{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T23:35:34Z","timestamp":1776468934881,"version":"3.51.2"},"reference-count":92,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T00:00:00Z","timestamp":1712534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The sheer number of gene variants and the extent of the observed clinical and molecular heterogeneity recorded in neuropsychiatric disorders (NPDs) could be due to the magnified downstream effects initiated by a smaller group of genomic higher-order alterations in response to endogenous or environmental stress. Chromosomal common fragile sites (CFS) are functionally linked with microRNAs, gene copy number variants (CNVs), sub-microscopic deletions and duplications of DNA, rare single-nucleotide variants (SNVs\/SNPs), and small insertions\/deletions (indels), as well as chromosomal translocations, gene duplications, altered methylation, microRNA and L1 transposon activity, and 3-D chromosomal topology characteristics. These genomic structural features have been linked with various NPDs in mostly isolated reports and have usually only been viewed as areas harboring potential candidate genes of interest. The suggestion to use a higher level entry point (the \u2018fragilome\u2019 and associated features) activated by a central mechanism (\u2018stress\u2019) for studying NPD genetics has the potential to unify the existing vast number of different observations in this field. This approach may explain the continuum of gene findings distributed between affected and unaffected individuals, the clustering of NPD phenotypes and overlapping comorbidities, the extensive clinical and molecular heterogeneity, and the association with certain other medical disorders.<\/jats:p>","DOI":"10.3390\/genes15040471","type":"journal-article","created":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T12:01:22Z","timestamp":1712577682000},"page":"471","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Unifying Hypothesis for the Genome Dynamics Proposed to Underlie Neuropsychiatric Phenotypes"],"prefix":"10.3390","volume":"15","author":[{"given":"George Sebastian","family":"Gericke","sequence":"first","affiliation":[{"name":"Faculty of Health Sciences, Prinshof Campus, University of Pretoria, Gezina 0031, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/wps.21034","article-title":"New insights from the last decade of research in psychiatric genetics: Discoveries, challenges, and clinical implications","volume":"22","author":"Andreassen","year":"2023","journal-title":"World Psychiatry"},{"key":"ref_2","unstructured":"(2024, February 10). iPSYCH. Available online: http:\/\/ipsych.au.dk."},{"key":"ref_3","unstructured":"(2024, February 10). Psychiatric Genomics Consortium (PGC). Available online: http:\/\/www.med.unc.edu\/pgc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1007\/s00239-019-09911-6","article-title":"An Evolutionary Perspective on the Impact of Genomic Copy Number Variation on Human Health","volume":"88","author":"Saitou","year":"2020","journal-title":"J. Mol. Evol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s13073-020-00734-5","article-title":"Translating insights from neuropsychiatric genetics and genomics for precision psychiatry","volume":"12","author":"Rees","year":"2020","journal-title":"Genome Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1101\/gr.116814.110","article-title":"What fraction of the human genome is functional?","volume":"21","author":"Ponting","year":"2011","journal-title":"Genome Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/s41398-021-01499-0","article-title":"Identification of inflammatory subgroups of schizophrenia and bipolar disorder patients with HERV-W ENV antigenemia by unsupervised cluster analysis","volume":"11","author":"Tamouza","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1016\/j.cell.2019.11.020","article-title":"Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders","volume":"179","author":"Lee","year":"2019","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/s41588-022-01057-4","article-title":"Genetic architecture of 11 major psychiatric disorders at biobehavioral, functional genomic and molecular genetic levels of analysis","volume":"54","author":"Grotzinger","year":"2022","journal-title":"Nat. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"The Brainstorm Consortium, Anttila, V., Bulik-Sullivan, B., Finucane, H.K., Walters, R.K., Bras, J., Duncan, L., Escott-Price, V., Falcone, G.J., and Gormley, P. (2018). Analysis of shared heritability in common disorders of the brain. Science, 360, eaap8757.","DOI":"10.1126\/science.aap8757"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1038\/mp.2012.105","article-title":"Why has it taken so long for biological psychiatry to develop clinical tests and what to do about it?","volume":"17","author":"Kapur","year":"2012","journal-title":"Mol. Psychiatry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1002\/wps.20999","article-title":"Incremental advances in psychiatric molecular genetics and