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Researchers from the CAS disclose genome-wide variations in the secondary structure of DNA among people
[ 2021-05-18 ]

The genome of each individual varies. A common type of variation, termed Single nucleotide variation (SNV), represents a difference in a single nucleotide in the genomes of peoples. As the most studied genetic variations, SNPs are associated with some important traits of an individual, such as susceptibility to disease, drug response, medical outcome, and other health-related phenotypes.

Previously, research on SNP has mostly focused on the consequence of the change in an individual nucleotide in a one-dimensional context. Their biological consequences including, for example, induction of change in amino acid in a protein if the SNV falls into a protein-coding region. A recent study led by Dr. Zheng Tan from the Institute of Zoology, Chinese Academy of Sciences reveals that SNPs in the human genome interact with DNA motifs that can form four-stranded secondary structures called G-quadruplexes. As a result, such interactions result in millions of potential changes in secondary structures in the DNA of the human genome. In particular, most of these changes occur within genes and are enriched near transcription start sites, implying they affect gene regulation. Their work confirmed that such structural changes caused by a change in a single nucleotide could lead to a significant alteration in the expression of the host gene. The work appeared May 18, 2021, in the Proceedings of the National Academy of Sciences of the United States of America (https://www.pnas.org/content/118/21/e2013230118).

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Illustration. Potential G-quadruplex structure changes that can be induced by an SNV.

Genomic DNA provides a blueprint for all metabolic activities of a cell. The new findings made on the genome-wide structural variation in the human genomes provide an important addition to the mechanisms of how an SNV would influence the function of DNA. They will help us understand genetic variation and physiological consequences from a structural perspective. The structural variations should also represent a unique class of drug targets for individualized medicine, health assessment, and drug development.

 

 

(Contact:Zheng Tan, z.tan@ioz.ac.cn)

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