Native functions of short tandem repeats

Abstract

Over a third of the human genome is comprised of repetitive sequences, including more than a million short tandem repeats (STRs). While studies of the pathologic consequences of repeat expansions that cause syndromic human diseases are extensive, the potential native functions of STRs are often ignored. Here, we summarize a growing body of research into the normal biological functions for repetitive elements across the genome, with a particular focus on the roles of STRs in regulating gene expression. We propose reconceptualizing the pathogenic consequences of repeat expansions as aberrancies in normal gene regulation. From this altered viewpoint, we predict that future work will reveal broader roles for STRs in neuronal function and as risk alleles for more common human neurological diseases.

Analytical Validation of Loss of Heterozygosity and Mutation Detection in Pancreatic Fine-Needle Aspirates by Capillary Electrophoresis and Sanger Sequencing

“…The difference can be one repeat or up to twenty-five repeats, creating a moving target the size of the STRs for detection [ 45 ]. In addition, expansion alterations add a further complication in STR detection [ 46 ]. Multiple methodologies are available for nucleic acid-based detection and measurement.…”

A comprehensive tandem repeat catalog of the human genome

“…Over 2 million TRs have been reported to occur in the human genome 17 , 18 , residing within both coding and non-coding regions and playing a crucial role in regulating gene expression, genome stability, and chromatin structure 19 – 21 . Yet, TR expansions have long been disregarded as a possible explanation of unexplained genetic disorders that are not neurological, largely due to the challenges in profiling them in high-throughput genomic sequencing datasets and in interpreting their clinical relevance 22 .…”

Regulation potential of transcribed simple repeated sequences in developing neurons

“…The biological functions of shorter tandem repeats are less well understood. Depending on the length of their repeated units, this group is often classified into microsatellites (≤9-bp units), minisatellites (10-60-bp units), and satellites (>60-bp units)(Wright and Todd 2023). These boundaries may differ depending on the study and the organism, and alternative terms such as short tandem repeats and simple sequence repeats are often used as synonyms for microsatellites.…”

“…The biological functions of shorter tandem repeats are less well understood. Depending on the length of their repeated units, this group is often classified into microsatellites (≤9-bp units), minisatellites (10-60-bp units), and satellites (>60-bp units) (Wright and Todd 2023).…”