Yaniv Erlich. Photo: Jared Leeds.

A new article published online in Nature Genetics reports that short tandem repeats, a class of genetic alterations in which short motifs of nucleotide base pairs occur multiple times in a row, play a role in modulating gene expression. Leading the study was Yaniv Erlich, an assistant professor in the Columbia University Department of Computer Science and core member of the New York Genome Center who recently joined the Center for Computational Biology and Bioinformatics.

As an article in Columbia Engineering explains, the findings reveal a new class of genome regulation.

Erlich’s study looked at Short Tandem Repeats (STRs), variants that create what look like typos: stutter vs. stututututututter. Most researchers, assuming that STRs were neutral, dismissed them as not important. In addition, these variants are extremely hard to study. “They look so different to analysis algorithms,” Erlich notes, “that they just usually classify them as noise and skip these positions.”

Erlich used a multitude of statistical genetic and integrative genomics analyses to reveal that STRs have a function: they act like springs or knobs that can expand and contract, and fine-tune the nearby gene expression. Different lengths correspond to different tensions of the spring and can control gene expression and disease traits. He is calling these variants eSTRs, or expression STRs, to note that they regulate gene expression. He and his team also discovered that these eSTRs can be associated with a range of conditions including Crohn's diseases, high blood pressure, and a range of metabolites. These eSTRs explain on average 10 to 15% of the genetic differences of gene expression between individuals.

“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,” Erlich adds. “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.”

Related publication

Gymrek M, Willems T, Guilmatre A, Zeng H, Markus B, Georgiev S, Daly MJ, Price AL, Pritchard JK, Sharp AJ, Erlich Y. Abundant contribution of short tandem repeats to gene expression variation in humans. Nat Genet. 2015 Dec 7.