Abstract
Benjamin W. Darbro, MD, PhD (he/him)
Associate Professor, Stead Family
Department of Pediatrics
Director, Shivanand R. Patil Cytogenetics and Molecular Laboratory
Associate Director, Iowa Institute of Human Genetics
University of Iowa
Our laboratory Initiated genomic scale testing at the University of Iowa with the goal of consolidating multiple tests (i.e., single gene or panel testing) onto one standardized platform. Through whole exome sequencing (WES) and whole genome sequencing (WGS) we could simplify the genomic testing processes and accomplish the same clinical testing outcomes but with more comprehensive information and improvements in diagnostic yield. Originally intended to provide confirmatory DNA sequencing for our Newborn Screening Program, our scope has extended to provide timely diagnostic genetic testing for both acutely ill newborns in the NICU as well as outpatients seeking an end to their diagnostic odyssey. We have been able to eliminate logistical hurdles that come with outsourcing comprehensive testing and have enabled our clinical colleagues to understand the underlying cause of disease earlier and thus pursue the most appropriate course of clinical management.
I wouldn't say a specific case, but several cases over many years combined with the increasing number of publications demonstrating the clear clinical utility of genomic scale sequencing. There were so many previous situations in which this technology could have been very impactful. Soon WES/WGS, as a first line genetics diagnostic test, will become the standard of care and we need to be able to provide that to the patients of Iowa.
In short, scope and cost. WES/WGS give you more for less and geneticists like to cast a wide net. Practically speaking, not all patients walk into the clinic having “read the textbook”. Jean- Martin Charcot once said, “Clinical medicine is first and foremost the study of the difficult aspects and complexities of diseases. When a patient calls on you, he is under no obligation to have a simple disease just to please you.” Nowhere is this more true than in clinical genetics. WES/WGS is one of our greatest tools for overcoming the heterogeneity of genetic disease, and it can do this in a timely, cost-effective fashion.
With great genomic data, comes great analytic and interpretative responsibility. Validating a new clinical test is always a large effort and WES/WGS takes that to the next level. Best advice I could give is to have a clear procedure to follow for the validation, reduce efforts in other areas to focus on this one, work with established vendors and software (preferably ones that will work with you collaboratively), and have an air-tight business plan for your department administrators.
This is a very important question and one to which I feel the answer is still being developed. Solutions will need to be novel and come from collaborations between clinical laboratorians, test ordering healthcare providers, insurance payers, and patient advocates. It is unlikely one solution will be universal, thus each institution must understand their own reasons for inequity of genetic testing. We are in the early stages of better defining the problem so that we can develop robust solutions to address it.
