Now in Print is a series highlighting recent publications by StatGen’s members. If you want to learn more about a particular article or researcher, please contact us at email@example.com.
Critical information about possible genetic causes of disease lies in the non-coding regions of the genome; however, implicating mutations falling in these regions as disease-causing culprits has been a challenge for researchers. A novel method, Orion, has been developed to identify non-coding regions that are depleted of genetic variation, as these regions are likely to be intolerant to mutations. Consequently, mutations occurring in these regions are more likely to result in disease.
StatGen member and recent Duke PhD graduate, Ayal Gussow, PhD, further defines this method and how it can be used to prioritize mutations and ultimately identify pathogenic variation in PLOS ONE article, “Detecting Regions of the Human Non-Coding Genome that are Intolerant to Variation Using Population Genetics.” A web interface for accessing the scores is available at http://www.genomic-orion.org/.
What does this method accomplish?
[AG]: This method provides a way for researchers to quantitatively assess whether mutations falling in the non-coding portions of the human genome are likely to result in disease.
Why is it significant for the field?
[AG]: Though it is known that mutations in the non-coding regions of the genome can cause disease, it is notoriously difficult to detect pathogenic mutations falling in these regions. As a result, researchers often end up ignoring non-coding mutations in disease studies, even though those very mutations may be driving the disease. The Orion methodology provides a mechanism through which medical genetics researchers can assess the non-coding regions of the genome, consequently advancing our ability to detect disease-causing genetic mutations in patients. In addition, as the Orion method was constructed solely based on human data, it can be used in conjunction with sequence data from other species to provide insight on the portions of the genome that are uniquely important to humans.
What are the next steps to further explore this topic?
[AG]: An evident and important next step is to incorporate Orion in the analysis of patients’ sequence data in order to aid in the discovery of causal mutations in the non-coding portion of the genome. On a broader scale, we can use the results of this study to explore the biology of the non-coding genome in-depth, so as to better understand the biological roles and functions of the non-coding regions of the human genome.
Gussow graduated from Duke’s Computational Biology and Bioinformatics PhD program in 2016 and is currently a Postdoctoral Fellow at the NIH in Bethesda, MD.
In addition to Gussow, authors on this paper include Brett R. Copeland, Ryan S. Dhindsa, Quanli Wang, Slavé Petrovski, William H. Majoros, Andrew S. Allen and David B. Goldstein.
To learn more about Orion or how to collaborate, please contact StatGen at firstname.lastname@example.org.
Gussow AB, Copeland BR, Dhindsa RS, Wang Q, Petrovski S, Majoros WH, Allen AS, Goldstein DB. (2017) “Orion: Detecting Regions of the Human Non-Coding Genome that are Intolerant to Variation Using Population Genetics.” PLOS ONE 12(8): e0181604. https://doi.org/10.1371/journal.pone.0181604