In a new study, researchers performed a global genome-wide analysis and showed that DNA regions with short repeat units, called Short Tandem Repeats (STRs), are key players regulating gene expression involved in several diseases, including Crohn’s disease. The study, “Abundant contribution of short tandem repeats to gene expression variation in humans,” appeared in the advance online publication section of Nature Genetics’s journal.
Dr. Yaniv Erlich, study lead author and assistant professor of computer science at Columbia Engineering, a member of Columbia’s Data Science Institute, and member of the New York Genome Center, said in a press release, “Our work expands the repertoire of functional genetic elements. We expect our findings will lead to a better understanding of disease mechanisms and perhaps eventually help to identify new drug targets.”
Differences in the DNA’s sequence is what makes the DNA signature from each of us unique. These genomic variants are, as Dr. Erlich explained, “like spelling errors in different flavors.” While the most common studied genetic variants are SNPs (single nucleotide polymorphisms), Dr. Erlich’s team focused on STRs, DNA regions with short repeat units — for an easier understanding, the word stutter with STRs would become stututututututter.
For a long time STRs were not considered important, and commonly referred to as “noise.” Now, the research team, using a complex algorithm of statistical genetic and integrative genomics analyses, showed that STRs can modulate gene expression, either enhancing or decreasing it, therefore representing a mechanism of fine-tuning. Researchers identified that approximately 10% to 15% of our genetic differences (in terms of gene expression ) are actually explained by STRs.
With this newly discovered role in mind, Dr. Erlich renamed these specific STRs as eSTRs, or expression STRs. Most importantly, the research team discovered that eSTRs can be associated with a varied range of diseases, including Crohn’s disease and high blood pressure, as well as with different metabolites.
In future studies, the team will try to understand eSTRs molecular mechanisms and how they translated into disease. “We’ve known that STRs are known to play a role in these diseases, but no one has ever conducted a genome-wide scan to find their effect on complex traits. If we want to do personalized medicine, we really need to understand every part of the genome, including repeat elements — there’s a lot of exciting biology ahead,” concluded Dr. Erlich.