2020-09-13 14:24:25
More than a decade ago, an international group of researchers began a project known as Genotype-Tissue Expression. The objective was to study, analyzing genetics, how diverse human beings are.
We know that each one of us is made up of tens of trillions of cells, cells that come from a single cell, formed from the fusion of our mother’s egg with our father’s sperm. The mixture obtained contained half of the chromosomes of each parent, 23 of each. In this creative game, parents give different sets of chromosomes to their children, making siblings genetically different from each other. Even in the case that two twin brothers arise from a single fertilized egg, with the same initial genetic information, since the ADN copy is copied over and over again to generate all the cells of the different tissues and organs, copying errors occur that introduce genetic differences.
Thus, analyzing the genome, any pair of people chosen at random among the 7.8 billion that now inhabit planet Earth will be different, genetically speaking. However, the most normal thing is that these differences are not important and that, in general, the people who have them are healthy.
There are genetic differences between individuals that are evident. Women, for example, have two X chromosomes, while men have one X and one Y. But there are many other differences that distinguish any two people and that can be located on any chromosome, without ceasing to be people. healthy.
Another fundamental difference, not only between people but between the cells of our own body, depends on the activity of genes. Each human cell contains around 20,000 genes and not all of them are active, on the contrary, it is the selective activity of the genes that allows the cells of the different organs to be different and carry out specific activities. Thus, a cell from one part of the heart is different from another from one part of the kidney, not because they have different genetic information, but because different genes are activated or expressed in them.
The knowledge of the differences in gene activity in the cells of “healthy” people is what the project pursues GTEx. The seven papers that have just been published in Science and Science Advances reveal the results of as many investigations.
Among these publications, the research carried out by Meritxell Olivaour guest today on Talking to Scientists, who, along with Manuel Muñoz-Aguirre, Sarah Kim-Hellmuth, and a broad group of researchers, has discovered that the activity or expression of more than a third of each person’s genes is connected to sex in at least one tissue.
It was already known that many human phenotypes, including diseases, show up differently depending on the sex of the person. However, it is unknown to what extent there is a relationship between sex and the expression of genes in a healthy person. To find these connections, Meritxell Oliva and her team have studied the sexual and gene expression differences in 44 human tissues provided by the project GTEx, analyzing 16,245 sequencing samples of ARN and genotypes of 838 adult individuals.
The results of the study reveal that the effects of gender on gene expression are much more abundant than previously thought. A total of 37% of all genes exhibit sex-biased expression in at least one tissue. The tissue samples studied present variations in gene expression between men and women in aspects as important as the distribution of body fat, in the metabolism of drugs, in the inflammatory response or cancer.
The team has produced a catalog of sex differences in gene expression and in the genetic regulation of gene expression. This catalog provides a fundamental basis for future research that affects the study of diseases and the differential effect that they can have between men and women.
The fact that these differences in gene expression in tissues according to sex are known has serious implications when it comes to understanding how different people behave in the face of diseases and what treatments should be applied. Thus, the symptoms or consequences of a disease can be different in men and women because their genes are activated with different intensity. These changes influence the strength or weakness of the disease and the differences in drug metabolism indicate that the optimal doses needed may be different depending on whether the patient is male or female. This has important implications for the companies that develop these drugs because they would be forced to change their validation protocols in trials with volunteers.
Four other studies of GTEx are published in Science. Francois Aguet and his colleagues discuss the effects of gene regulation on human tissues. Nicole Ferraro and others identify rare functional genetic variations. Kathryn Demanelis and colleagues are studying predictors of telomere length. And Sarah Kim-Hellmuth and her group report on cell-specific gene regulation in human tissues.
In a Science Advances study using data from 360,000 individuals from the UK Biobank, Aine Duffy investigated how tissue-specific differences could be used to inform drug side effects that often explain clinical trial failure. In a second study, Milton Pividori and his team applied a method to help identify potential associations between genes and traits, their analysis helping to inform which complex genetic traits may be therapeutic targets.
Use these lines to inform about the project GTEx and show some of the main points of our conversation with Meritxell Oliva. I invite you to listen to it.
Meritxell Oliva is a Research Fellow at the University of Chicago in the Department of Medicine’s Section of Genetic Medicine, at the Institute for Genomics and Systems Biology, and in the Department of Public Health Sciences.
References:
Meritxell Oliva, Manuel Muñoz-Aguirre, Sarah Kim-Hellmuth et al. The impact of sex on gene expression across human tissues 11 SEPTEMBER 2020 • VOL 369 ISSUE 6509
F. Aguet at The GTEx Consortium The GTEx Consortium atlas of genetic regulatory effects across human tissues
S. Kim-Hellmuth et al. Cell type–specific genetic regulation of gene expression across human tissues,
K. Demanelis et al. Determinants of telomere length across human tissues
NM Ferraro et al. Transcriptomic signatures across human tissues identify functional rare genetic variation
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