{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T17:36:02Z","timestamp":1790444162234,"version":"4.1.0"},"reference-count":31,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T00:00:00Z","timestamp":1641859200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["FOR 2488, EXC 22167-390884018"],"award-info":[{"award-number":["FOR 2488, EXC 22167-390884018"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017694","name":"Hermann and Lilly Schilling Foundation","doi-asserted-by":"publisher","award":["N.A."],"award-info":[{"award-number":["N.A."]}],"id":[{"id":"10.13039\/100017694","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Community","award":["SysMedPD"],"award-info":[{"award-number":["SysMedPD"]}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["N.A."],"award-info":[{"award-number":["N.A."]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014381","name":"Peter and Traudl Engelhorn Foundation","doi-asserted-by":"publisher","award":["N.A."],"award-info":[{"award-number":["N.A."]}],"id":[{"id":"10.13039\/501100014381","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Center for XDP","award":["CCXDP"],"award-info":[{"award-number":["CCXDP"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: X-linked dystonia-parkinsonism (XDP) is an adult-onset neurodegenerative disorder characterized by progressive dystonia and parkinsonism. It is caused by a SINE-VNTR-Alu (SVA) retrotransposon insertion in the TAF1 gene with a polymorphic (CCCTCT)n domain that acts as a genetic modifier of disease onset and expressivity. Methods: Herein, we used Nanopore sequencing to investigate SVA genetic variability and methylation. We used blood-derived DNA from 96 XDP patients for amplicon-based deep Nanopore sequencing and validated it with fragment analysis which was performed using fluorescence-based PCR. To detect methylation from blood- and brain-derived DNA, we used a Cas9-targeted approach. Results: High concordance was observed for hexanucleotide repeat numbers detected with Nanopore sequencing and fragment analysis. Within the SVA locus, there was no difference in genetic variability other than variations of the repeat motif between patients. We detected high CpG methylation frequency (MF) of the SVA and flanking regions (mean MF = 0.94, SD = \u00b10.12). Our preliminary results suggest only subtle differences between the XDP patient and the control in predicted enhancer sites directly flanking the SVA locus. Conclusions: Nanopore sequencing can reliably detect SVA hexanucleotide repeat numbers, methylation and, lastly, variation in the repeat motif.<\/jats:p>","DOI":"10.3390\/genes13010126","type":"journal-article","created":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T14:05:07Z","timestamp":1641909907000},"page":"126","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Elucidating Hexanucleotide Repeat Number and Methylation within the X-Linked Dystonia-Parkinsonism (XDP)-Related SVA Retrotransposon in TAF1 with Nanopore Sequencing"],"prefix":"10.3390","volume":"13","author":[{"given":"Theresa","family":"L\u00fcth","sequence":"first","affiliation":[{"name":"Institute of Neurogenetics, University of Luebeck, 23538 Luebeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"La\u03b2","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics, University of Luebeck, 23538 Luebeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susen","family":"Schaake","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics, University of Luebeck, 23538 Luebeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4004-0464","authenticated-orcid":false,"given":"Inken","family":"Wohlers","sequence":"additional","affiliation":[{"name":"Medical Systems Biology Division, Luebeck Institute of Experimental Dermatology, University of Luebeck, 23538 Luebeck, Germany"},{"name":"Institute for Cardiogenetics, University of Luebeck, 23538 Luebeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Pozojevic","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics, University of Luebeck, 23538 Luebeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5317-7369","authenticated-orcid":false,"given":"Roland Dominic G.","family":"Jamora","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, College of Medicine, Philippine General Hospital, University of the Philippines Manila, Manila 1000, Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6387-1389","authenticated-orcid":false,"given":"Raymond L.","family":"Rosales","sequence":"additional","affiliation":[{"name":"Department of Neurology and Psychiatry, The Hospital Neuroscience Institute, University of Santo Tomas, Manila 1008, Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Br\u00fcggemann","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics, University of Luebeck, 23538 Luebeck, Germany"},{"name":"Department of Neurology, University of Luebeck, 23538 Luebeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Saranza","sequence":"additional","affiliation":[{"name":"Section of Neurology, Department of Internal Medicine, Chong Hua Hospital, Cebu City 6000, Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cid Czarina E.","family":"Diesta","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Movement Disorders Clinic, Makati Medical Center, Makati 1229, Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Schl\u00fcter","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics, University of Luebeck, 23538 Luebeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronnie","family":"Tse","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics, University of Luebeck, 23538 Luebeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles Jourdan","family":"Reyes","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics, University of Luebeck, 23538 Luebeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Brand","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics, University of Luebeck, 23538 Luebeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4763-4521","authenticated-orcid":false,"given":"Hauke","family":"Busch","sequence":"additional","affiliation":[{"name":"Medical Systems Biology Division, Luebeck Institute of Experimental Dermatology, University of Luebeck, 23538 Luebeck, Germany"},{"name":"Institute for Cardiogenetics, University of Luebeck, 23538 Luebeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Klein","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics, University of Luebeck, 23538 Luebeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Westenberger","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics, University of Luebeck, 23538 Luebeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Trinh","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics, University of Luebeck, 23538 Luebeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,11]]},"reference":[{"key":"ref_1","first-page":"137","article-title":"Torsion dystonia in Panay, Philippines","volume":"14","author":"Lee","year":"1976","journal-title":"Adv. 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