> Detailanzeige

Bonetti, Gabriele; Cozza, William; Bernini, Andrea; Kaftalli, Jurgen; Mareso, Chiara; Cristofoli, Francesca; Medori, Maria Chiara; Colombo, Leonardo; Martella, Salvatore; Staurenghi, Giovanni; Salvetti, Anna Paola; Falsini, Benedetto; Placidi, Giorgio; Attanasio, Marcella; Pertile, Grazia; Bengala, Mario; Bosello, Francesca; Petracca, Antonio; D’Esposito, Fabiana; Toschi, Benedetta; Lanzetta, Paolo; Ricci, Federico; Viola, Francesco; Marceddu, Giuseppe;

Towards a Long-Read Sequencing Approach for the Molecular Diagnosis of RPGRORF15 Genetic Variants

Literatur-
verwaltung

Zur
Merkliste

Lösche von
Merkliste

Per Whatsapp teilen

Schließen

Merkliste



Sie können Bookmarks mittels Listen verwalten, loggen Sie sich dafür bitte in Ihr SLUB Benutzerkonto ein.
  • Medientyp: E-Artikel
  • Titel: Towards a Long-Read Sequencing Approach for the Molecular Diagnosis of RPGRORF15 Genetic Variants
  • Beteiligte: Bonetti, Gabriele; Cozza, William; Bernini, Andrea; Kaftalli, Jurgen; Mareso, Chiara; Cristofoli, Francesca; Medori, Maria Chiara; Colombo, Leonardo; Martella, Salvatore; Staurenghi, Giovanni; Salvetti, Anna Paola; Falsini, Benedetto; Placidi, Giorgio; Attanasio, Marcella; Pertile, Grazia; Bengala, Mario; Bosello, Francesca; Petracca, Antonio; D’Esposito, Fabiana; Toschi, Benedetta; Lanzetta, Paolo; Ricci, Federico; Viola, Francesco; Marceddu, Giuseppe;
  • Erschienen: MDPI AG, 2023
  • Erschienen in: International Journal of Molecular Sciences
  • Sprache: Englisch
  • DOI: 10.3390/ijms242316881
  • ISSN: 1422-0067
  • Schlagwörter: Inorganic Chemistry ; Organic Chemistry ; Physical and Theoretical Chemistry ; Computer Science Applications ; Spectroscopy ; Molecular Biology ; General Medicine ; Catalysis
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:p>Sequencing of the low-complexity ORF15 exon of RPGR, a gene correlated with retinitis pigmentosa and cone dystrophy, is difficult to achieve with NGS and Sanger sequencing. False results could lead to the inaccurate annotation of genetic variants in dbSNP and ClinVar databases, tools on which HGMD and Ensembl rely, finally resulting in incorrect genetic variants interpretation. This paper aims to propose PacBio sequencing as a feasible method to correctly detect genetic variants in low-complexity regions, such as the ORF15 exon of RPGR, and interpret their pathogenicity by structural studies. Biological samples from 75 patients affected by retinitis pigmentosa or cone dystrophy were analyzed with NGS and repeated with PacBio. The results showed that NGS has a low coverage of the ORF15 region, while PacBio was able to sequence the region of interest and detect eight genetic variants, of which four are likely pathogenic. Furthermore, molecular modeling and dynamics of the RPGR Glu-Gly repeats binding to TTLL5 allowed for the structural evaluation of the variants, providing a way to predict their pathogenicity. Therefore, we propose PacBio sequencing as a standard procedure in diagnostic research for sequencing low-complexity regions such as RPGRORF15, aiding in the correct annotation of genetic variants in online databases.</jats:p>
  • Zugangsstatus: Freier Zugang