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sequencing. In the ca se of patients w ith schizophrenia , structura l variants were found within misplaced or missing TA D boundaries, suggesting that TA D-affecting structura l variants may contribute to the disorder's development. Since semina l research published in 2012, scientists have recognized TADs as a type of 3D genomic structure, forming regions within the genome that assist with genomic commu- nications. These points of contact, a long with others, help to regulate gene expression in chromosomes. TADs in particular have boundaries to prevent domains from interacting with genetic materia l in neighboring genomic reg ions. W hen these bounda ries a re compromised, genes that would not commonly interact are able to do so. These interactions can affect gene expression, causing cancers, congenita l defects and developmenta l disorders. However, this study was the first to connect abnorma lities within TA D boundaries and the development of schizophrenia. To conduct this study, Szatkiewicz et al. received inter- national-collaboration-pooled funding from the National Institute of Mental Health and Sweden's SciLife Labs, as the high cost of whole-genome sequencing has prevented it from being used in more studies. Whole-genome sequencing was performed on 1,000 control subjects without schizophrenia and 1,165 patients with the disease, making this the largest known study of its kind in history. " We have applied for funding to carry out functiona l work with patient-derived cells in the near future," Szatkiewicz tells MD News. "Once funded, we will be able to obtain cells that carry those TAD-affecting mutations, differentiate them into relevant neurona l subtypes, and functiona lly characterize different neurons using genome technologies that can revea l the precise functiona l effects of these mutations." THE FUTURE OF GENOMICS IN MENTAL HEALTH The study's findings show promise for the future of under- standing the underlying biological mechanisms not only of schizophrenia but of mental illness in general. "Understanding the role of genomics in mental illness...will enable the development of more effective diagnosis [such as] genetic testing, and treatment [such as] optimizing treatment protocol, selecting effective drugs according to one's genetic makeup, and using gene editing tools to modify altered genome structures and restore proper function or target affected genes or their products," Szatkiewicz says. "Genetic testing will likely become more prevalent, and a genetic causal factor for mental illness may help reduce stigma and increase compassion for individuals." The ability to find effective treatment for schizophrenia could be especia lly revolutionar y for individua ls with the disorder. Untreated schizophrenia can be disabling to indi- vidua ls with the disorder, reducing their qua lity of life, but finding the best medication sometimes ta kes longer tha n patients or physicians would prefer. "Finding the right medication for mental illness sometimes involved [a] prolonged trial-and-error period," Szatkiewicz says. "Genetic testing will be able to help narrow down the options much more quickly." n " Whole-genome sequencing can potentially provide a more complete enumeration of etiological genetic variations and uncover novel variants previously undetectable using exome sequencing or single nucleotide polymorphism arrays." — JIN SZATKIEWICZ, PHD, ASSOCIATE PROFESSOR, DEPARTMENT OF GENETICS AND ADJUNCT ASSISTANT PROFESSOR, DEPARTMENT OF PSYCHIATRY AT THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL Schizophrenia 1 5 M D N E W S . C O M /// M D N E W S M i D - P E N N ■ 2 0 21