{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:15:35Z","timestamp":1769040935677,"version":"3.49.0"},"reference-count":39,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T00:00:00Z","timestamp":1594944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002261","name":"Russian Foundation for Basic Research","doi-asserted-by":"publisher","award":["19-015-00122"],"award-info":[{"award-number":["19-015-00122"]}],"id":[{"id":"10.13039\/501100002261","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The frequency of pathogenic large chromosome rearrangements detected in patients with different Mendelian diseases is truly diverse and can be remarkably high. Chromosome breaks could arise through different known mechanisms. Congenital PAX6-associated aniridia is a hereditary eye disorder caused by mutations or chromosome rearrangements involving the PAX6 gene. In our recent study, we identified 11p13 chromosome deletions in 30 out of 91 probands with congenital aniridia or WAGR syndrome (characterized by Wilms\u2019 tumor, Aniridia, and Genitourinary abnormalities as well as mental Retardation). The loss of heterozygosity analysis (LOH) was performed in 10 families with de novo chromosome deletion in proband. In 7 out of 8 informative families, the analysis revealed that deletions occurred at the paternal allele. If paternal origin is not random, chromosome breaks could arise either (i) during spermiogenesis, which is possible due to specific male chromatin epigenetic program and its vulnerability to the breakage-causing factors, or (ii) in early zygotes at a time when chromosomes transmitted from different parents still carry epigenetic marks of the origin, which is also possible due to diverse and asymmetric epigenetic reprogramming occurring in male and female pronuclei. Some new data is needed to make a well-considered conclusion on the reasons for preferential paternal origin of 11p13 deletions.<\/jats:p>","DOI":"10.3390\/genes11070812","type":"journal-article","created":{"date-parts":[[2020,7,21]],"date-time":"2020-07-21T06:38:55Z","timestamp":1595313535000},"page":"812","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Preferentially Paternal Origin of De Novo 11p13 Chromosome Deletions Revealed in Patients with Congenital Aniridia and WAGR Syndrome"],"prefix":"10.3390","volume":"11","author":[{"given":"Tatyana A.","family":"Vasilyeva","sequence":"first","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0972-5118","authenticated-orcid":false,"given":"Andrey V.","family":"Marakhonov","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natella V.","family":"Sukhanova","sequence":"additional","affiliation":[{"name":"Central Clinical Hospital of the Russian Academy of Sciences, 119333 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey I.","family":"Kutsev","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3586-3458","authenticated-orcid":false,"given":"Rena A.","family":"Zinchenko","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,17]]},"reference":[{"key":"ref_1","first-page":"1145","article-title":"Aniridia syndrome: Clinical findings, problematic courses and suggestions for optimization of care (\u201caniridia guide\u201d)","volume":"111","author":"Seitz","year":"2014","journal-title":"Ophthalmologe"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1097\/ICU.0000000000000405","article-title":"PAX6 aniridia syndrome","volume":"28","author":"Lim","year":"2017","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s004390100529","article-title":"Population-based risk estimates of Wilms tumor in sporadic aniridia. A comprehensive mutation screening procedure of PAX6 identifies 80% of mutations in aniridia","volume":"109","author":"Olsen","year":"2001","journal-title":"Hum. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3323","DOI":"10.1093\/hmg\/ddz168","article-title":"LMO2 gene deletions significantly worsen the prognosis of Wilms\u2019 tumor development in patients with WAGR syndrome","volume":"28","author":"Marakhonov","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1002\/ajmg.a.32209","article-title":"Genetic analysis of chromosome 11p13 and thePAX6 gene in a series of 125 cases referred with aniridia","volume":"146","author":"Robinson","year":"2008","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Vasilyeva, T.A., Marakhonov, A.V., Voskresenskaya, A.A., Kadyshev, V.V., K\u00e4smann-Kellner, B., Sukhanova, N.V., Katargina, L.A., Kutsev, S.I., and Zinchenko, R.A. (2020). Analysis of genotype\u2013phenotype correlations in PAX6-associated aniridia. J. Med. Genet.","DOI":"10.1136\/jmedgenet-2019-106172"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"102662","DOI":"10.1016\/j.dnarep.2019.102662","article-title":"The role of RNA and RNA-related proteins in the regulation of DNA double strand break repair pathway choice","volume":"81","author":"Jimeno","year":"2019","journal-title":"DNA Repair"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Karlsson, K.H., and Stenerl\u00f6w, B. (2007). Extensive ssDNA end formation at DNA double-strand breaks in non-homologous end-joining deficient cells during the S phase. BMC Mol. Boil., 8.","DOI":"10.1186\/1471-2199-8-97"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Jabbari, K., Wirtz, J., Rauscher, M., and Wiehe, T. (2019). A common genomic code for chromatin architecture and recombination landscape. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0213278"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.molcel.2019.05.015","article-title":"Spatial Chromosome Folding and Active Transcription Drive DNA Fragility and Formation of Oncogenic MLL Translocations","volume":"75","author":"Gothe","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1101\/gad.288142.116","article-title":"Replication fork instability and the consequences of fork collisions from rereplication","volume":"30","author":"Alexander","year":"2016","journal-title":"Genes Dev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"521","DOI":"10.3389\/fgene.2018.00521","article-title":"Hotspots for Initiation of Meiotic Recombination","volume":"9","author":"Tock","year":"2018","journal-title":"Front. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1111\/cge.13019","article-title":"Molecular analysis of patients with aniridia in Russian Federation broadens the spectrum of PAX6 mutations","volume":"92","author":"Vasilyeva","year":"2017","journal-title":"Clin. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1093\/humupd\/dmr010","article-title":"Complex chromosomal rearrangements: origin and meiotic behavior","volume":"17","author":"Pellestor","year":"2011","journal-title":"Hum. Reprod. Updat."