The 3q29 Project, led by Dr. Jennifer Mulle at the Robert Wood Johnson School of Medicine at Rutgers University, is focused on understanding the phenotypic spectrum, molecular mechanism, and natural history of the 3q29 deletion and 3q29 duplication syndromes.
To meet these goals, we pursue scientific investigation across the research spectrum, from basic science to clinical translational work. In collaboration with the G2MH Network, our latest studies will accomplish the following:
Aim 1: To determine and quantify the behavioral and clinical phenotype in 200 probands with 3q29 deletion syndrome.
Using our validated remote phenotyping protocol, we will characterize 200 new study subjects, and identify the full phenotypic spectrum, sex-dependent phenotypic risks and significant comorbid relationships in 3q29 deletion syndrome. We will also quantify parental phenotypes along four dimensions: cognitive ability, social behavior, executive function, and symptoms of psychosis including sub-threshold psychosis. We will contextualize the burden of illness in 3q29 deletion syndrome relative to departure from mid-parental phenotype, to clarify the range of phenotypic heterogeneity in 3q29 deletion syndrome.
Aim 2: To test the hypothesis that genetic background influences the 3q29 deletion phenotype.
We will assess the contribution of polygenic background to key phenotypes including cognitive ability, executive function, and psychosis. We will also perform whole genome sequencing to identify the contribution of second-site rare variants to phenotypic heterogeneity.
Aim 3: To compare phenotypes and risk modifiers between 3q29 deletion syndrome and >2,000 samples from other genomic disorders through a large collaborative network.
In collaboration with the NIMH-sponsored Genes 2 Mental Health Network, we will compare the phenotypic spectrum and risk modifiers of 3q29 deletion syndrome with other genomic disorders associated with neurodevelopmental and neuropsychiatric disorders, including 22q11.2 deletion and duplication, 16p11 deletion and duplication, 1q21 deletion, and others.
Impact: Upon completing this project, we will have a rich and nuanced understanding of 3q29 deletion phenotypes; we will articulate and quantify factors contributing to the variance in phenotypic severity; and we will produce a side-by-side comparison of the 3q29 deletion with other CNV disorders. These data will pave the way toward our long-term goal: harmonized studies of convergent biology among rare genetic disorders.