DBGen second anniversary and summary of the year

DBGen Ocular Genomics is a spin-off of the University of Barcelona specialized in the genetic diagnosis of hereditary eye disorders. It was founded in January 2018 by Roser Gonzàlez-Duarte and Gemma Marfany, both senior scientists focussed in human molecular genetics, particularly in the genetic basis of ocular disorders. DBGen Ocular Genomics aims to provide an accurate genetic diagnosis to guide and confirm the clinical diagnosis, establish a reliable prognosis, define the type of inheritance and allow genetic counselling. Genetic diagnosis is also essential to access the first approved gene therapy (Luxturna) and others now in advance phase clinical trials. The activity of DBGen relies on a team with over 25 years experience in genetic research of inherited retinal dystrophies.

DBGen Ocular Genomics would like to share with you the main milestones achieved along 2019.

DBGen advances in genetic diagnosis

This year, DBGen has presented the new version of the Complete Panel of Retinal Dystrophies and Other Eye Diseases, which includes 14 new genes. Similarly, the number of genes in the following panels has been increased: Retinitis Pigmentosa Panel, Macular Dystrophies and Stargardt Disease Panel, Bardet-Biedl Syndrome Panel, Usher Syndrome Panel, Optic Atrophy Panel.

Additionally, DBGen has opened the range of bioinformatic analysis and integrated novel methodologies to identify “hidden” mutations in non-coding regions. Besides, routine functional analyses have been implemented in the lab to assess the pathogenic effects of novel variants and increase the quality and yield of the genetic diagnosis

Next year, a third genetic diagnostic strategy, whole genome sequencing (WGS), will be added to the two main strategies now in use, whole exome sequencing (WES) and gene panels. Genome sequencing is particularly suitable in recessive cases to identify the missing second pathogenic allele, and to characterize genomic rearrangements and large deletions/duplications in large genes responsible for inherited eye disorders, otherwise undetectable by WES.

Our team

The DBGen team gathers scientists specialised in human genetics with a deep knowledge on the molecular basis of hereditary visual disorders. The team has expanded this year with the incorporation of two new members:

Laia Carreté, PhD in bioinformatics from the Pompeu Fabra University with advanced knowledge in data analysis and deep understanding on next-generation DNA sequencing techniques.

Vasileious Toulis, predoctoral researcher at the University of Barcelona, who carries out a thesis on animal models of ocular disorders and will be involved in the functional studies of novel genetic variants to improve the quality and yield of genetic diagnosis.

Research and publications

This year, the DBGen team has participated in several final degree and master’s thesis projects. Specifically, two final degree projects and one master’s thesis project.

• Sofía Jiménez Ochoa (2019). Optimization of genetic diagnosis of inherited retinal dystrophies: assessment of functional assays for the identification of mutations in intronic regions. Supervisor: Gemma Marfany (TFG).
• Mariona Costa Llamas (2019). Optimització del diagnòstic de malalties hereditàries de la retina: Detecció de CNVs en els gens OPN1LW i OPN1MW. Supervisors: Gemma Marfany & Marta de Castro-Miró (TFG).
• Luz Vianney Cortés González (2019). Estudio funcional de dos variantes nuevas en regiones intrónicas del gen POC1B en un paciente mexicano con distrofia de conos y bastones. Supervised by: Roser Gonzàlez Duarte i Rebeca Valero. (TFM)

Scientific publications:

1. Trigueros, S.; Domènech, E.B.; Toulis, V.; Marfany, G.In vitro gene delivery in retinal pigment epithelium cells by plasmid DNA-wrapped gold nanoparticles. 2019. Genes. 10, pp. 289. DOI: https://doi.org/10.3390/genes10040289
2. Bolinches-Amorós, A.; León, M.; del Buey Furió, V.; Marfany, G.; Gonzàlez-Duarte, R.; Erceg, S.; Lukovic, D. Generation of an iPSC line from a retinitis pigmentosa patient carrying a homozygous mutation in CERKL and a healthy sibling. 2019. Stem Cell Research. 38, pp. 101455.
3. Valero, R.; de Castro-Miró, M.; Jiménez-Ochoa, S.; Rodríguez-Ezcurra, J.J.; Marfany, G.; Gonzàlez-Duarte, R. Aberrant Splicing Events Associated to CDH23 Noncanonical Splice Site Mutations in a Proband with Atypical Usher Syndrome 1.2019.  Genes. 10, pp. 732.  DOI: https://doi.org/10.3390/genes10100732
4. Arenas-Galnares, R.; Castillo-Lara, S.; Toulis, V.; Boloc, D.; Gonzàlez-Duarte, R.; Marfany, G.; Abril, J.F. RPGeNet v2.0: expanding the universe of retinal disease gene interactions network. Database: The Journal of Biological Databases and Curation.  2019. DOI: https://doi.org/10.1093/database/baz120
5. Esquerdo-Barragán, M.; Brooks, MJ.; Toulis, V.; Swaroop, A.; Marfany, G. Expression of Deubiquitinating Enzyme Genes in the Developing Mammal Retina. 2019. Mol. Vis. 25: 800-813.

Participation in meetings and other events

DBGen team members have attended attended numerous scientific events presenting the research advances in lectures and seminars. They are highlighted below.

International events:

• Association for Research in Vision and Ophthalmology (ARVO) 2019 Annual Meeting (Vancouver, Canada)
• XXXIV American Ophthalmology Association (PAAO) Meeting (Cancun, Mexico)
• 42º SIMASP (São Paulo, Brazil)
• 8th International IVIRMA Congress (Palma de Mallorca, Spain)

Spanish events:

• 50º Catalan Society of Ophthalmology Congress (Barcelona, Spain)
• 3rd Catalan Interhospital Meeting on Genetics
• XIII Seminar on the universal declaration on bioethics and human rights of UNESCO in relation to the Oviedo Convention: ‘Gene editing, bioethics and responsibility’ (Barcelona, Spain)
• XII CIBERER Annual Meeting (El Escorial, Spain)
• II National Retina Murcia Congress (Murcia, Spain)
• CNG2019 – ‘Gene editing’, National Genetics Course, Spanish Genetics Society (Miraflores, Spain)
• Expert Patients and Researchers, 3 ed. EURORDIS Summer School Spanish Edition (Castelldefels, Spain)

Awards

Finally, the work of DBGen has been recognized during this year by being shorlisted as a finalist to the Innovatia 8.3 award (2019) to the best companies created with the support of universities and led by women, awarded by the Spanish Women’s Institute and the University of Santiago de Compostela.

External Quality Assessment

In 2019, DBGen has participated in the first external quality assessment (EQA) program dedicated to inherited retinal disorders, organized by Genomics Quality Assessment (GenQA), a member of the UK NEQAS consortium, providing external quality assessment of genetic diagnostic laboratories worldwide. In this first edition of IRD EQA (2019 Retinal Disorders), DBGen has passed all three tests satisfactorily.