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1136\/jmedgenet-2011-100147","article-title":"De novo copy number variants associated with intellectual disability have a paternal origin and age bias","volume":"48","author":"Pfundt","year":"2011","journal-title":"J. Med. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2766","DOI":"10.1093\/nar\/gkz103","article-title":"Chromatin organization modulates the origin of heritable structural variations in human genome","volume":"47","author":"Roychowdhury","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1086\/522089","article-title":"Type 2 NF1 Deletions Are Highly Unusual by Virtue of the Absence of Nonallelic Homologous Recombination Hotspots and an Apparent Preference for Female Mitotic Recombination","volume":"81","author":"Steinmann","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1159\/000330267","article-title":"Origins and Breakpoint Analyses of Copy Number Variations: Up Close and Personal","volume":"135","year":"2011","journal-title":"Cytogenet. Genome Res."},{"key":"ref_19","first-page":"155","article-title":"Parental origin of de novo constitutional deletions of chromosomal band 11p13","volume":"47","author":"Huff","year":"1990","journal-title":"Am. J. Hum. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1126\/science.1181495","article-title":"Prdm9 Controls Activation of Mammalian Recombination Hotspots","volume":"327","author":"Parvanov","year":"2009","journal-title":"Science"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/nature04112","article-title":"A histone H3 methyltransferase controls epigenetic events required for meiotic prophase","volume":"438","author":"Hayashi","year":"2005","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1086\/302011","article-title":"Comprehensive Human Genetic Maps: Individual and Sex-Specific Variation in Recombination","volume":"63","author":"Broman","year":"1998","journal-title":"Am. J. Hum. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1093\/gbe\/evz058","article-title":"Fine-Scale Characterization of Genomic Structural Variation in the Human Genome Reveals Adaptive and Biomedically Relevant Hotspots","volume":"11","author":"Lin","year":"2019","journal-title":"Genome Boil. Evol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"13815","DOI":"10.1074\/jbc.R117.001561","article-title":"Not just heads and tails: The complexity of the sperm epigenome","volume":"293","author":"Gold","year":"2018","journal-title":"J. Boil. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.bbagrm.2013.08.004","article-title":"Chromatin dynamics during spermiogenesis","volume":"1839","author":"Rathke","year":"2014","journal-title":"Biochim. Biophys. Acta (BBA) Bioenerg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1095\/biolreprod.107.064162","article-title":"DNA Damage Response During Chromatin Remodeling in Elongating Spermatids of Mice1","volume":"78","author":"LeDuc","year":"2008","journal-title":"Boil. Reprod."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1086\/344396","article-title":"Frequent Chromosome Aberrations Revealed by Molecular Cytogenetic Studies in Patients with Aniridia","volume":"71","author":"Crolla","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1134\/S1022795408100062","article-title":"Epimutations of imprinting genes in the human genome: classification, causes, association with hereditary pathology","volume":"44","author":"Lebedev","year":"2008","journal-title":"Russ. J. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"24","DOI":"10.3389\/fcell.2018.00024","article-title":"A Lexicon of DNA Modifications: Their Roles in Embryo Development and the Germline","volume":"6","author":"Zhu","year":"2018","journal-title":"Front. Cell Dev. Boil."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1038\/emboj.2010.80","article-title":"Dynamic link of DNA demethylation, DNA strand breaks and repair in mouse zygotes","volume":"29","author":"Wossidlo","year":"2010","journal-title":"EMBO J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1093\/hmg\/ddn090","article-title":"DNA double-strand break repair in parental chromatin of mouse zygotes, the first cell cycle as an origin of de novo mutation","volume":"17","author":"Derijck","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"14026","DOI":"10.3390\/ijms131114026","article-title":"Types, Causes, Detection and Repair of DNA Fragmentation in Animal and Human Sperm Cells","volume":"13","author":"Gosalvez","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s13072-018-0224-y","article-title":"Oxidative stress in sperm affects the epigenetic reprogramming in early embryonic development","volume":"11","author":"Wyck","year":"2018","journal-title":"Epigenetics Chromatin"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1016\/j.cell.2016.11.009","article-title":"A Surveillance Mechanism Ensures Repair of DNA Lesions during Zygotic Reprogramming","volume":"167","author":"Tachibana","year":"2016","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1080\/19396360701876823","article-title":"Spermiogenesis and DNA Repair: A Possible Etiology of Human Infertility and Genetic Disorders","volume":"54","author":"LeDuc","year":"2008","journal-title":"Syst. Boil. Reprod. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.placenta.2015.01.012","article-title":"Loss of inherited genomic imprints in mice leads to severe disruption in placental lipid metabolism","volume":"36","author":"Himes","year":"2015","journal-title":"Placenta"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1111\/rda.13093","article-title":"DNA methylation and expression of imprinted genes are associated with the viability of different sexual cloned buffaloes","volume":"53","author":"Ruan","year":"2017","journal-title":"Reprod. Domest. Anim."},{"key":"ref_38","first-page":"389","article-title":"Congenital Aniridia","volume":"12","author":"Shaw","year":"1960","journal-title":"Am. J. Hum. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.biocel.2015.04.014","article-title":"Germline-derived DNA methylation and early embryo epigenetic reprogramming: The selected survival of imprints","volume":"67","author":"Monk","year":"2015","journal-title":"Int. J. Biochem. Cell Boil."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/11\/7\/812\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:49:14Z","timestamp":1760176154000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/11\/7\/812"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,17]]},"references-count":39,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2020,7]]}},"alternative-id":["genes11070812"],"URL":"https:\/\/doi.org\/10.3390\/genes11070812","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,17]]}}}