{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:02:44Z","timestamp":1789534964919,"version":"build-2803163510"},"reference-count":136,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003819","name":"Hubei Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["2026AFD065"],"award-info":[{"award-number":["2026AFD065"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012554","name":"Hubei Provincial Department of Education","doi-asserted-by":"publisher","award":["B2024292"],"award-info":[{"award-number":["B2024292"]}],"id":[{"id":"10.13039\/100012554","id-type":"DOI","asserted-by":"publisher"}]},{"award":["B2024292"],"award-info":[{"award-number":["B2024292"]}],"id":[{"id":"https:\/\/ror.org\/05yaa9j15","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Facioscapulohumeral muscular dystrophy (FSHD) is a genetically and epigenetically complex autosomal dominant myopathy that presents formidable challenges to molecular diagnosis and reproductive intervention. The disease is caused by aberrant derepression of the DUX4 retrogene within the D4Z4 macrosatellite repeat array at chromosome 4q35, triggered either by pathological contraction of the array on a permissive 4qA haplotype (FSHD1, ~95% of cases) or by mutations in epigenetic modifier genes SMCHD1, DNMT3B, and LRIF1 that lead to global D4Z4 hypomethylation (FSHD2, ~5% of cases). Traditional approaches (Southern blotting, optical genome mapping, bisulfite sequencing) are discontinuous and labor-intensive. Nanopore ultra-long read sequencing spans the entire D4Z4 array in single reads, simultaneously resolving repeat number, haplotype, and allele-specific CpG methylation without bisulfite conversion. With the telomere-to-telomere (T2T-CHM13) reference genome, long-range haplotype phasing enables preimplantation genetic testing for monogenic conditions (PGT-M) for families with de novo pathogenic variants and somatic mosaicism, groups previously excluded from reproductive genetic intervention. This review systematically examines FSHD molecular mechanisms, the Nanopore diagnostic workflow integrated with T2T-CHM13, Nanopore-based PGT-M clinical data, and future perspectives including R11 pore chemistry, AI-driven bioinformatics, CRISPR-targeted enrichment, and multi-omics integration.<\/jats:p>","DOI":"10.3390\/genes17091104","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T17:14:59Z","timestamp":1789146899000},"page":"1104","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nanopore Ultra-Long Sequencing for FSHD: From Molecular Diagnosis to Preimplantation Genetic Testing"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0142-5495","authenticated-orcid":false,"given":"Jingjing","family":"Li","sequence":"first","affiliation":[{"name":"Center of Applied Biotechnology, School of Life Sciences and Technology, Wuhan University of Bioengineering, Wuhan 430415, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjie","family":"Cheng","sequence":"additional","affiliation":[{"name":"Center of Applied Biotechnology, School of Life Sciences and Technology, Wuhan University of Bioengineering, Wuhan 430415, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Su","sequence":"additional","affiliation":[{"name":"Beijing Bai\u2019an Jimin Medical Technology, Beijing 100080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyuan","family":"Yan","sequence":"additional","affiliation":[{"name":"Center of Applied Biotechnology, School of Life Sciences and Technology, Wuhan University of Bioengineering, Wuhan 430415, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhua","family":"Cao","sequence":"additional","affiliation":[{"name":"Beijing Bai\u2019an Jimin Medical Technology, Beijing 100080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1212\/WNL.0000000000000797","article-title":"Population-based incidence and prevalence of facioscapulohumeral dystrophy","volume":"83","author":"Deenen","year":"2014","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3233\/JND-140045","article-title":"The Epidemiology of Neuromuscular Disorders: A Comprehensive Overview of the Literature","volume":"2","author":"Deenen","year":"2015","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_3","first-page":"100323","article-title":"Prevalence and disease progression of genetically-confirmed facioscapulohumeral muscular dystrophy type 1 (FSHD1) in China between 2001 and 2020","volume":"18","author":"Wang","year":"2022","journal-title":"Lancet Reg. Health West. Pac."},{"key":"ref_4","first-page":"100328","article-title":"Joining mainstream research on Facioscapulohumeral Dystrophy: Disease prevalence in China","volume":"18","author":"Magdinier","year":"2022","journal-title":"Lancet Reg. Health West. Pac."