179-191. DOI 10.2174/1389202918666171016123830.Zykova T.Y., Levitsky V.G., Belyaeva E.S., Zhimulev I.F. Polytene chromosomes – a portrait of functional organization of the Drosophila genome. Curr. Genomics. 2018;9(3):179-191. DOI 10.2174/1389202918666171016123830.

The authors declare that there are no conflicts of interest present.