Nat commun: scientists find important clues to predict disease! Genotype prediction is not as easy as you think!

March 9, 2018 / BIOON / - the more information you have, the more likely you are to predict what will happen next Clinicians and health researchers are also often looking for genetic mutations to predict the risk of birth defects in the fetus, or the risk of a person suffering from a certain disease, but these predictions are often inaccurate Researchers from the University of Calgary have now found an important factor that has changed our understanding of the relationship between gene mutations (genotypes) and their performance (phenotypes) in humans, which may help us improve the accuracy of prediction in the future Picture source: Cumming medical school "the purpose of this work is to help us understand why we also carry a gene mutation, some people are sick and some people are healthy." Rebecca green, a postdoctoral researcher at Benedikt Hallgrimson lab, the study's lead author, said "This is very common in cleft lip and palate Two children with the same gene mutation may have cleft lip and palate in one child and not in the other." In order to further explore the reasons, the researchers studied the gene expression level It has long been thought that changes in gene expression will lead to changes in the characteristics of these genes Many changes in features (such as face shape, height or blood pressure) are determined by differences in gene expression levels Using mouse embryos, they created a series of mutations that gradually reduced the level of expression of a gene called Fgf8, which is essential for normal facial development They gradually reduced the expression level of the gene from 100% to 20% Then they recorded the relationship between the level of gene expression and the degree of facial changes, and found that the relationship was neither proportional nor constant, but nonlinear "Our results show that even if the gene expression level is reduced by 50%, your face is completely normal But further reduction doesn't mean more defects - you can have many results: from a completely typical face to almost no face " Hallgrimson, director of the Department of cell biology and anatomy at Cumming School of medicine, said "These effects lead to nonlinear changes between genotype and phenotype If you don't know the relationship, you can't predict phenotypes based on genotype " The results were published in nature communications "This is a key point in predicting disease from genotype." Said Dr hallgrimsson "It improves our understanding of how genes interact with everyone, and it tells us how different results can be produced." Hallgrimson speculated that if researchers were to explore most of the really important genes, they might find similar results "The science of predicting phenotypes from genotypes is not as advanced as people think." Said Dr hallgrimsson "The prediction tools we are using need to take nonlinearity into account to modify and improve the algorithms for predicting phenotypes using genomic information This optimization is essential to predict disease risk " This work is also of great significance to evolutionary biology All organisms carry the same number of mutations In order to survive, a species must be able to tolerate certain gene mutations and successfully develop and reproduce This study shows that the non-linearity in development is the main reason for this phenomenon Reference: Rebecca M Green et al Developmental nonlinearity drives phenomenal robust, nature communications (2017) Doi: 10.1038/s41467-017-02037-7