nosology","volume":"21","author":"Kendler","year":"2022","journal-title":"World Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1176\/appi.ajp.2017.17030283","article-title":"Psychiatric Genomics: An Update and an Agenda","volume":"175","author":"Sullivan","year":"2018","journal-title":"Am. J. Psychiatry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1146\/annurev-biodatasci-092820-020354","article-title":"Integration of Multimodal Data for Deciphering Brain Disorders","volume":"4","author":"Chen","year":"2021","journal-title":"Annu. Rev. Biomed. Data Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1038\/s41588-023-01475-y","article-title":"Genetic insights into human cortical organization and development through genome-wide analyses of 2,347 neuroimaging phenotypes","volume":"55","author":"Warrier","year":"2023","journal-title":"Nat. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Heng, E., Thanedar, S., and Heng, H.H. (2023). Challenges and Opportunities for Clinical Cytogenetics in the 21st Century. Genes, 14.","DOI":"10.3390\/genes14020493"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.ygeno.2011.05.008","article-title":"Decoding the genome beyond sequencing: The new phase of genomic research","volume":"98","author":"Heng","year":"2011","journal-title":"Genomics"},{"key":"ref_18","unstructured":"Popper, K. (2002). The Logic of Scientific Discovery, Routledge. [2nd ed.]."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Voutsinos, V., Munk, S.H.N., and Oestergaard, V.H. (2018). Common Chromosomal Fragile Sites-Conserved Failure Stories. Genes, 9.","DOI":"10.3390\/genes9120580"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1038\/ncb2773","article-title":"MUS81 Promotes Common Fragile Site Expression","volume":"15","author":"Ying","year":"2013","journal-title":"Nat. Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e2106477118","DOI":"10.1073\/pnas.2106477118","article-title":"Translesion polymerase eta both facilitates DNA replication and promotes increased human genetic variation at common fragile sites","volume":"118","author":"Twayana","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","unstructured":"Fitzgerald, M. (2018). Neurodevelopment and Neurodevelopmental Disorder, IntechOpen."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1146\/annurev-genet-110711-155547","article-title":"Mutations arising during repair of chromosome breaks","volume":"46","author":"Malkova","year":"2012","journal-title":"Annu. Rev. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/s41597-022-01508-x","article-title":"An atlas of endogenous DNA double-strand breaks arising during human neural cell fate determination","volume":"9","author":"Ballarino","year":"2022","journal-title":"Sci. Data"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1016\/j.celrep.2020.01.020","article-title":"A P53-Independent DNA Damage Response Suppresses Oncogenic Proliferation and Genome Instability","volume":"30","author":"Simpson","year":"2020","journal-title":"Cell Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"18613","DOI":"10.1073\/pnas.0703637104","article-title":"Species-specific endogenous retroviruses shape the transcriptional network of the human tumor suppressor protein p53","volume":"104","author":"Wang","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1615\/CritRevImmunol.v35.i5.40","article-title":"The p53 Transcriptional Network Influences Microglia Behavior and Neuroinflammation","volume":"35","author":"Aloi","year":"2015","journal-title":"Crit. Rev. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1002\/humu.24481","article-title":"MicroRNA binding site variation is enriched in psychiatric disorders","volume":"43","author":"Geaghan","year":"2022","journal-title":"Hum. Mutat."},{"key":"ref_29","first-page":"677","article-title":"Schizophrenia-associated single nucleotide polymorphisms affecting microRNA function","volume":"41","author":"Liang","year":"2019","journal-title":"Yi Chuan"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.tins.2010.04.001","article-title":"LINE-1 retrotransposons: Mediators of somatic variation in neuronal genomes?","volume":"33","author":"Singer","year":"2010","journal-title":"Trends Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"eaal1641","DOI":"10.1126\/science.aal1641","article-title":"Brain Somatic Mosaicism Network. Intersection of diverse neuronal genomes and neuropsychiatric disease: The Brain Somatic Mosaicism Network","volume":"356","author":"McConnell","year":"2017","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1176\/ajp.149.8.1116a","article-title":"Schizophrenia and chromosomal fragile sites","volume":"149","author":"Garofalo","year":"1992","journal-title":"Am. J. Psychiatry"},{"key":"ref_33","first-page":"132","article-title":"Evidence of chromosomal fragile sites in schizophrenic patients","volume":"36","author":"Garofalo","year":"1993","journal-title":"Ann. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1002\/ajmg.1320600516","article-title":"Increased chromosomal breakage in Tourette syndrome predicts the possibility of variable multiple gene involvement in spectrum phenotypes: Preliminary findings and hypothesis","volume":"60","author":"Gericke","year":"1995","journal-title":"Am. J. Med. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1002\/(SICI)1096-8628(19960216)67:1<25::AID-AJMG4>3.0.CO;2-R","article-title":"Increased expression of aphidicolin-induced common fragile sites in Tourette syndrome: The key to understand the genetics of comorbid phenotypes?","volume":"67","author":"Gericke","year":"1996","journal-title":"Am. J. Med. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/0306-9877(95)90233-3","article-title":"A paradigmatic shift in the approach to neuropsychiatric gene linkage may require an anthropogenetic perspective","volume":"45","author":"Gericke","year":"1995","journal-title":"Med. Hypotheses"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1007\/BF02267080","article-title":"The enigma of common fragile sites","volume":"97","author":"Simonic","year":"1996","journal-title":"Hum. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1002\/(SICI)1096-8628(19970531)74:3<331::AID-AJMG16>3.0.CO;2-P","article-title":"Additional clinical and cytogenetic findings associated with Rett syndrome","volume":"74","author":"Simonic","year":"1997","journal-title":"Am. J. Med. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1002\/1096-8628(200022)97:2<147::AID-AJMG6>3.0.CO;2-O","article-title":"Rett syndrome: Methyl-CpG-binding protein 2 mutations and phenotype-genotype correlations","volume":"97","author":"Amir","year":"2000","journal-title":"Am. J. Med. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1007\/s004390050894","article-title":"Chromosomal fragile site expression in lymphocytes from patients with schizophrenia","volume":"103","author":"Chen","year":"1998","journal-title":"Hum. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/ajmg.b.20010","article-title":"DNA stability and schizophrenia in twins","volume":"120B","author":"Nguyen","year":"2003","journal-title":"Am. J. Med. Genet. B Neuropsychiatr. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.mehy.2005.06.032","article-title":"Chromosomal fragility, structural rearrangements and mobile element activity may reflect dynamic epigenetic mechanisms of importance in neurobehavioural genetics","volume":"66","author":"Gericke","year":"2006","journal-title":"Med. Hypotheses"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Yurov, Y.B., Iourov, I.Y., Vorsanova, S.G., Liehr, T., Kolotii, A.D., Kutsev, S.I., Pellestor, F., Beresheva, A.K., Demidova, I.A., and Kravets, V.S. (2007). Aneuploidy and confined chromosomal mosaicism in the developing human brain. PLoS ONE., 2.","DOI":"10.1371\/journal.pone.0000558"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.mehy.2008.03.048","article-title":"An integrative view of dynamic genomic elements influencing human brain evolution and individual neurodevelopment","volume":"71","author":"Gericke","year":"2008","journal-title":"Med. Hypotheses"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"86","DOI":"10.17116\/jnevro201611611186-91","article-title":"[Genomic instability in the brain: Chromosomal mosaicism in schizophrenia]","volume":"116","author":"Yurov","year":"2016","journal-title":"Zhurnal Nevrol. I Psikhiatrii Im. SS Korsakova"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"447","DOI":"10.2174\/138920210793176001","article-title":"Genomic and epigenomic instability, fragile sites, schizophrenia and autism","volume":"11","author":"Smith","year":"2010","journal-title":"Curr. Genom."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Iourov, I.Y., Vorsanova, S.G., Yurov, Y.B., and Kutsev, S.I. (2019). Ontogenetic and Pathogenetic Views on Somatic Chromosomal Mosaicism. Genes, 10.","DOI":"10.3390\/genes10050379"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1111\/febs.15849","article-title":"Breaking the paradigm: Early insights from mammalian DNA breakomes","volume":"289","author":"Saayman","year":"2022","journal-title":"FEBS J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1093\/hmg\/ddp470","article-title":"Impaired replication dynamics at the FRA3B common fragile site","volume":"19","author":"Palakodeti","year":"2010","journal-title":"Hum Mol. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Mohanta, T.K., Mishra, A.K., and Al-Harrasi, A. (2021). The 3D Genome: From Structure to Function. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111585"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4519","DOI":"10.1007\/s00018-014-1717-x","article-title":"Are common fragile sites merely structural domains or highly organized \u201cfunctional\u201d units susceptible to oncogenic stress?","volume":"71","author":"Georgakilas","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3613","DOI":"10.1038\/s41467-020-17448-2","article-title":"3D genome organization contributes to genome instability at fragile sites","volume":"11","author":"Sarni","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1159\/000080822","article-title":"Evolutionary breakpoints are co-localized with fragile sites and intrachromosomal telomeric sequences in primates","volume":"108","author":"Giulotto","year":"2005","journal-title":"Cytogenet. Genome Res."