MADRID.– All people were at some point a single almighty cell of 0.1 millimeters, the result of the union of an egg from their mother and a sperm from their father. Inside that solitary cell there was already an exclusive and amazing text: the genome, more than 3000 million chemical letters with the instructions to multiply and become a human being with 30 trillion cells. is what he American geneticist Francis Collins, a fervent Christian and former director of the Human Genome Project, calls “the language of God.” But there is another god above that supposed god. Virtually all of a person’s cells share the same original operating manual, although some read a few pages, and become neurons in the brain, and others read other passages, and give rise to cells of the muscle, heart, or any other organ. . An international consortium today presents the most complete map of that other god who chooses how to read the book of life: the epigenome.
The scientists dove into the genetic material of four deceased organ donorstwo women and two men, as detailed Roderic Guigó, researcher at the Center for Genomic Regulation (CRG) in Barcelona and co-author of the paper. “This is the most complete personal map of the human epigenome,” says Guigó. The breakthrough opens a new door to medicine. The epigenome are chemical compounds that bind to the genome –the famous DNA– as if they were highlighters and bookmarks that indicate the parts of the book that must be read. The process is fundamental in the normal development of a fertilized egg, but also in the appearance of diseases, such as cancer.
Another international consortium already published a reference map of the epigenome in 2015, but Guigó points out that it was built on the human reference genome, an “archetypal” text that does not correspond to any individual in particular, but rather is a mixture of scraps DNA from a dozen people. The new study, published in the specialized magazine Cell, shows the personalized maps of 30 different tissues –lung, heart, liver– of the four deceased people. “We can investigate for the first time the epigenomic variation both through fabrics and individuals”, celebrates Guigó.
He ADN of a cell is organized into 23 pairs of packages, called chromosomes. In each pair, a chromosome is inherited from the mother and another from the father. The Italian biotechnologist Beatrice Borsari stresses that it is the first time that both the genome and the epigenome of the two copies of each chromosome have been studied with this level of detail. “If DNA is a book, the epigenome is the person who reads that book.a kind of librarian who decides which parts are read”, illustrates Borsari, who did his doctoral thesis at the CRG and is now doing research at Yale University (USA), another of the consortium institutions.
A person’s genome, compared to the reference published two decades ago, contains about 4.5 million mutations. Most are harmless, but some can be harmful or even beneficial to health. The new epigenomic maps illuminate the effect of these mutations, further detailing whether they were inherited from the mother or the father. “We have been able to analyze the mutations in the genome of specific individuals, how they modify their epigenome and, therefore, how they can change the way in which these instructions are read in various tissues”, explains Borsari. In the world of DNA, errors in the book also cause the transformation of the librarian who reads it.
American geneticist Thomas Gingerasone of the leaders of the consortium, believes that this is a definitive step towards personalized medicine. “It has been very clear, for a long time, that the ideal would be to obtain the sequence of the genome of the whole world and analyze the effect of the variations, as a basis to diagnose and choose a treatment. Medicine is directed to that destination. And this is an attempt to provide a paradigm for doing so,” Gingeras, of the Cold Spring Harbor Laboratory, said in a statement.
The authors produced a catalog of millions of mutations, named EN-TEX, with which they trained an algorithm that predicts the impact of these changes on the risk of suffering from diseases. Borsari cites the example of primary ciliary dyskinesia, a rare respiratory disorder that affects the lungs and hearing. “It is a problematic disease and we have been able to study some mutations that occur in a gene and understand how they change the epigenome. If I have a patient with these mutations, I can make predictions,” says the biotechnologist.
Borsari stresses another advantage of his map: the ability to investigate the effects of mutations on organs that are difficult to access in a living person, such as the heart or brain. The authors used machine learning techniques to be able to detect patterns and draw conclusions from a simple blood test.
the geneticist Manel Esteller applauds the new work, in which he did not participate. “They are the foundations on which to build specific research that tells us about the risk of cancer, susceptibility to serious infection or factors related to healthy aging,” says Esteller, director of the Josep Carreras Leukemia Research Institute. , in Badalona (Barcelona).
The authors acknowledge the limitations of their study.: They only investigated the epigenome of four people, and all of them had European ancestry and lived in the United States. “We would like to add more individuals, to have greater statistical power, and incorporate people of different ethnicities. A mutation can be common in white individuals, but rare in other groups”, explains Borsari.
The Italian scientist is already working on the next phase of medicine, in her laboratory at Yale University. “Knowing the mutations in the genome is very important, but knowing how they change the epigenome is another level that takes us much further. If the DNA is my book and the epigenome is the person reading the book, the next step is to find out what happens after you’ve read the book. How does the cell change?” she wonders.
By Manuel Ansede
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