The human genome contains many common features and characteristics beyond just being made of four bases. There are protein coding genes, and regions that help control the expression of those genes, for example. And there are many areas where the DNA sequence become repetitive. These repetitious regions can be highly variable from one person to another, and while most of it was once written off as junk, we know now that there are also many important parts of this so-called repeatome.
Short tandem repeats are a major feature of non-coding DNA. They are motifs that can range from one to six bases in length, and there are about 1.5 million of them in the human genome. Advances in genetic techniques have allowed scientists to learn more about them, and variations in repeat lengths have been linked to a variety of traits, and many have now been associated with human diseases.
Earlier this year, a tool called TR-gnomAD was created to help researchers explore the significance of tandem repeat (TR) expansions. The work was reported in Cell.
Two recent studies have also highlighted the significance of repeat expansion disorders (REDs). There are about fifty disorders that have been linked to tandem repeats.
Repeat expansions are thought to be the most common cause of inherited neurological disorders, including inherited forms of amyotrophic lateral sclerosis (ALS), fragile X syndrome, and frontotemporal dementia.
While they are now estimated to occur in about 1 in 3,000 people, a new study reported in Nature Medicine has suggested that REDs may be far more common. After analyzing the genomes of about 80,000 individuals, the researchers determined that the frequency of REDs in their cohort was 1 in 283 people, and based on other statistical factors, they suggested that the frequency of REDs in the general population may be two to three more times more common than what is now estimated.
An unrelated study reported in Nature Genetics has revealed that repeat expansions also have a more significant effect on human development and cognition than we knew. Repeat expansions may cause at least 0.3 percent of all intellectual disabilities, the study determined. This research also only focused on a small number of repeat expansions in the human genome. Since there are many more of them, there could be also many more causes of intellectual or developmental disability waiting to be discovered in the repeatome.
"Our research brings to light how these previously underappreciated genetic features can have a profound impact on human intelligence," said corresponding study author Andrew Sharp, PhD, Professor of Genetics and Genomic Sciences at Icahn Mount Sinai.
Sources: Queen Mary University of London, The Mount Sinai Hospital, Nature Genetics, Nature Medicine
