Nature: Mutations in series repeat sequences in the genome or play a key role in the development of autism spectrum disorder

JANUARY 18, 2021 // -- In a recent study published in the international journal Nature, scientists from the University of California and other institutions found that mutations in specific DNA regions called tandem repeats or play a key role in the development of autism spectrum disorder (ASD) may also be directly related to autism risk.
researcher Melissa Gymrek says few researchers study these repetitive sequences because they are generally non-coded, i.e. they don't make proteins and their function is unclear, and it's difficult to analyze them.
our study found that repeated sequences in series may affect gene expression, as well as the collective risk of specific diseases, such as ASD.
Photo Source: In the NHGRI article, researchers studied about 1,600 families, including mothers, fathers and a normal esopaedic child, as well as a child with ASD; specifically, they looked for new mutations in offspring, not parents; and researchers found an average of 50 concatenated new mutations in each child's body, regardless of whether they were affected by autism.
On average, children with ASD carry more mutations in their bodies, and although their growth is statistically significant, it is relatively modest; however, using a new algorithmic tool, researchers found in children with ASD that the mutation rate of series repeat sequences was higher and that these mutations were considered to be the most evolutionaryly harmful. 'In our initial analysis, the ratio of children with ASD to normal neurologic child body mutations was 1.03, just close to 1, but when the tools mentioned above were used, we found that the relative risk increased by about 2.5 times, and children with autism carried more severe mutations than the control group,' the
researchers said.
it is significant to find so many previously undiscovered series of repeat sequences because they match the number of point mutations commonly found in each child (i.e., a single change in the A, T, C, and G that make up DNA).
This study also provides valuable information about many of the factors that influence these new mutations, such as the fact that older fathers' offspring carry more mutations in this series of repeat sequences;
, however, there are often more changes in the length of repetitions from the mother's body, but researchers don't know the mechanism behind it.
mutations from the father tend to increase or decrease by one copy, but mutations from the mother tend to increase or decrease by two or more copies, so researchers observe more obvious events when the mutations come from the mother.
researchers note that we have identified a range of genes already associated with ASD, as well as a number of candidate genes that need to be determined in more in-depth studies in the laboratory.
'We're excited that we're going to go into more detail later to clarify the specific mechanisms of action of these new ASD genes, because repetition tends to change more than point mutations, and we can learn a lot of very valuable information from one location in the genome,' said Gymrek, a researcher at the end of the day.
() Original source: Mitra, I., Huang, B., Mousavi, N. et al. Patterns of de novo tandem repeat mutations and their role in autism. Nature 589, 246–250 (2021). doi：10.1038/s41586-020-03078-7