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1212\/WNL.0000000000001783","article-title":"Evidence-based guideline summary: Evaluation, diagnosis, and management of facioscapulohumeral muscular dystrophy","volume":"85","author":"Tawil","year":"2015","journal-title":"Neurology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1212\/CON.0000000000000801","article-title":"Facioscapulohumeral Muscular Dystrophies","volume":"25","author":"Wagner","year":"2019","journal-title":"Continuum"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1136\/practneurol-2015-001353","article-title":"What\u2019s in a name? The clinical features of facioscapulohumeral muscular dystrophy","volume":"16","author":"Mul","year":"2016","journal-title":"Pract. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"21648","DOI":"10.1038\/s41598-020-78578-7","article-title":"Large genotype-phenotype study in carriers of D4Z4 borderline alleles provides guidance for facioscapulohumeral muscular dystrophy diagnosis","volume":"10","author":"Ricci","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e204040","DOI":"10.1001\/jamanetworkopen.2020.4040","article-title":"Phenotypic variability among patients with D4Z4 reduced allele facioscapulohumeral muscular dystrophy","volume":"3","author":"Ruggiero","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0378-1119(99)00267-X","article-title":"Nucleotide sequence of the partially deleted D4Z4 locus in a patient with FSHD identifies a putative gene within each 3.3 kb element","volume":"236","author":"Beckers","year":"1999","journal-title":"Gene"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1126\/science.1189044","article-title":"A unifying genetic model for facioscapulohumeral muscular dystrophy","volume":"329","author":"Lemmers","year":"2010","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Snider, L., Geng, L.N., Lemmers, R.J.L.F., Kyba, M., Ware, C.B., Nelson, A.M., Tawil, R., Filippova, G.N., van der Maarel, S.M., and Tapscott, S.J. (2010). Facioscapulohumeral dystrophy: Incomplete suppression of a retrotransposed gene. PLoS Genet., 6.","DOI":"10.1371\/journal.pgen.1001181"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.devcel.2011.11.013","article-title":"DUX4 activates germline genes, retroelements, and immune mediators: Implications for facioscapulohumeral dystrophy","volume":"22","author":"Geng","year":"2012","journal-title":"Dev. Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/ng1262","article-title":"Hypomethylation of D4Z4 in 4q-linked and non-4q-linked facioscapulohumeral muscular dystrophy","volume":"35","author":"Lemmers","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1212\/01.wnl.0000271391.44352.fe","article-title":"Hypomethylation is restricted to the D4Z4 repeat array in phenotypic FSHD","volume":"69","author":"Wohlgemuth","year":"2007","journal-title":"Neurology"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Zeng, W., de Greef, J.C., Chen, Y.Y., Chien, R., Kong, X., Gregson, H.C., Winokur, S.T., Pyle, A., Robertson, K.D., and Schmiesing, J.A. (2009). Specific loss of histone H3 lysine 9 trimethylation and HP1\u03b3\/cohesin binding at D4Z4 repeats is associated with facioscapulohumeral dystrophy (FSHD). PLoS Genet., 5.","DOI":"10.1371\/journal.pgen.1000559"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.cell.2012.03.035","article-title":"A long ncRNA links copy number variation to a polycomb\/trithorax epigenetic switch in FSHD muscular dystrophy","volume":"149","author":"Cabianca","year":"2012","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1038\/ng.2454","article-title":"Digenic inheritance of an SMCHD1 mutation and an FSHD-permissive D4Z4 allele causes facioscapulohumeral muscular dystrophy type 2","volume":"44","author":"Lemmers","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1016\/j.ajhg.2016.03.013","article-title":"Mutations in DNMT3B modify epigenetic repression of the D4Z4 repeat and the penetrance of facioscapulohumeral dystrophy","volume":"98","author":"Lemmers","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1093\/hmg\/ddu486","article-title":"Inter-individual differences in CpG methylation at D4Z4 correlate with clinical variability in FSHD1 and FSHD2","volume":"24","author":"Lemmers","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5342","DOI":"10.1093\/hmg\/ddu251","article-title":"DUX4-induced gene expression is the major molecular signature in FSHD skeletal muscle","volume":"23","author":"Yao","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1038\/ng.3846","article-title":"Conservation and innovation in the DUX4-family gene network","volume":"49","author":"Whiddon","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1038\/ng.3844","article-title":"Conserved roles of mouse DUX and human DUX4 in activating cleavage-stage genes and MERVL\/HERVL retrotransposons","volume":"49","author":"Hendrickson","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"18157","DOI":"10.1073\/pnas.0708659104","article-title":"DUX4, a candidate gene of facioscapulohumeral muscular dystrophy, encodes a transcriptional activator of PITX1","volume":"104","author":"Dixit","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5901","DOI":"10.1093\/hmg\/ddv315","article-title":"Endogenous DUX4 expression in FSHD myotubes is sufficient to cause cell death and disrupts RNA splicing and cell migration pathways","volume":"24","author":"Rickard","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Shadle, S.C., Zhong, J.W., Campbell, A.E., Conerly, M.L., Jagannathan, S., Wong, C.