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Ram, Y., and Hadany, L. (2014). Stress-induced mutagenesis and complex adaptation. Proc. Biol. Sci., 281.","DOI":"10.1101\/007096"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4393","DOI":"10.1073\/pnas.0700463105","article-title":"Bet-hedging and epigenetic inheritance in bacterial cell development","volume":"105","author":"Veening","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.dnarep.2018.08.019","article-title":"DNA double-strand breaks as drivers of neural genomic change, function, and disease","volume":"71","author":"Alt","year":"2018","journal-title":"DNA Repair"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.cell.2015.12.039","article-title":"Long Neural Genes Harbor Recurrent DNA Break Clusters in Neural Stem\/Progenitor Cells","volume":"164","author":"Wei","year":"2016","journal-title":"Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"985975","DOI":"10.3389\/fgene.2022.985975","article-title":"Fragile sites, chromosomal lesions, tandem repeats, and disease","volume":"13","author":"Mirceta","year":"2022","journal-title":"Front. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1101\/sqb.2004.69.349","article-title":"Restructuring the Genome in Response to Adaptive Challenge: McClintock\u2019s Bold Conjecture Revisited","volume":"69","author":"Jorgensen","year":"2004","journal-title":"Cold Spring Harb. Symp. Quant. Biol."},{"key":"ref_60","unstructured":"McClintock, B. (1978). Stadler Genetics Symposium, University of Missouri."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Barkai, N. (2024, February 15). Department of Molecular Genetics, Weizmann Insitute of Science\u2014Israel. Institut Pasteur Seminar Department of Developmental and Stem Cell Biology1 Feb 2017 \u201cCoupling Phenotypic Persistence to DNA Damage Increases Genetic Diversity in Severe Stress\u201d. Available online: https:\/\/research.pasteur.fr\/en\/event\/seminar-coupling-phenotypic-persistence-to-dna-damage-increases-genetic-diversity-in-severe-stress\/.","DOI":"10.1038\/s41559-016-0016"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1023\/A:1004468625863","article-title":"\u201cThe real point is control\u201d: The reception of Barbara McClintock\u2019s controlling elements","volume":"32","author":"Comfort","year":"1999","journal-title":"J. Hist. Biol."},{"key":"ref_63","first-page":"10286","article-title":"Structural insights into the mechanism of double strand break formation by Hermes, a hAT family eukaryotic DNA transposase","volume":"46","author":"Hickman","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1146\/annurev-genom-082509-141802","article-title":"LINE-1 elements in structural variation and disease","volume":"12","author":"Beck","year":"2011","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"eadh9543","DOI":"10.1126\/sciadv.adh9543","article-title":"LINE-1 retrotransposons drive human neuronal transcriptome complexity and functional diversification","volume":"9","author":"Garza","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.3389\/fimmu.2018.02039","article-title":"Human Endogenous Retroviruses Are Ancient Acquired Elements Still Shaping Innate Immune Responses","volume":"9","author":"Grandi","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/s41398-023-02575-3","article-title":"Patients with psychosis spectrum disorders hospitalized during the COVID-19 pandemic unravel overlooked SARS-CoV-2 past infection clustering with HERV-W ENV expression and chronic inflammation","volume":"13","author":"Tamouza","year":"2023","journal-title":"Transl. Psychiatry"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Nesse, R.M., Bhatnagar, S., and Young, E.A. (2007). Evolutionary Origins and Functions of the Stress Response Encyclopedia of Stress, Elsevier Inc.. [2nd ed.].","DOI":"10.1016\/B978-012373947-6.00150-1"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Caporale, L.H. (2006). The Implicit Genome, Oxford University Press.","DOI":"10.1093\/oso\/9780195172706.001.0001"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/150563a0","article-title":"Canalization of Development and the Inheritance of Acquired characters","volume":"150","author":"Waddington","year":"1942","journal-title":"Nature"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1101\/gr.086546.108","article-title":"Breakpoint regions and homologous synteny blocks in chromosomes have different evolutionary histories","volume":"19","author":"Larkin","year":"2009","journal-title":"Genome Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/nrg2193","article-title":"Gene conversion: Mechanisms, evolution and human disease","volume":"8","author":"Chen","year":"2007","journal-title":"Nat. Rev. Genet."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/0959-437X(95)80046-8","article-title":"The molecular basis of fragile sites in human chromosomes","volume":"5","author":"Sutherland","year":"1995","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"60","DOI":"10.2174\/1389202916666150114223205","article-title":"DNA secondary structure at chromosomal fragile sites in human disease","volume":"16","author":"Thys","year":"2015","journal-title":"Curr. Genom."