Why decoding the entire human genome is a breakthrough for curing diseases

A team of scientists have assembled the entire genetic plane of human life by adding the missing pieces to a puzzle that was almost started more than two decades ago.

In a research published in the journal Science, the group of international researchers described the first sequencing of the entire human genome, that is, the set of instructions for build and maintain a human being. 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, about 8% of the genome was missing.

Scientists said that this comprehensive picture of the genome will give humanity a greater understanding of our evolution and biology, while also opening the door to medical discoveries in areas such as aging, neurodegenerative diseases, cancer and heart disease.

California-based companies Pacific Biosciences (PACBio) and UK-based Oxford Nanopore used different technologies together to decipher that missing 8% genetic. PacBio used a system called HiFi, where base pairs circulate, literally like circles, until they are read in full and in high fidelity, hence the name. The system dates back a few years of use and represents a big step forward in “reading” both in length and accuracy of the longest sequences.

Meanwhile, Oxford Nanopore uses electric current in its proprietary devices. The base pair strands are pressed through a microscopic nanopore, only one molecule at a time, where a current hits them to observe what kind of molecule they are. By removing each molecule, scientists can identify the entire strand.

The human genome consists of about 3.1 billion subunits of DNA, chemical base pairs known by the letters A, C, G and T. 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 into 23 groups called chromosomes that are found in the nucleus of each cell.

Humans have 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 extensive experience 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.

A two-decade investigation

This research concludes decades of work. The first draft of the human genome was announced at a ceremony held at the White House in 2000 by the heads of two competing entities: A publicly funded international project led by an agency of the National Institutes of Health of the United States, and a private company, Celera Genomics, based in Maryland.

“This 8% of the genome has not been overlooked because of its lack of importance, but because of technological limitations,” the researchers wrote. “High-precision long-read sequencing has finally eliminated this technological barrier, allowing comprehensive studies of genomic variation across the human genome. Such studies will necessarily require a complete and accurate human reference genome, which will ultimately drive adoption of the T2T-CHM13 package presented here,” Dotto added.

Scientists from the Telomere-to-Telomere Consortium (T2T) completed the first truly complete 3,055 billion base pair (bp) sequence of a human genome, representing the greatest improvement of the human reference genome since its initial launch.

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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