-J., Morello, T.D., van der Maarel, S.M., and Tapscott, S.J. (2017). DUX4-induced dsRNA and MYC mRNA stabilization activate apoptotic pathways in human cell models of facioscapulohumeral dystrophy. PLoS Genet., 13.","DOI":"10.1371\/journal.pgen.1006658"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1002\/ana.22275","article-title":"DUX4, a candidate gene for facioscapulohumeral muscular dystrophy, causes p53-dependent myopathy in vivo","volume":"69","author":"Wallace","year":"2011","journal-title":"Ann. Neurol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2766","DOI":"10.1038\/emboj.2008.201","article-title":"An isogenetic myoblast expression screen identifies DUX4-mediated FSHD-associated molecular pathologies","volume":"27","author":"Bosnakovski","year":"2008","journal-title":"EMBO J."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Vanderplanck, C., Ansseau, E., Charron, S., Stricwant, N., Tassin, A., Laoudj-Chenivesse, D., Wilton, S.D., Copp\u00e9e, F., and Belayew, A. (2011). The FSHD atrophic myotube phenotype is caused by DUX4 expression. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0026820"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1038\/s41467-017-01200-4","article-title":"PAX7 target genes are globally repressed in facioscapulohumeral muscular dystrophy skeletal muscle","volume":"8","author":"Banerji","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.nmd.2020.03.001","article-title":"Facioscapulohumeral muscular dystrophy 1 patients participating in the UK FSHD registry can be subdivided into 4 patterns of self-reported symptoms","volume":"30","author":"Banerji","year":"2020","journal-title":"Neuromuscul. Disord."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1101\/gr.277871.123","article-title":"Deciphering D4Z4 CpG methylation gradients in fascioscapulohumeral muscular dystrophy using nanopore sequencing","volume":"33","author":"Butterfield","year":"2023","journal-title":"Genome Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1126\/science.abj6987","article-title":"The complete sequence of a human genome","volume":"376","author":"Nurk","year":"2022","journal-title":"Science"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/cge.14533","article-title":"Best practice guidelines on genetic diagnostics of facioscapulohumeral muscular dystrophy: Update of the 2012 guidelines","volume":"106","author":"Giardina","year":"2024","journal-title":"Clin. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1016\/j.jmoldx.2021.07.021","article-title":"Validation of Optical Genome Mapping for the Molecular Diagnosis of Facioscapulohumeral Muscular Dystrophy","volume":"23","author":"Stence","year":"2021","journal-title":"J. Mol. Diagn."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e200107","DOI":"10.1212\/NXG.0000000000200107","article-title":"Molecular diagnosis of facioscapulohumeral muscular dystrophy in patients clinically suspected of FSHD using optical genome mapping","volume":"9","author":"Guruju","year":"2023","journal-title":"Neurol. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e200389","DOI":"10.1212\/NXG.0000000000200389","article-title":"Proband Nanopore Long-Read Genome Sequencing Facilitates Preimplantation Genetic Testing for Facioscapulohumeral Muscular Dystrophy","volume":"12","author":"Xu","year":"2026","journal-title":"Neurol. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"104879","DOI":"10.1016\/j.rbmo.2025.104879","article-title":"Preimplantation genetic testing for facioscapulohumeral dystrophy caused by contractions of 4q35 D4Z4 repeats","volume":"51","author":"Hu","year":"2025","journal-title":"Reprod. Biomed. Online"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"ESHRE PGT-M Working Group, Carvalho, F., Moutou, C., Dimitriadou, E., Dreesen, J., Gim\u00e9nez, C., Goossens, V., Kakourou, G., Vermeulen, N., and Zuccarello, D. (2020). ESHRE PGT Consortium good practice recommendations for the detection of monogenic disorders. Hum. Reprod. Open, 2020, hoaa018.","DOI":"10.1093\/hropen\/hoaa018"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e19","DOI":"10.1016\/j.fertnstert.2022.08.074","article-title":"Review of recombination events observed in preimplantation genetic testing for monogenic disorders (PGT-M) over a 2 year period","volume":"118","author":"Pai","year":"2022","journal-title":"Fertil. Steril."