Project description
Hidden mutations in rare genomic diseases
Over 200 million people worldwide suffer from rare genomic diseases (RGDs), yet fewer than half receive a molecular diagnosis. This leaves millions navigating prolonged diagnostic odysseys, limiting opportunities for personalised care. Emerging research highlights the role of complex DNA mutations, specifically structural variations (SVs) and short tandem repeats (STRs), in many undiagnosed RGDs. These genetic changes, spanning multiple base pairs, remain poorly understood. Supported by the Marie Skłodowska-Curie Actions programme, the DETECT-SV-RD project addresses this challenge by analysing over 1 400 genomes using cutting-edge sequencing and optical genome mapping technologies. Overall, the project aims to uncover SVs and STRs, even in complex genomic regions, and integrate findings with clinical data to improve diagnosis rates.
Objective
Rare Genomic Diseases (RGDs) affect >200 million individuals globally, however less than half of patients receive a molecular diagnosis, forcing millions into year-long diagnostic odysseys, and limiting the possibilities for personalized care. New studies suggest that forms of DNA mutation affecting many base pairs of at once, so-called 'Structural Variations' (SVs) and 'Short Tandem Repeats' (STRs) may play a dominant role in the biological underpinnings of many undiagnosed RGDs.
The DETECT-SV-RD project will utilise one of the largest-to-date RD-patient datasets, containing >1,400 genomes obtained by latest long-read sequencing and optical genome mapping technologies, to identify the full spectrum of SVs and better understand their impact on disease formation. To achieve this, a new computational workflow for detecting SVs will be developed, which will have a special focus on mutations that occur in the most complex, repeat-rich regions of the human genome. Using these technological advances, SVs and STRs will be identified across all patients, and carefully characterized in terms of their rarity, the properties of their breakpoints and likely biological formation mechanisms. Lastly, these insights will be combined with orthogonal 'omics' and phenotypic data to gain new insights into the underlying biology of rare diseases. In collaboration with the diagnostic department at Radboudumc, new genetic tests for SVs and STRs will finally be implemented to improve patient care.
The project will, for the first time, assess the effect of SVs and STRs even in complex genomic regions comprehensively and provide an estimate for their involvement in the formation of RDs in general, as well as likely a better understanding of previously undiagnosed RDs. The project will thus contribute to improving the rate of correct RD diagnoses in the future, providing substantial emotional and physical relief to affected patients and their families.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences genetics mutation
- natural sciences biological sciences genetics genomes
You need to log in or register to use this function
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
-
HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
See all projects funded under this programme
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
See all projects funded under this funding scheme
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2023-PF-01
See all projects funded under this callCoordinator
Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
6525 GA Nijmegen
Netherlands
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.