PNAS: Scientists have revealed the difference between pathogenic gene mutations and benign gene mutations

3, 2020 // -- In a recent study published in the international journal Proceedings of the National Academy of Sciences, scientists from the Cleveland Clinic and other institutions conducted a large-scale character analysis of 1,330 disease-related gene variants.
, the researchers identified features associated with pathogenic and benign mutations that may reveal the effects of mutations at the molecular level.
researcher Professor Dennis Lal said the study could provide a powerful resource for the transformation of individual genomics research into individualized diagnosis and precision medicine research, as well as help explain the causes of mutations and guide experimental research to help accelerate the development of individualized drugs.
Recent large-scale DNA sequencing studies have been able to detect millions of misaligned mutations, errors in DNA codes, or change the amino acid sequences that make up proteins, some of which are pathogenic, meaning that they alter the structure and function of proteins in a disease-inducing way, while other benign mutations have no effect on the health of the body, but most mutations are unclear because researchers don't know what their effects are.
Photo Source: CC0 Public Domain Although there are currently methods to predict the pathogenicity of mutants, these methods may not shed light on why some mutations are easier or less prone to disease than others, and their functional effects, in addition to pathogenic and benign mutations in almost all disease-related genes.
therefore, a better understanding of the mechanism differences between benign and pathogenic mutations may hopefully help develop new therapies for genetic diseases. The function of
protein is closely related to its three-dimensional structure, and in this study, the researchers identified and compared the protein properties of amino acids affected by pathogenic and benign error mutations, which are frequently mutated in pathogenic mutations compared to benign mutations (3-D mutation hot spots), which are important for protein adaptability and can also help explain pathogenic molecular determinants.
By searching and analyzing 1,330 disease-related genes, the researchers analyzed a set of 40 traits and found that 18 of them were significantly associated with pathogenic mutations, 14 were significantly associated with benign mutations, and the remaining eight were not significantly associated with any mutation type.
by analyzing genetic mutations in the context of a protein's three-dimensional architecture, researchers have for the first time proposed a molecular map of pathogenic mutations that could help shed light on the differences between benign and pathogenic mutations, said Lal, a researcher at the University of California, San Vegas.
study, researchers focused on 1,330 genes associated with rare types of genetic diseases, which may help them find more pathogenic genes and more mild genetic disorders.
researchers will continue to delve deeper into the causes and mechanisms that cause differences between benign and pathogenic mutations.
original source: Sumaiya Iqbal, Eduardo Pérez-Palma, Jakob B. Jespersen, et al. Comprehensive characterization of amino acid positions in protein structures reveals molecular effect of missense variants, Proceedings of the National Academy of Sciences (2020). DOI:10.1073/pnas.2002660117