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/nbt.3423","article-title":"Three decades of nanopore sequencing","volume":"34","author":"Deamer","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1186\/s13059-016-1103-0","article-title":"The Oxford Nanopore MinION: Delivery of nanopore sequencing to the genomics community","volume":"17","author":"Jain","year":"2016","journal-title":"Genome Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/nbt.4060","article-title":"Nanopore sequencing and assembly of a human genome with ultra-long reads","volume":"36","author":"Jain","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1038\/s41587-021-01108-x","article-title":"Nanopore sequencing technology, bioinformatics and applications","volume":"39","author":"Wang","year":"2021","journal-title":"Nat. Biotechnol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1186\/s12967-024-05259-8","article-title":"Comprehensive genetic analysis of facioscapulohumeral muscular dystrophy by Nanopore long-read whole-genome sequencing","volume":"22","author":"Huang","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/nmeth.4184","article-title":"Detecting DNA cytosine methylation using nanopore sequencing","volume":"14","author":"Simpson","year":"2017","journal-title":"Nat. Methods"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/nmeth.4189","article-title":"Mapping DNA methylation with high-throughput nanopore sequencing","volume":"14","author":"Rand","year":"2017","journal-title":"Nat. Methods"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4586","DOI":"10.1093\/bioinformatics\/btz276","article-title":"DeepSignal: Detecting DNA methylation state from Nanopore sequencing reads using deep-learning","volume":"35","author":"Ni","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/s41587-020-0719-5","article-title":"Fully phased human genome assembly without parental data using single-cell strand sequencing and long reads","volume":"39","author":"Porubsky","year":"2021","journal-title":"Nat. Biotechnol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1038\/s41467-020-20536-y","article-title":"Extended haplotype-phasing of long-read de novo genome assemblies using Hi-C","volume":"12","author":"Kronenberg","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"eabl3533","DOI":"10.1126\/science.abl3533","article-title":"A complete reference genome improves analysis of human genetic variation","volume":"376","author":"Aganezov","year":"2022","journal-title":"Science"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"eabj6965","DOI":"10.1126\/science.abj6965","article-title":"Segmental duplications and their variation in a complete human genome","volume":"376","author":"Vollger","year":"2022","journal-title":"Science"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"eabl4178","DOI":"10.1126\/science.abl4178","article-title":"Complete genomic and epigenetic maps of human centromeres","volume":"376","author":"Altemose","year":"2022","journal-title":"Science"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"eabk3112","DOI":"10.1126\/science.abk3112","article-title":"From telomere to telomere: The transcriptional and epigenetic state of human repeat elements","volume":"376","author":"Hoyt","year":"2022","journal-title":"Science"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1093\/hmg\/3.8.1287","article-title":"Analysis of the tandem repeat locus D4Z4 associated with facioscapulohumeral muscular dystrophy","volume":"3","author":"Hewitt","year":"1994","journal-title":"Hum. Mol. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1006\/geno.1995.1166","article-title":"The FSHD-associated repeat, D4Z4, is a member of a dispersed family of homeobox-containing repeats, subsets of which are clustered on the short arms of the acrocentric chromosomes","volume":"28","author":"Lyle","year":"1995","journal-title":"Genomics"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/ng0992-26","article-title":"Chromosome 4q DNA rearrangements associated with facioscapulohumeral muscular dystrophy","volume":"2","author":"Wijmenga","year":"1992","journal-title":"Nat. Genet."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2895","DOI":"10.1093\/hmg\/ddg327","article-title":"Expression profiling of FSHD muscle supports a defect in specific stages of myogenic differentiation","volume":"12","author":"Winokur","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.molmed.2011.01.001","article-title":"Facioscapulohumeral muscular dystrophy and DUX4: Breaking the silence","volume":"17","author":"Tawil","year":"2011","journal-title":"Trends Mol. