CRISPR, Genome Testing, and Direct Patient Care

Dr. Angela Scheuerle Editor-in-Chief of Molecular Syndromology, explains in our interview what inspires her in her specialization of medical genetics, how she can help patients, and what advice she has for researchers that wish to submit a paper to this journal.

Please tell us a little bit about yourself and your research interests.

I fell in love with genetics when I was 15 and I started my medical genetics fellowship in 1991 — right at the beginning of the Genome Project. That was back when it was possible to keep up with gene discoveries because it was one every couple of weeks. I boarded in clinical genetics and clinical molecular genetics. After a number of years in academic medicine and private practice, I joined the faculty at the University of Texas Southwestern Medical Center in 2014. My work now includes direct patient care, some teaching/resident and fellow training, and various research projects. The ongoing projects in which I’m involved are at the level of public health genetics and pharmaceutical use in pregnancy, looking at birth defects and patterns thereof across populations. I’m interested in syndrome definition and identification of recurrent but previously unrecognized patterns of birth defects.

How did you get into your field and what excites you the most about genetics?

I had known I wanted to be a clinical geneticist in high school, I think even before the job actually existed except in a few places. In 1988, when I graduated medical school, medical genetics was not yet a recognized specialty as it is now. I took the typical road — a pediatrics residency and then a genetics fellowship. It was during my fellowship that medical genetics “grew up” into a full medical specialty.

Since that first “aha” moment, I’ve thought of genetics as the way to learn the secret of a magic trick. Why are those peas round and yellow? How did this child come to have this condition? In 1983, HIV was identified by how it looked under an electron microscope. Now when there is a new epidemic we sequence the viral genome. Every new technology opens us up to new ways of understanding genetics (and of making clear what we don’t really know) and so we continue to learn how to make the rabbit appear in the hat.

What do you think will be the “hot topics” in genetics in 2022 and beyond?

Looking at the world in mid-2021 I’d like to think one of them will be RNA vaccines. Otherwise, in human genetics it will be treatments. The microRNA/small interfering RNA work is fascinating and I hope it goes somewhere. The invention or identification of medications targeting particular gene action in spinal muscular atrophy and achondroplasia, I think, will be paradigms for other treatments of that sort. Gene therapy has been around for three decades now without major successes, mostly because the process turns out to be so much more complex than expected. I will be surprised, albeit pleasantly, if CRISPR makes a difference quickly for non-hematologic conditions.

Serious ethical issues will also make up some of the ‘hottest’ topics, such as genomic testing of newborns and racial identification. Newborn genome testing is already being done under some research protocols and the UK recently announced a project to do whole genome sequencing and store genetic data from 200,000 clinically healthy newborns. We must also remain vigilant about the use of genetic information to identify racial identities, which raises all manner of significant ethical questions about how this information might be abused.

Why did you decide to become Editor-in-Chief of Molecular Syndromology?

I was contacted by Dr. Lisa Shafer, the previous North American Editor-in-Chief, about the position and was flattered that she thought of me. I’ve been an associate editor of two other moderately busy journals and was excited by the prospect. Genetics is a fast-moving field and I think it is important that the literature informs that. I would particularly like to support good work done by researchers who have limited access to publications.

What advice would you give to someone who is considering submitting to the journal for the first time?

It is important that the work be of real use to the reader. Genetics is an applied science, and the authors should consider how their information might benefit both the laboratory technician and the clinician. It can be helpful to have authors from both sides of the science on the paper. Each should think about what objective value the information would have if they could know it next week: would it make a measurable difference in their approach? For example, the report of a case with a novel variant in a gene known to cause the patient’s phenotype should be registered in one of the public databases but will not assist with diagnosis or testing of the next patient with that phenotype. On the other hand, if the novel variant is in a candidate gene, or causes pathology because of a previously un-defined mechanism, or changes the phenotype in such a way that the diagnosis would not be made clinically, that is very important.