P724: Expanding the matched annotation from NCBI and EMBL-EBI (MANE) dataset to include MANE Select for non-coding genes
Focusing on a set of 10 patients for whom there was high confidence in a small number of candidate genes, we used patient blood samples or fibroblasts to generate cDNA, PCR for genes of interest and generate full length reads using Oxford Nanopore Technologies single molecule sequencing.Results: Using this approach we identified probable pathogenic splicing events in two patient samples.We used not only existing transcriptomic annotations, but also publicly available short-and long-read sequencing data from control individuals to determine the rarity of the events detected.Furthermore, by enabling the prediction of both ORFs and protein structures, the availability of full-length reads greatly increased our ability to identify events expected to disrupt gene function rapidly.Conclusion: Taken together, our findings suggest that targeted long-read RNA-sequencing in patients who remain undiagnosed following extensive testing could be an important tool particularly when a treatable genetic diagnosis is being considered.
Authors
- Anjana Vatsan
- Françoise Thibaud-Nissen
- Shashikant Pujar (ORCID: https://orcid.org/0000-0001-7132-5513)
- Andrew C. Berry (ORCID: https://orcid.org/0000-0001-8952-6559)
- Ruth Bennett
- Vamsi K. Kodali (ORCID: https://orcid.org/0000-0001-8941-9761)
- Terence D. Murphy (ORCID: https://orcid.org/0000-0001-9311-9745)
- Sanjida Rangwala
- Alex Astashyn
- Adam Frankish (ORCID: https://orcid.org/0000-0002-4333-628X)
- David Webb (ORCID: https://orcid.org/0000-0003-4243-4002)
- Claire Davidson (ORCID: https://orcid.org/0000-0002-4910-8202)
- Eric Cox (ORCID: https://orcid.org/0000-0001-7691-4835)
- Jonathan M. Mudge (ORCID: https://orcid.org/0000-0003-4789-7495)
- Kelly M. McGarvey (ORCID: https://orcid.org/0009-0002-1055-996X)
- Mallory Freeberg (ORCID: https://orcid.org/0000-0003-2949-3921)
- Vinita Joardar (ORCID: https://orcid.org/0000-0001-9018-3151)
- Craig Wallin
- Tamara Goldfarb
- Matthew P. Hardy (ORCID: https://orcid.org/0000-0001-6420-1715)
- Diana Haddad
- Olga Ermolaeva
- Toby Hunt (ORCID: https://orcid.org/0000-0001-8377-0841)
- Jane Loveland (ORCID: https://orcid.org/0000-0002-7669-2934)
- Reham Fatima (ORCID: https://orcid.org/0000-0002-9914-4893)
- José Antonio González (ORCID: https://orcid.org/0000-0003-2751-7555)
- Michael Murphy (ORCID: https://orcid.org/0009-0004-9496-5811)
- Michael Kay
- J.D. Jackson
Institutions
- European Bioinformatics Institute (GB)
- National Center for Biotechnology Information (US)
Publication Details
- Journal
- Genetics in Medicine Open
- Published
- 2025-01-01
- DOI
- https://doi.org/10.1016/j.gimo.2025.103093
- Primary Topic
- Molecular Biology Techniques and Applications
- Type
- article
- Field-Weighted Citation Impact
- 0.00