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/s41431-025-02000-x","article-title":"Rethinking genomics of facioscapulohumeral muscular dystrophy in the telomere-to-telomere era: Pitfalls in the hidden landscape of D4Z4 repeats","volume":"34","author":"Salsi","year":"2026","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1016\/j.celrep.2019.10.025","article-title":"DUX4-induced histone variants H3.X and H3.Y mark DUX4 target genes for expression","volume":"29","author":"Resnick","year":"2019","journal-title":"Cell Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/2044-5040-4-12","article-title":"Facioscapulohumeral dystrophy: The path to consensus on pathophysiology","volume":"4","author":"Tawil","year":"2014","journal-title":"Skelet. Muscle"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e2441","DOI":"10.1212\/WNL.0000000000009617","article-title":"Homozygous nonsense variant in LRIF1 associated with facioscapulohumeral muscular dystrophy","volume":"94","author":"Hamanaka","year":"2020","journal-title":"Neurology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2822","DOI":"10.1093\/nar\/gkz005","article-title":"SMCHD1 is involved in de novo methylation of the DUX4-encoding D4Z4 macrosatellite","volume":"47","author":"Dion","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1080\/15592294.2015.1113798","article-title":"Increased DUX4 expression during muscle differentiation correlates with decreased SMCHD1 protein levels at D4Z4","volume":"10","author":"Balog","year":"2015","journal-title":"Epigenetics"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"eadn7732","DOI":"10.1126\/sciadv.adn7732","article-title":"DNMT3B splicing dysregulation mediated by SMCHD1 loss contributes to DUX4 overexpression and FSHD pathogenesis","volume":"10","author":"Engal","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s13395-020-00247-0","article-title":"Dnmt3b regulates DUX4 expression in a tissue-dependent manner in transgenic D4Z4 mice","volume":"10","author":"Bouwman","year":"2020","journal-title":"Skelet. Muscle"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e2273","DOI":"10.1212\/WNL.0000000000007456","article-title":"FSHD1 and FSHD2 form a disease continuum","volume":"92","author":"Sacconi","year":"2019","journal-title":"Neurology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1868-7083-6-23","article-title":"Identifying diagnostic DNA methylation profiles for facioscapulohumeral muscular dystrophy in blood and saliva using bisulfite sequencing","volume":"6","author":"Jones","year":"2014","journal-title":"Clin. Epigenetics"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1002\/humu.21091","article-title":"Common epigenetic changes of D4Z4 in contraction-dependent and contraction-independent FSHD","volume":"30","author":"Lemmers","year":"2009","journal-title":"Hum. Mutat."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s40246-026-00921-2","article-title":"DUCKS4: A comprehensive workflow for Nanopore sequencing analysis of facioscapulohumeral muscular dystrophy (FSHD)","volume":"20","author":"Madritsch","year":"2026","journal-title":"Hum. Genom."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/j.nmd.2015.08.008","article-title":"Molecular combing compared to Southern blot for measuring D4Z4 contractions in FSHD","volume":"25","author":"Vasale","year":"2015","journal-title":"Neuromuscul. Disord."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1002\/ana.22513","article-title":"Molecular combing reveals allelic combinations in facioscapulohumeral dystrophy","volume":"70","author":"Nguyen","year":"2011","journal-title":"Ann. Neurol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1002\/humu.23304","article-title":"Molecular combing reveals complex 4q35 rearrangements in Facioscapulohumeral dystrophy","volume":"38","author":"Nguyen","year":"2017","journal-title":"Hum. Mutat."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e275","DOI":"10.1016\/j.fertnstert.2023.08.809","article-title":"Affect of chromosome recombination in target genes on PGT-M diagnosis using karyomapping analysis","volume":"120","author":"Park","year":"2023","journal-title":"Fertil. Steril."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1038\/nprot.2006.326","article-title":"Whole-genome multiple displacement amplification from single cells","volume":"1","author":"Spits","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"101025","DOI":"10.1016\/j.crmeth.2025.101025","article-title":"Differential performance of strategies for single-cell whole-genome amplification","volume":"5","author":"Prieto","year":"2025","journal-title":"Cell Rep. Methods"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"13770","DOI":"10.1073\/pnas.93.24.13770","article-title":"Characterization of individual polynucleotide molecules using a membrane channel","volume":"93","author":"Kasianowicz","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1073\/pnas.97.3.1079","article-title":"Rapid nanopore discrimination between single polynucleotide molecules","volume":"97","author":"Meller","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/nbt.2950","article-title":"Decoding long nanopore sequencing reads of natural DNA","volume":"32","author":"Laszlo","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1186\/s13059-019-1727-y","article-title":"Performance of neural network basecalling tools for Oxford