Objective
Background: Mitral valve prolapse (MVP) is one of the most common valvular heart disorders. Twenty percent of MVP patients will develop severe complications, including congestive heart failure, endocarditis, atrial arrhythmias, embolic events and even sudden death. MVP is the most common cause of mitral regurgitation requiring surgical repair, however, very little is known about its etiology. MVP has a strong genetic background with significant heterogeneity. Previous genetic studies have shown that non-syndromic MVP can be caused by mutations in filamin A, and the applicant’s group has identified two additional genetic loci, MMVP2 and MMVP3, on chromosomes 11 and 13. In this study we propose to identify the gene for MMVP2 using next-generation sequencing analysis, and to analyze additional families to further define the molecular pathways that lead to the development of MVP.
Aims: The aims of this proposal are to 1) identify the gene for MMVP2 using next-generation sequencing and 2) identify MVP-causing mutations in families segregating the disease by whole-genome family-based linkage analysis, positional cloning and parallel sequencing.
Methods: A DNA library representing MMVP2 locus of 4 affected individuals was already prepared and will be sequenced. After sequencing we will validate potential mutation by replicating in nearly 200 familial and sporadic MVP cases. Newly recruited families segregating MVP will be queued for a whole-genome linkage analysis to identify MVP susceptibility loci. DNA of the targeted regions in affected individuals will be pooled and sequenced using next-generation parallel sequencing in search for sequence variation. The pathogenicity of sequence variations will be determined by verifying their segregation with disease in the pedigree, by assessing their effect on protein structure and expression using bioinformatic tools, and by comparing their frequency in cohorts of patients and controls.
Expected results and probable impl
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciences clinical medicine cardiology cardiovascular diseases cardiac arrhythmia
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics mutation
- natural sciences biological sciences genetics chromosomes
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
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.
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.
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.
FP7-PEOPLE-2010-RG
See other projects for this call
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.
Coordinator
91120 Jerusalem
Israel
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.