Academic Journal
Resolving the dark matter of ABCA4 for 1054 Stargardt disease probands through integrated genomics and transcriptomics
العنوان: | Resolving the dark matter of ABCA4 for 1054 Stargardt disease probands through integrated genomics and transcriptomics |
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المؤلفون: | Khan, Mubeen, Cornelis, Stéphanie S., Del Pozo Valero, Marta, Whelan, Laura, Runhart, Esmee H., Mishra, Ketan, Bults, Femke, AlSwaiti, Yahya, AlTalbishi, Alaa, De Baere, Elfride, Banfi, Sandro, Banin, Eyal, Bauwens, Miriam, Ben Yosef, Tamar, Boon, Camiel J. F., van den Born, L. Ingeborgh, Defoort, Sabine, Devos, Aurore, Dockery, Adrian, Dudakova, Lubica, Fakin, Ana, Farrar, G. Jane, Ferraz Sallum, Juliana Maria, Fujinami, Kaoru, Gilissen, Christian, Glavac, Damjan, Gorin, Michael B., Greenberg, Jacquie, Hayashi, Takaaki, Hettinga, Ymkje M., Hoischen, Alexander, Hoyng, Carel B., Hufendiek, Karsten, Jägle, Herbert, Kamakari, Smaragda, Karali, Marianthi, Kellner, Ulrich, Klaver, Caroline C. W., Kousal, Bohdan, Lamey, Tina M., MacDonald, Ian M., Matynia, Anna, McLaren, Terri L., Mena, Marcela D., Meunier, Isabelle, Miller, Rianne, Newman, Hadas, Ntozini, Buhle, Oldak, Monika, Pieterse, Marc, Podhajcer, Osvaldo Luis, Puech, Bernard, Ramesar, Raj, Rüther, Klaus, Salameh, Manar, Salles, Mariana Vallim, Sharon, Dror, Simonelli, Francesca, Spital, Georg, Steehouwer, Marloes, Szaflik, Jacek P., Thompson, Jennifer A., Thuillier, Caroline, Tracewska, Anna M., van Zweeden, Martine, Vincent, Andrea L., Zanlonghi, Xavier, Liskova, Petra, Stöhr, Heidi, De Roach, John N., Ayuso, Carmen, Roberts, Lisa, Weber, Bernhard H. F., Dhaenens, Claire Marie, Cremers, Frans P. M. |
بيانات النشر: | Lippincott Williams |
المجموعة: | CONICET Digital (Consejo Nacional de Investigaciones Científicas y Técnicas) |
مصطلحات موضوعية: | ABCA4, DEEP-INTRONIC VARIANTS, SMMIPS, STARGARDT DISEASE, STRUCTURAL VARIANTS, https://purl.org/becyt/ford/3.2, https://purl.org/becyt/ford/3 |
الوصف: | Purpose: Missing heritability in human diseases represents a major challenge, and this is particularly true for ABCA4-associated Stargardt disease (STGD1). We aimed to elucidate the genomic and transcriptomic variation in 1054 unsolved STGD and STGD-like probands. Methods: Sequencing of the complete 128-kb ABCA4 gene was performed using single-molecule molecular inversion probes (smMIPs), based on a semiautomated and cost-effective method. Structural variants (SVs) were identified using relative read coverage analyses and putative splice defects were studied using in vitro assays. Results: In 448 biallelic probands 14 known and 13 novel deep-intronic variants were found, resulting in pseudoexon (PE) insertions or exon elongations in 105 alleles. Intriguingly, intron 13 variants c.1938-621G>A and c.1938-514G>A resulted in dual PE insertions consisting of the same upstream, but different downstream PEs. The intron 44 variant c.6148-84A>T resulted in two PE insertions and flanking exon deletions. Eleven distinct large deletions were found, two of which contained small inverted segments. Uniparental isodisomy of chromosome 1 was identified in one proband. Conclusion: Deep sequencing of ABCA4 and midigene-based splice assays allowed the identification of SVs and causal deep-intronic variants in 25% of biallelic STGD1 cases, which represents a model study that can be applied to other inherited diseases. ; Fil: Khan, Mubeen. Radboud University Nijmegen Medical Centre; Países Bajos ; Fil: Cornelis, Stéphanie S. Radboud University Nijmegen Medical Centre; Países Bajos ; Fil: Del Pozo Valero, Marta. Hospital Universitario Fundación Jiménez Díaz; España. Radboud University Nijmegen Medical Centre; Países Bajos ; Fil: Whelan, Laura. Trinity College; Estados Unidos ; Fil: Runhart, Esmee H. Radboud University Nijmegen Medical Centre; Países Bajos ; Fil: Mishra, Ketan. Radboud University Nijmegen Medical Centre; Países Bajos ; Fil: Bults, Femke. Radboud University Nijmegen Medical Centre; Países Bajos ; Fil: AlSwaiti, ... |
نوع الوثيقة: | article in journal/newspaper |
وصف الملف: | application/pdf |
اللغة: | English |
تدمد: | 1098-3600 1530-0366 |
Relation: | info:eu-repo/semantics/altIdentifier/doi/; http://hdl.handle.net/11336/140677; Khan, Mubeen; Cornelis, Stéphanie S.; Del Pozo Valero, Marta; Whelan, Laura; Runhart, Esmee H.; et al.; Resolving the dark matter of ABCA4 for 1054 Stargardt disease probands through integrated genomics and transcriptomics; Lippincott Williams; Genetics In Medicine; 22; 7; 7-2020; 1235-1246; CONICET Digital; CONICET |
الاتاحة: | http://hdl.handle.net/11336/140677 |
Rights: | info:eu-repo/semantics/openAccess ; https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
رقم الانضمام: | edsbas.2DBC5583 |
قاعدة البيانات: | BASE |
تدمد: | 10983600 15300366 |
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