Nanopore sequencing","volume":"20","author":"Wick","year":"2019","journal-title":"Genome Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"20647","DOI":"10.1073\/pnas.0807514106","article-title":"Single-molecule DNA detection with an engineered MspA protein nanopore","volume":"105","author":"Butler","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/nbt.2171","article-title":"Reading DNA at single-nucleotide resolution with a mutant MspA nanopore and phi29 DNA polymerase","volume":"30","author":"Manrao","year":"2012","journal-title":"Nat. Biotechnol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/nbt.2147","article-title":"Automated forward and reverse ratcheting of DNA in a nanopore at 5-\u00c5 precision","volume":"30","author":"Cherf","year":"2012","journal-title":"Nat. Biotechnol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1038\/s41592-022-01539-7","article-title":"Oxford Nanopore R10.4 long-read sequencing enables the generation of near-finished bacterial genomes from pure cultures and metagenomes without short-read or reference polishing","volume":"19","author":"Sereika","year":"2022","journal-title":"Nat. Methods"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1038\/s41592-023-01993-x","article-title":"Scalable Nanopore sequencing of human genomes provides a comprehensive view of haplotype-resolved variation and methylation","volume":"20","author":"Kolmogorov","year":"2023","journal-title":"Nat. Methods"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1101\/gr.240739.118","article-title":"Long-read single-molecule maps of the functional methylome","volume":"29","author":"Sharim","year":"2019","journal-title":"Genome Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1186\/s13059-021-02510-z","article-title":"DNA methylation-calling tools for Oxford Nanopore sequencing: A survey and human epigenome-wide evaluation","volume":"22","author":"Liu","year":"2021","journal-title":"Genome Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1136\/jmedgenet-2019-106402","article-title":"Intronic SMCHD1 variants in FSHD: Testing the potential for CRISPR-Cas9 genome editing","volume":"56","author":"Goossens","year":"2019","journal-title":"J. Med. Genet."},{"key":"ref_90","first-page":"827","article-title":"Complete genetic and epigenetic architecture of D4Z4 macrosatellites in FSHD, BAMS, and reference cohorts with D4Z4End2End","volume":"36","author":"Xiao","year":"2026","journal-title":"Genome Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nrg1322","article-title":"An assessment of the sequence gaps: Unfinished business in a finished human genome","volume":"5","author":"Eichler","year":"2004","journal-title":"Nat. Rev. Genet."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1016\/j.ajhg.2021.06.006","article-title":"Targeted long-read sequencing identifies missing disease-causing variation","volume":"108","author":"Miller","year":"2021","journal-title":"Am. J. Hum. Genet."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/s41586-023-05896-x","article-title":"A draft human pangenome reference","volume":"617","author":"Liao","year":"2023","journal-title":"Nature"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1146\/annurev-genom-120120-081921","article-title":"The Need for a Human Pangenome Reference Sequence","volume":"22","author":"Miga","year":"2021","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Practice Committee and Genetic Counseling Professional Group of the American Society for Reproductive Medicine, and American Society for Reproductive Medicine (2023). Indications and management of preimplantation genetic testing for monogenic conditions: A committee opinion. Fertil. Steril., 120, 61\u201371.","DOI":"10.1016\/j.fertnstert.2023.03.003"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1007\/s00404-024-07370-z","article-title":"Preimplantation genetic testing in the current era, a review","volume":"309","author":"Tian","year":"2024","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1038\/344768a0","article-title":"Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification","volume":"344","author":"Handyside","year":"1990","journal-title":"Nature"},{"key":"ref_98","first-page":"236","article-title":"Comprehensive preimplantation genetic testing by massively parallel sequencing","volume":"36","author":"Chen","year":"2021","journal-title":"Hum. Reprod."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"100604","DOI":"10.1016\/j.gimo.2023.100604","article-title":"P557: Preimplantation genetic diagnosis for facioscapulohumeral muscular dystrophy","volume":"1","author":"Shani","year":"2023","journal-title":"Genet. Med. Open"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1007\/s10815-024-03076-y","article-title":"Mapping ethical, legal, and social implications (ELSI) of preimplantation genetic testing (PGT)","volume":"41","author":"Alon","year":"2024","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1002\/jgc4.1471","article-title":"Ethical and moral perspectives of individuals who considered\/used preimplantation (embryo) genetic testing","volume":"31","author":"Zhang","year":"2022","journal-title":"J. Genet. Couns."