Scientists have been trying to find the final parts of the human genome for nearly 20 years, approaching its decipherment, but have failed. So far.
WASHINGTON – Scientists say they have finally put together a complete genetic plan for human life by adding the missing pieces to a puzzle nearly completed two decades ago.
The international team described the first-ever sequence of the complete human genome – a set of instructions for creating and maintaining a human – in a study published Thursday in the journal Science. The previous attempt, noted around the world, was incomplete because modern DNA sequencing technology could not read some of its parts. Even after the updates, he lacked about 8% of the genome.
“Some of the genes that make us unique humans were actually in this ‘dark genome matter’, and they were completely missed,” said Evan Eichler, a researcher at the University of Washington who was involved in current efforts and the original human genome project. “It took more than 20 years, but we finally did it.”
Many – including Eichler’s own students – thought it was over. “I taught them, and they said, ‘Wait.’ Isn’t this the sixth time you’ve declared victory? I said, “No, this time we really, really did it!”
Scientists have said that this complete picture of the genome will give humanity a deeper understanding of our evolution and biology, and open the door to medical discoveries in areas such as aging, neurodegenerative diseases, cancer and heart disease.
“We’re just expanding our capabilities to understand human disease,” said Karen Miga, author of one of six studies published Thursday.
The study concludes decades of work. The first human genome project was announced at a ceremony at the White House in 2000 by leaders of two competing organizations: an international state-funded project led by the U.S. National Institutes of Health and a private Celera Genomics company in Maryland.
The human genome consists of about 3.1 billion DNA subunits, pairs of chemical bases known by the letters A, C, G and T. Genes are chains of these letter pairs that contain instructions for creating proteins, the building blocks of life. Humans have about 30,000 genes organized into 23 groups called chromosomes that are located in the nucleus of each cell.
Previously, our map had “large and permanent gaps, and these gaps fall on quite important regions,” Miga said.
Miga, a genomics researcher at the University of California, Santa Cruz, worked with Adam Filippi of the National Institute of Human Genome Research to organize a team of scientists to start a new genome from scratch in order to sequence it all, including previously missing pieces. A group named after sites at the very ends of chromosomes called telomeres is known as the telomere-in-telomere consortium, or T2T.
Their work adds new genetic information to the human genome, corrects previous errors and detects long stretches of DNA that are known to play an important role in both evolution and disease. A study version was published last year before being reviewed by scientific colleagues.
“I would say it’s a major improvement on the Human Genome Project, which doubles its impact,” said geneticist Ting Wang of Washington University School of Medicine in St. Louis, who was not involved in the study.
Eichler said some scientists had previously believed that unknown areas contained “garbage”. Not him. “Some of us have always believed that there is gold on these hills,” he said. Eichler is paid by the Howard Hughes Medical Institute, which also supports the Associated Press. Department of Health and Science.
It turns out gold includes many important genes, he said, such as those that are integral to making the human brain bigger than a chimpanzee, with more neurons and connections.
To find such genes, scientists needed new ways to read the mysterious genetic language of life.
To read genes, you need to cut DNA strands into pieces hundreds to thousands of letters long. Sequencing machines read the letters in each piece, and scientists try to arrange the pieces in the correct order. This is especially difficult in areas where letters are repeated.
Scientists said some areas were illegible before machines for gene sequencing were improved that now allow them, for example, to accurately read a million letters of DNA simultaneously. This allows scientists to see genes with repetitive regions in the form of longer strings rather than fragments that they later had to put together.
The researchers also had to overcome another problem: most cells contain the genomes of both mother and father, which confuses attempts to properly assemble the details. T2T researchers bypassed this by using a cell line from a single “complete hydatidiforme mole,” an abnormally fertilized egg that contains no fetal tissue that has two copies of the father’s DNA and neither of the mother’s.
The next step? Mapping more genomes, including those that include the gene collections of both parents. This effort did not reflect one of the 23 chromosomes found in men called the Y chromosome because the mole contained only X.
Wang said he was working with the T2T team on a reference consortium for human pangenoma, trying to create “reference” or template genomes for 350 people representing the breadth of human diversity.
“Now we’ve got one genome right, and we have a lot more to do,” Eichler said. “It’s the beginning of something really fantastic for human genetics.”