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/s41380-020-00924-y","article-title":"The neuroendocrine modulation of global DNA methylation in neuropsychiatric disorders","volume":"26","author":"Grevet","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.cobeha.2019.01.008","article-title":"The Conserved Transcriptional Response to Adversity","volume":"28","author":"Cole","year":"2019","journal-title":"Curr. Opin. Behav. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s13148-015-0123-z","article-title":"High cortisol in 5-year-old children causes loss of DNA methylation in SINE retrotransposons: A possible role for ZNF263 in stress-related diseases","volume":"7","author":"Johansson","year":"2015","journal-title":"Clin. Epigenetics"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1042\/EBC20220069","article-title":"Modelling the evolution of novelty: A review","volume":"66","author":"Colizzi","year":"2022","journal-title":"Essays Biochem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"836066","DOI":"10.3389\/fevo.2022.836066","article-title":"The Happy Hopping of Transposons: The Origins of V(D)J Recombination in Adaptive Immunity","volume":"10","author":"Shridharan","year":"2022","journal-title":"Front. Ecol. Evol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"sgab031","DOI":"10.1093\/schizbullopen\/sgab031","article-title":"Inherited L1 Retrotransposon Insertions Associated with Risk for Schizophrenia and Bipolar Disorder","volume":"2","author":"Reiner","year":"2021","journal-title":"Schizophr. Bull. Open"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/s41419-023-05737-9","article-title":"Astrocytes express aberrant immunoglobulins as putative gatekeeper of astrocytes to neuronal progenitor conversion","volume":"14","author":"Capuz","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_82","unstructured":"Dost\u00e1lov\u00e1, V. (2016). Transgenerational Epigenetic Inheritance in Mammals, Faculty of Science Department of Philosophy and History of Science. [Master\u2019s Thesis, Charles University Praha]."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"eabl5621","DOI":"10.1126\/sciadv.abl5621","article-title":"Oncogenic lncRNAs alter epigenetic memory at a fragile chromosomal site in human cancer cells","volume":"8","author":"Arunkumar","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1330345","DOI":"10.3389\/fpsyg.2023.1330345","article-title":"Biological evolution and human cognition are analogous information processing systems","volume":"14","author":"Hidalgo","year":"2024","journal-title":"Front. Psychol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1534\/genetics.117.205039","article-title":"Waddington Redux: De Novo Mutations Underlie the Genetic Assimilation of Stress-Induced Phenocopies in Drosophila melanogaster","volume":"207","author":"Kasinathan","year":"2017","journal-title":"Genetics"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.3389\/fimmu.2017.01611","article-title":"Reverse Transcriptase Mechanism of Somatic Hypermutation: 60 Years of Clonal Selection Theory","volume":"8","author":"Steele","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"S18","DOI":"10.1038\/ng1559","article-title":"Mapping of genetic and epigenetic regulatory networks using microarrays","volume":"37","year":"2005","journal-title":"Nat. Genet."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4315","DOI":"10.1093\/nar\/gkx174","article-title":"Mocap: Large-scale inference of transcription factor binding sites from chromatin accessibility","volume":"45","author":"Chen","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1038\/s41422-020-0376-8","article-title":"Twin peaks: Finding fragile sites with MiDAS-seq","volume":"30","author":"Glover","year":"2020","journal-title":"Cell Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/j.tig.2020.08.004","article-title":"Elucidation of Biological Networks across Complex Diseases Using Single-Cell Omics","volume":"36","author":"Li","year":"2020","journal-title":"Trends Genet."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"653120","DOI":"10.3389\/fnins.2021.653120","article-title":"Altered Gut Microbiota in a Fragile X Syndrome Mouse Model","volume":"15","author":"Altimiras","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1126\/science.1247472","article-title":"Medicine. Combating evolution to fight disease","volume":"343","author":"Rosenberg","year":"2014","journal-title":"Science"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/4\/471\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:25:06Z","timestamp":1760106306000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/4\/471"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,8]]},"references-count":92,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["genes15040471"],"URL":"https:\/\/doi.org\/10.3390\/genes15040471","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,8]]}}}