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.ejogrb.2020.08.001","article-title":"Non-invasive prenatal diagnosis and screening for monogenic disorders","volume":"253","author":"Scotchman","year":"2020","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"e25029","DOI":"10.1002\/jcla.25029","article-title":"Evaluation of Automated Magnetic Bead-Based DNA Extraction for Detection of Short Tandem Repeat Expansions with Nanopore Sequencing","volume":"38","author":"Faust","year":"2024","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1093\/bib\/bby017","article-title":"Nanopore sequencing technology and tools for genome assembly: Computational analysis of the current state, bottlenecks and future directions","volume":"20","author":"Kim","year":"2019","journal-title":"Brief. Bioinform."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"3094","DOI":"10.1093\/bioinformatics\/bty191","article-title":"Minimap2: Pairwise alignment for nucleotide sequences","volume":"34","author":"Li","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1038\/s41592-021-01299-w","article-title":"Haplotype-aware variant calling with PEPPER-Margin-DeepVariant enables high accuracy in nanopore long-reads","volume":"18","author":"Shafin","year":"2021","journal-title":"Nat. Methods"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/s41576-021-00367-3","article-title":"Towards population-scale long-read sequencing","volume":"22","author":"Weissensteiner","year":"2021","journal-title":"Nat. Rev. Genet."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1038\/s41592-023-01932-w","article-title":"A survey of algorithms for the detection of genomic structural variants from long-read sequencing data","volume":"20","author":"Ahsan","year":"2023","journal-title":"Nat. Methods"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/s41587-020-0731-9","article-title":"Targeted nanopore sequencing by real-time mapping of raw electrical signal with UNCALLED","volume":"39","author":"Kovaka","year":"2021","journal-title":"Nat. Biotechnol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/s41587-020-00746-x","article-title":"Readfish enables targeted nanopore sequencing of gigabase-sized genomes","volume":"39","author":"Payne","year":"2021","journal-title":"Nat. Biotechnol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/s41587-020-0407-5","article-title":"Targeted nanopore sequencing with Cas9-guided adapter ligation","volume":"38","author":"Gilpatrick","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2861","DOI":"10.1038\/s41467-020-16641-7","article-title":"Partner independent fusion gene detection by multiplexed CRISPR-Cas9 enrichment and long read nanopore sequencing","volume":"11","author":"Stangl","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/nmeth.4577","article-title":"Highly parallel direct RNA sequencing on an array of nanopores","volume":"15","author":"Garalde","year":"2018","journal-title":"Nat. Methods"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1038\/s41592-019-0617-2","article-title":"Nanopore native RNA sequencing of a human poly(A) transcriptome","volume":"16","author":"Workman","year":"2019","journal-title":"Nat. Methods"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"7198","DOI":"10.1038\/s41467-021-27393-3","article-title":"RNA modifications detection by comparative Nanopore direct RNA sequencing","volume":"12","author":"Leger","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1093\/hmg\/ddab063","article-title":"Nanopore direct RNA sequencing detects DUX4-activated repeats and isoforms in human muscle cells","volume":"30","author":"Mitsuhashi","year":"2021","journal-title":"Hum. Mol. Genet."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1038\/s41592-022-01633-w","article-title":"Advances in nanopore direct RNA sequencing","volume":"19","author":"Jain","year":"2022","journal-title":"Nat. Methods"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/S1474-4422(24)00073-5","article-title":"Safety and efficacy of losmapimod in facioscapulohumeral muscular dystrophy (ReDUX4): A randomised, double-blind, placebo-controlled phase 2b trial","volume":"23","author":"Tawil","year":"2024","journal-title":"Lancet Neurol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"4658","DOI":"10.1111\/bcp.14884","article-title":"Phase 1 clinical trial of losmapimod in facioscapulohumeral dystrophy: Safety, tolerability, pharmacokinetics, and target engagement","volume":"87","author":"Mellion","year":"2021","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1124\/jpet.119.259663","article-title":"Clinically advanced p38 inhibitors suppress DUX4 expression in cellular and animal models of facioscapulohumeral