Deciphering the entire human genome will help to find “the lost genetic cause” of diseases

Expectations for having completely unraveled the human genome are growing and multiplying. A team of scientists managed to assemble as a complex puzzle the entire genetic plane of human life, adding the missing pieces to a research began more than two decades ago.

In a research published in the journal Science, a group of international researchers described the first sequencing of the entire human genome, that is, the set of instructions for building and maintaining a human being.

“The first human genome was released in 2000. In 2013 we had the latest version. But there was an 8% missing that remained completely unknown and hidden. It's a milestone that took us 20 years to achieve. It is the starting point for understanding more about human biology and how these new parts of the genome could affect human development and health,” explained Chilean bioinformatics Cristina Soto, who was part of the T2T Consortium, the international team that deciphered the genome and published its results last week. The 33-year-old researcher is currently pursuing her doctorate at the University of California in Davis, USA.

“This is the first step. We had a hard time getting here. Those 8% were structures that were difficult to find and rebuild. Now it opens a dark box that we didn't know it contained. We are now looking to know their biological implications and will help us understand diseases of genetic origin, the causes of which we often do not find and we call it a lost genetic cause,” Soto completed in an interview on Radio Mitre.

Previous work, held around the world, was incomplete because DNA sequencing technologies of the time were not able to read certain genomic regions. Even after the updates. The joint effort to describe this sequence has presented, for the first time, the natural 'instructions' of genetic inheritance in the human species thanks to six teams of scientists from the Telomere to Telomere Consortium (T2T) group.

Although the Human Genome Sequencing Consortium published its first drafts of the human genome in 2000, the limitations of DNA sequencing technologies did not allow a complete study to be achieved. At that time, only the chromatic fraction of the genome was covered, leaving unfinished important heterochromatic regions, which constituted 8 percent.

Now, thanks to a new sequencing technology (deoxyribonucleic acid), T2T has a complete sequence of 3055 million base pairs of a human genome, named T2T-CHM13. It includes spaceless assemblies for all chromosomes except Y-, an error correction in the previous references and introduces nearly 200 million sequence base pairs, containing 1956 gene predictions -99 of which are predicted to encode proteins.

Genes are strings of these pairs identified with letters that contain instructions for making proteins, the building blocks of life. Humans have about 30,000 genes, organized 46 chromosomes, in 23 pairs, representing tens of thousands of individual genes. Each gene consists of several base pairs composed of adenine (A), thymine (T), guanine (G), and cytosine (C). There are billions of base pairs in the human genome. But the genome that the researchers sequenced didn't come from a person, but from a hydatiform mole, a rare mass or growth that forms inside the uterus at the beginning of a pregnancy. This tissue forms when the sperm fertilizes an egg without a nucleus, so it contains only 23 chromosomes, such as a gamete (sperm or egg), instead of the 46 found in the DNA of a human cell. These cells simplify the computational effort but can be a limitation.

Scientists explained that their work increased the number of DNA bases from 2.92 billion to 3.05 billion, an increase of 4.5%, and that the count of genes encoding proteins increased by only 0.4%, to 19,969. According to experts, the work may also lead to other new knowledge, including those related to how genes are regulated.

Science is increasingly reaching knowledge about humanity with greater depth and accuracy. Having sequenced the entire human genome will help avoid various diseases. And also, understanding the mechanisms of origin of a given pathology will help to develop more direct and precise drugs against diseases so that they have a lower prevalence”, Dr. Jorge Dotto, a world reference as a geneticist, explained to Infobae, who has a long history in the United States and Europe.

He added: “This complete information will allow us to make better decisions about our body, since it changes the perception of the ignorance we had. For example, the decision of what foods we need to eat to strengthen our defenses. In our microbiome is 80% of our immune system. Knowing more about the microbiota and what probiotics, which are living bacteria, we need to incorporate will help us modulate and make more effective the functioning of our immune system, which could be more precise to reduce inflammation at the molecular level in our body in the face of a disease”.

Dotto also referred to improvements in the behavior of the skin and the female reproductive system. “We have to help people get less sick, and this work of total genetic sequencing is going to help us do that,” concluded the founding specialist of the “Genetics Center”, a company dedicated to precision medicine, nutrition and high sports performance.

“Some of the genes that make us unequivocally human were actually in this 'dark matter of the genome' and were completely missing,” said Evan Eichler, a researcher at the University of Washington who participated in this project and the original Human Genome Project. “It took more than 20 years, but we finally succeeded.” Many people — including Eichler's own students — thought that the project had already been completed. “I was teaching them and they said, 'Wait a minute. Isn't this like the sixth time you've sung victory? ' I said, 'No, this time we really did it! '” “We are expanding our opportunities to understand human disease,” said Karen Miga, author of one of six published studies.

The new genome is a leap forward, the researchers said, made possible by new DNA sequencing technologies developed by two private sector companies: California's Pacific Biosciences, also known as PACBio, and British Oxford Nanopore. Its technologies for reading DNA have very specific advantages over tools that have long been considered fundamental for researchers.

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