One of the major research goals of The Ehlers-Danlos Society (Society) is to identify and characterize gene(s) in which mutations lead to the hypermobile EDS (hEDS) phenotype. To this end the Society is funding research to directly identify genetic alterations in the exomes and genomes of affected individuals that could explain the clinical picture and, potentially, provide target genes for treatment. A complementary approach is to characterize the transcriptome of cells from individuals with hEDS to identify alterations in expression of individual genes or sets of genes that could directly explain or identify pathways of gene regulation that are disturbed. This type of approach can be used to identify alteration in the levels of expression of genes which might not be obvious candidates either from candidate gene approaches or the examination of sequence alteration in either the exome or the genome. This type of approach may also facilitate the identification of pathways that are affected that could explain phenotypic variation both within families and among individuals from different families.
The Ehlers-Danlos Society is requesting proposals to examine global gene expression (using RNA-Seq or other comparable and informative strategies) in cultured cells or affected tissues derived from individuals with hypermobile Ehlers-Danlos syndrome (hEDS) as defined by the 2017 diagnostic criteria and to identify alterations unique to this syndrome and shared among one or more sets of affected individuals. The study may also include a limb examining patients with hypermobile spectrum disorder (HSD) if a coherent set of eligibility requirements can define one or more subsets of individuals. There may be an advantage to study individuals whose exomes/genomes have been sequenced or from whom DNA is available and consented for such a study.
STUDY DESIGN REQUIREMENTS
- The study must include at least 20 participants with hEDS who meet the 2017 criteria.
- The study may include participants with HSD, with defined entry criteria.
- Each participant must also provide DNA with consent to perform whole-exome/genome sequencing.
The investigator should have experience with the performance and interpretation of gene expression studies and have appropriate bioinformatics tools available to characterize expression levels of genes relative to appropriate control samples, and to be able to identify sequence alterations that have clinical significance.
SUBMIT A PROPOSAL
Application deadline: August 31, 2019
Award Announcement: October 15, 2019
Funds Available: October 31, 2019
The Medical and Scientific Board of The Ehlers-Danlos Society (a committee of experts in basic and clinical research) will review each application. The NIH peer review study section model will be followed. Each proposal will receive a priority score based on the evaluation of the committee. Priority scores will be forwarded to The Ehlers-Danlos Society, where award decisions will be made based upon relative scientific merit ranking of the submitted grants, and on priorities of The Ehlers-Danlos Society. Grant awards are based on the approval of the Board of Directors. All applications will be held in the strictest confidence and all decisions by the Society are final.
Research Methods including bioinformatics pipelines and analysis
Timeline of Research
Biosketch for each professional involved in NIH format
Letters of collaboration (if needed)