muscular dystrophy","volume":"370","author":"Oliva","year":"2019","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Ansseau, E., Vanderplanck, C., Wauters, A., Harper, S.Q., Copp\u00e9e, F., and Belayew, A. (2017). Antisense oligonucleotides used to target the DUX4 mRNA as therapeutic approaches in facioscapulohumeral muscular dystrophy (FSHD). Genes, 8.","DOI":"10.3390\/genes8030093"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1093\/hmg\/ddw015","article-title":"Antisense targeting of 3\u2032 end elements involved in DUX4 mRNA processing is an efficient therapeutic strategy for facioscapulohumeral dystrophy: A new gene-silencing approach","volume":"25","author":"Marsollier","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1038\/mt.2012.68","article-title":"RNA interference inhibits DUX4-induced muscle toxicity in vivo: Implications for a targeted FSHD therapy","volume":"20","author":"Wallace","year":"2012","journal-title":"Mol. Ther."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s13395-017-0134-x","article-title":"BET bromodomain inhibitors and agonists of the beta-2 adrenergic receptor identified in screens for compounds that inhibit DUX4 expression in FSHD muscle cells","volume":"7","author":"Campbell","year":"2017","journal-title":"Skelet. Muscle"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.nmd.2007.04.002","article-title":"The DUX4 gene at the FSHD1A locus encodes a pro-apoptotic protein","volume":"17","author":"Kowaljow","year":"2007","journal-title":"Neuromuscul. Disord."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1007\/s11910-016-0667-0","article-title":"Facioscapulohumeral Dystrophy","volume":"16","author":"Wang","year":"2016","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"5161","DOI":"10.1093\/nar\/gkw141","article-title":"DUX4 recruits p300\/CBP through its C-terminus and induces global H3K27 acetylation changes","volume":"44","author":"Choi","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_128","first-page":"4419","article-title":"Model systems of DUX4 expression recapitulate the transcriptional profile of FSHD cells","volume":"25","author":"Jagannathan","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"4661","DOI":"10.1093\/hmg\/ddt314","article-title":"Wnt\/\u03b2-catenin signaling suppresses DUX4 expression and prevents apoptosis of FSHD muscle cells","volume":"22","author":"Block","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Bodega, B., Ramirez, G.D., Grasser, F., Cheli, S., Brunelli, S., Mora, M., Meneveri, R., Marozzi, A., Mueller, S., and Battaglioli, E. (2009). Remodeling of the chromatin structure of the facioscapulohumeral muscular dystrophy (FSHD) locus and upregulation of FSHD-related gene 1 (FRG1) expression during human myogenic differentiation. BMC Biol., 7.","DOI":"10.1186\/1741-7007-7-41"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1136\/jmedgenet-2015-103436","article-title":"Allele-specific DNA hypomethylation characterises FSHD1 and FSHD2","volume":"53","author":"Calandra","year":"2016","journal-title":"J. Med. Genet."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/mt.2015.200","article-title":"CRISPR\/dCas9-mediated transcriptional inhibition ameliorates the epigenetic dysregulation at D4Z4 and represses DUX4-fl in FSH muscular dystrophy","volume":"24","author":"Himeda","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"10327","DOI":"10.1038\/s41598-019-46861-x","article-title":"Analysis of the 4q35 chromatin organization reveals distinct long-range interactions in patients affected with Facio-Scapulo-Humeral Dystrophy","volume":"9","author":"Gaillard","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1136\/jmedgenet-2011-100101","article-title":"Patients with a phenotype consistent with facioscapulohumeral muscular dystrophy display genetic and epigenetic heterogeneity","volume":"49","author":"Sacconi","year":"2012","journal-title":"J. Med. Genet."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s41431-017-0015-0","article-title":"Deep characterization of a common D4Z4 variant identifies biallelic DUX4 expression as a modifier for disease penetrance in FSHD2","volume":"26","author":"Lemmers","year":"2018","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1111\/cge.13726","article-title":"Consequences of epigenetic derepression in facioscapulohumeral muscular dystrophy","volume":"97","author":"Greco","year":"2020","journal-title":"Clin. Genet."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/9\/1104\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T04:15:12Z","timestamp":1789532112000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/9\/1104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,11]]},"references-count":136,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["genes17091104"],"URL":"https:\/\/doi.org\/10.3390\/genes17091104","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,11]]}}}