NIMH-funded study will assess 3q29 deletion syndrome, schizophrenia risk

Researchers at Emory University recently received a $3.1 million grant from the NIMH to study associations between 3q29 deletion syndrome and risk for schizophrenia and other neuropsychiatric disorders, such as intellectual disability, autism and anxiety.

“Because no other research team has worked on this syndrome, the mechanisms are not well understood,” study researcher Jennifer Mulle, PhD, of Emory University School of Medicine, said in a press release. “Our team of geneticists, molecular biologists and psychiatrists has deep expertise in evaluating neuropsychiatric phenotypes, which will allow us to create a set of rich behavioral and clinical variables associated with the biomaterials available through our 3q29 registry. In addition to advancing fundamental research, we hope to help families learn more about the syndrome and its behavioral and clinical manifestations, and potentially understand better ways to treat it.”

Mulle and colleagues will identify and quantify behavioral and clinical symptoms of 3q29 deletion in children and adults and establish a public repository of biomaterials from 3q29 deletion carriers at the Rutgers University Cell and DNA Repository.

Further, researchers plan to develop a neuronal model of 3q29 deletion syndrome using induced pluripotent stem cells (iPSC). Using iPSC technology will enable researchers to take blood or skin cells and reprogram them into a specific cell type that can then be characterized with molecular tools.

In addition, researchers will use iPSCs to produce two sets of cell lines from healthy controls with and without deleted 3q29 and CRISPR to conduct gene deletion so that the two cell lines will be isogenic. The iPSCs will be differentiated into neurons and researchers will compare molecular and cellular phenotypes in the neuronal cell lines with iPSC neurons from 3q29 deletion carriers with confirmed psychosis or prodromal symptoms.

“Rare variants have the potential to transform our understanding of disease. A rare genetic variant can reveal a general mechanism of disease and open a path to effective treatments. In order to unravel the biology of complex diseases, initial gene discovery must be followed by detailed functional studies, which is what our project aims to do,” study researcher Gary Basell, PhD, of Emory University School of Medicine, said in the release. “By combining the power of iPSC technology with DNA from affected individuals in the registry, our team hopes to define the core neurodevelopmental factors associated with the 3q29 deletion. We can ultimately translate this into a ‘disease in a dish’ platform that can be used for screening compounds to restore functionality.”