STRIPE · Structural variants impacting peripheral neurodegeneration
Horizon Europe — Marie Skłodowska-Curie Actions
- Duration
- 2023-10-01 → 2025-09-30
- EU contribution
- €191,760
- Participants
- 1
- Scheme
- HORIZON-TMA-MSCA-PF-EF
Lines connect the coordinator with its partners.
Results in brief
Structural variants impacting peripheral neurodegeneration
Inherited peripheral neuropathies are rare neurological conditions that cause progressive nerve dysfunction, muscle wasting, walking problems, and lifelong disability. Despite advances in genetic testing, many patients still remain without a genetic diagnosis, often for years. This "diagnostic odyssey" delays access to specialist care and prevents families from receiving accurate genetic counselling. One major reason for the low diagnostic rate is that standard short-read DNA sequencing technologies are unable to detect certain types of genetic variation. This project sets out to address this challenge by applying long-read genome sequencing, an emerging technology capable of reading continuous stretches of DNA much longer than conventional methods. This technology provides a more complete view of the genome and has the potential to uncover disease-causing genetic defects that were previously unrecognized. The overall objectives are to apply nanopore genome sequencing to individuals with unsolved inherited neuropathies to identify candidate disease-causing genetic variants, determine how these variants affect gene function, and to establish novel gene-disease relationships.
Data: CORDIS, © European Union
Project objective
Many Mendelian diseases have benefited from next-generation sequencing (NGS) technologies for gene discovery and the establishment of molecular diagnosis. However, the technical limitations of NGS pose a challenge for identifying mutational mechanisms in genomic regions impenetrable by these technologies. I hypothesize that complex genomic rearrangements called structural variants in these loci can explain a significant proportion of missing heritability in many monogenic diseases. To this end, I propose to investigate the involvement of structural variants in the pathogenesis of Charcot-Marie-Tooth disease (CMT), the most common genetic affliction of the peripheral nervous system. I will utilize long-read Nanopore sequencing in a unique patient cohort to look for potentially disease-causing structural variants. I will then adopt genetic and functional in vitro and in vivo approaches to characterize the identified genomic variants and ascertain the associated functional genes that most likely underlie molecular pathology. The findings of my pioneering study will highlight the contribution of structural variants in peripheral neurodegeneration, discover non-conventional mutational mechanisms long overlooked by state-of-the-art technologies, and deliver in vivo models that might provide clues for therapeutic approaches for peripheral nerve disorders with common etiology.
Original text from CORDIS.
Participants
- VIB VZW · ZWIJNAARDE - GENTCoordinatorBelgium
Links
- View on CORDIS
- DOI: 10.3030/101108071
- https://ec.europa.eu/research/participants/documents/downloadPublic?documentIds=080166e50c418c38&appId=PPGMS
- https://ec.europa.eu/research/participants/documents/downloadPublic?documentIds=080166e521696a10&appId=PPGMS
Data: CORDIS, © European Union