This project will be carried out by a research team in the Genetics, Functional Genomics and Biotechnology (Inserm UMR 1078) at Brest in Brittany in France. Collaborators associated to this project bring together overlapping and complementary expertise and competences in different fields (scientists, geneticists, biostatisticians, epidemiologists and bioinformaticians.
One of the challenges facing medicine is to understand the fine regulation of gene expression. The human genome sequencing program has enabled us to more access this, dissecting the fine mechanisms of gene expression to gain a better understanding of the pathophysiology of disease. Genetic diseases are mainly associated with variations in coding sequences. However, many pathologies are due to abnormal gene expression, following the alteration of one of its regulatory elements. The terms 'cis-ruption disorder' or 'enhanceropathies' describe pathologies originating from dysfunction of a cis-regulatory element (CRE). CREs are bound by tissue-specific transcription factors, enabling regulation in time, space or a specific cell type. These cis-regulatory sequences have different characteristics depending on their activity. Four types of CREs have been described: enhancers, silencers, insulators and certain promoters. 8% of the genome is covered by candidate CREs, which underlines the importance of chromatin conformation signatures and understanding genome regulatory elements to predict their potential pathogenic roles.
Cystic fibrosis is a disease that affects many people, but it is highly heterogeneous from a genetic and clinical point of view. Since the involvement of the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene in cystic fibrosis was discovered, more than 2,100 variations have been identified. However, this does not explain the variation in the severity of symptoms observed in patients. Cystic fibrosis is a multi-organ pathology, and its effects vary from patient to patient. To better characterize the pathology and regulation of the CFTR gene, we have described regulatory models in different tissues with about twenty CFTR CREs and cCREs.
We now need to look for cis-regulatory variants in these elements to determine their real clinical impact.
The study will analyse genetic and phenotypic data from cystic fibrosis patients enrolled in the American Cystic Fibrosis Foundation (CFF) Registry.
Access to this data will be used to search for variants in twenty CREs that have been identified as being involved in the regulation of the CFTR gene. The variants will be retrieved using bioinformatics and then biostatistical approaches will be used to identify variants that are significantly different from the general population. Epidemiological studies will then be used to correlate these variants with phenotypic traits. The aim of this study will be to associate cis-regulatory variants with extreme CF phenotypes. Survival and haplotypic association analyses will also be performed
The legal basis for processing is public interest mission. Personal health data is processed only for research purposes.
Data provided by the Cystic Fibrosis Foundation (source) are analysed by Inserm (data recipient). Only declared investigators (see list below) will have access to this data. This data will be kept for 3 years in an active database on servers in Brest. None of this individual data will be archived in France.
Only the following genetic and phenotypic data are requested : data sequencing of chromosome 7, identification data (identifier specifically assigned for VAINCRE-CFTR research), Health data (about your diagnosis, clinical exams, etc.)
VAINCRE-CFTR research will plan to last 6 years.
The first part of the research consists to analysed all your individual genetic and phenotypic data provided by the Cystic Fibrosis Foundation and will last 3 years.
The second part, which last 3 years too, will be dedicated to analysis of the first part results, with comparison and exploration of aggregated data.
Your individual data retention period by Inserm is 3 years. At the end of this period your individual data will be deleted from our servers, as requested by Cystic Fibrosis Foundation.
The VAINCRE-CFTR research has been assessed by an independent ethics committee (IEC), Comité d'évaluation éthique de l'Inserm.
For more information and to exercise lawful rights (to be informed, of access, of object, to request rectification, restriction of the processing and erasure of your personnal data), patients can contact Inserm, at any time, by the following means:
Patients, can also contact Inserm Data Protection officer (DPO), at any time, by:
The VAINCRE-CFTR research is carried out in compliance with the European General Data Protection Regulation (GDPR) and the regulations of French data protection authority (Cnil).
You also have the right to file a complaint with the Cnil.
* If patient exercises his/her erasure lawful rights, the data will not be included in the analysis work unless the analysis has already begun.
The list of investigators (in alphabetical order) declared on VAINCRE-CFTR research in the 1078 Inserm' research unit in Brest.
| Last name | First name | Role |
|---|---|---|
| BLOTAS | Clara | Investigator |
| DERRIEN | Julie | Investigator |
| GENIN | Emmanuelle | Investigator |
| L'HOSTIS | Carine | Investigator |
| LUDWIG | Thomas | Investigator/Servers administrator |
| MOISAN | Stéphanie | Scientific coordinator |
| SCOTET | Virginie | Investigator |