Posted By: Sarah Ratzel, PhD, Science Editor, AJHG
Each month, the editors of The American Journal of Human Genetics interview an author of a recently published paper. This month, we check in with Josh Motelow to discuss his paper, “Sub-genic intolerance, ClinVar, and the epilepsies: A whole-exome sequencing study of 29,165 individuals”.
AJHG: What caused you to start working on this project?
JM: As a pediatric critical care medicine fellow at Columbia and physician-scientist, I am always looking for the best way to blend my interests in science with my clinical work to help my patients. My PhD work with Hal Blumenfeld focused on understand epilepsy networks and the mechanism by which a local seizure could have remote effects. The project with Dr. Goldstein gave me two opportunities. First, it allowed me the chance to explore epilepsy pathogenesis closer to its roots. I hope the paper adds knowledge for the epilepsy community. Second, I was able to learn human genetics from Dr. Goldstein, which has been a wonderful experience.
AJHG: What about this paper most excites you?
JM: I am extremely grateful to all of the individuals with epilepsy and their families who have contributed to this work. It is always exciting to partner with a community that is so engaged. The most exciting thing is to use the training I’ve received to continue to chip away at the understanding of a disease and ultimately work towards a cure.
AJHG: Thinking about the bigger picture, what implications do you see from this work for the larger human genetics community?
JM: First, this work adds to the body of literature that sub-genic intolerance is crucial to interpreting missense variants. Second, I think we provide evidence that sub-genic intolerance can likely play a role in prognostication and diagnostic interpretation although much work needs to be done on that front. And finally, it seems that there are more epilepsy-risk genes to be discovered, especially among genetic generalized epilepsy and non-acquired focal epilepsy.
AJHG: What advice do you have for trainees/young scientists?
JM: As awkward as it can be, go outside your comfort zone!
AJHG: And for fun, tell us something about your life outside of the lab.
JM: When I’m not working in the hospital, I can usually be found on the playground chasing (or getting chased by) my family!
Joshua Motelow, MD, PhD is a clinical fellow in the Division of Pediatric Critical Care and a postdoctoral fellow at the Institute for Genomic Medicine at the Columbia University Irving Medical Center.