“We're going to map genomic diversity and make science more equitable,” said a human genome leader

Karen Miga presents herself as the “satellite biologist” and has her justification. She is a researcher and professor at the University of California in Santa Cruz, United States, and studies the “satellite DNA” of cells. It's about the repeated DNA that forms a satellite band. Although it seems a distant issue for everyday life, with her effort and dedication to that subject, Dr. Miga made another scientific feat possible worldwide: they described the first sequencing of the entire human genome. It had the collaboration of 100 researchers.

The achievement included regions of the DNA of the human species never seen before that are related to diseases such as muscular dystrophy and some cancers, among others, and to brain development. It will involve more information so that progress can be made in the development of increasingly personalized diagnostic and treatment methods for patients.

In the 1990s, different groups of researchers had decoded the genome of a bacterium, a yeast, and a worm. Between 2000 and 2003, American scientists Francis Collins, from the public sector, and Craig Venter, from a private company, both drafts and final works on the deciphering of the human genome with different methodologies were announced with fanfare. Researchers from the United Kingdom, France, Japan, Germany and China also collaborated in these. More than $3 billion was allocated to read every letter of a person's DNA.

But in reality, those who focused on the human species only got an accurate “picture” of 92% of the genome in 2003. The remaining 8% was too complex for the technology of the time to be able to decode, and that percentage remained outstanding. On that “slope”, Karen Miga and her collaborators worked.

“I began my scientific career as a student in the laboratory of scientist Evan Eichle r during the launch of the first human genome project in 2001,” he told Infobae. That researcher, he added, “had the vision and made his effort to complete the human genome of reference, and that shaped my vision of genomics many years before the Telomere to Telomere Consortium was formed.” The Consortium started operating in 2019.

Miga acknowledged: “I found my love for satellite DNAs, tandem repeats in the persistent gaps of our genome, with Hunt Willard as a tutor. Finally, I did my postdoctoral training with David Haussler and Jim Kent, recognized for joining the first human genome through public effort and for their passion to share these resources broadly and openly. In general, I have had a unique vision of the human genome project, of the past, of the present and of the future. It's an honor to be a small part of that legacy.”

The human genome is made up of just over six billion individual letters of DNA, spread over 23 pairs of chromosomes. Eighty percent of the pending genome contained highly repeated sequences and largely discarded them as “junk” DNA. Among the repeated regions were the parts that hold the two strands of the chromosomes together and which play a crucial role in cell division. There were also “pieces” that give instructions for the cell's protein factories, and others that include genes that can help species adapt. And it was not known what the correct order of all those repeated pieces was.

There was another problem getting to the whole genome. Most cells contain two genomes, one from the father and the other from the mother. When trying to assemble all the pieces, the sequences of each parent can be mixed, and the actual variation within each individual genome was hidden.

Dr. Eichler, who is part of the Howard Hughes Medical Institute, had the idea of obtaining a complete genome by sequencing only one of the genomes instead of solving two at the same time. For this he used a set of cell lines, which was being studied by the geneticist at the University of Pittsburgh, Urvashi Surti: due to a failure in normal development, these cells have two copies of the father's DNA and none of the mother's. That cell line is what made possible — to a large extent — the new assembly of the genome.

Other changes also contributed to the breakthrough. During these two decades, there was innovation in the development of gene sequencing equipment manufactured by Oxford Nanopore Technologies and Pacific Biosciences. With Adam Phillippy, Dr. Miga promoted the creation of the Telomere to Telomere consortium in 2019, seeing that technology was already in place that allowed one million letters of DNA to be accurately read at a time to understand the most difficult parts of the genome.

In addition to the set of cell lines, the new equipment and the collaborative work of more than 100 researchers, this time the complete sequencing of the genome also had the imprint of a woman as a leader. Did you notice the difference? , Infobae asked Dr. Miga. He only replied, “I am very happy to represent our consortium, along with the other Telomeres by Telomeres leaders, Adam Phillippy and Evan Eichler. We have published six papers with the whole genome. About half of the authors are women and we are celebrating the achievements of a large number of early-stage scientists.”

There will hardly be any more talk about “junk DNA” after the 6 papers published by the consortium in the journal Science. “'Junk DNA' is just one way of describing DNA whose function we don't quite understand. We are hopeful that this comprehensive map will help researchers find new meaning and function in these previously ignored regions,” Miga said. The possibility of finding more answers for different diseases is now open.

“The possibility of studying each base of entire genomes (or telomeres by telomeres) will lead to new genetic discoveries that will ultimately improve our understanding of human health and disease,” she said. “The new regions provide maps that could be useful in understanding common structural chromosomal abnormalities seen in the general population, such as robertsonian translocations affecting the short arms of acrocentric chromosomes, which have just been published for the first time as part of our study,” commented.

In addition, he added, “we expect to have maps of all centromeric regions, or places that are important for our chromosomes to separate correctly every time a cell divides, could help us understand aneuploidies, such as trisomy 21 or Down syndrome, or other common errors in chromosome copy numbers in cancers and early development”.

Meanwhile, Dr. Miga is not satisfied with the entire human genome. “We are going to generate maps with global genomic diversity to make science more equitable.” The fact is that the genome decoded in 2003 was based only on the samples taken from only 11 individuals. Together with Dr. Eichler, they launched the Human Pangenome Project. It is funded by the United States National Institute for Human Genome Research (NHGRI) in Bethesda, Maryland, with $30 million. They are looking for a detailed sequencing of the genome, including 350 people from different ethnic backgrounds.

“The idea is to generate more complete maps of human genomes around the world. This will increase genomic diversity to make science more equitable. Our goal is to generate the maps rather than decipher the results,” he said. All data will be shared and genomic medicine is intended to be more equitable with all humanity. “To account for the full diversity of human genetic variation, the Human Pangenome Consortium has joined the Telomere by Telomere Consortium to build a collection of high-quality genomes from diverse populations. It will be a fundamental objective in the coming years,” said Miga. “It's important that we get it right, and our team focuses on quality to ensure that this resource has a broad benefit,” he said.

The Pangenome is being done in a different way than previous projects. Within the team, there are experts in bioethics who monitor each step to ensure that high standards of research ethics are met. In addition, all 350 genomes will come from cell lines that contain copies of both parents. This will mean that they have to use complex computer tools to separate genomes and ensure that they capture structural variation accurately. They have already completed 70 genomes within that initiative. The goal is to finish 350 by 2024.

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