Researchers say they have finally put together the complete genetic plan for human life, adding the missing pieces to a puzzle that was almost completed two decades ago.
An international team described the first ever sequencing of a complete human genome – the set of instructions for building and maintaining a human – in research published Thursday in the journal Science. The previous effort, which was celebrated around the world, was incomplete because today’s DNA sequencing technologies could not read certain parts of it. Even after updates, it was missing about 8% of the genome.
“Some of the genes that make us unique human were actually present in this ‘dark matter in the genome’ and they were completely missing,” said Evan Eichler, a researcher at the University of Washington who participated in the current work and the original Human Genome Project. more than 20 years, but we got it in the end. “
Many – including Eichler’s own students – thought it was already done. “I taught them and they said, ‘Wait a minute. Is not this the sixth time you are proclaiming victory? I said,’ No, this time we did it really, really!
Researchers said that this complete picture of the genome will give humanity a greater understanding of our evolution and biology while opening the door to medical discoveries in areas such as aging, neurodegenerative conditions, cancer and heart disease.
“We are only broadening our opportunities to understand human diseases,” said Karen Miga, author of one of the six studies published on Thursday.
The research ends decades of work. The first draft of the human genome was announced at a White House ceremony in 2000 by leaders of two competing entities: an internationally publicly funded project led by a US National Institutes of Health agency and a private company, Maryland-based Celera Genomics.
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 strands of these letter pairs 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.
Before now, there were “large and persistent gaps that have been on our map, and these gaps fall into quite important regions,” said Miga.
Miga, a genomics researcher at the University of California-Santa Cruz, worked with Adam Phillippy of the National Human Genome Research Institute to organize the team of researchers to start from scratch with a new genome in order to sequence everything, including previously missing pieces. The group, named after the sections at the ends of the chromosomes, called telomeres, is known as the Telomere-to-Telomere, or T2T, consortium.
Their work adds new genetic information to the human genome, corrects past errors, and reveals long stretches of DNA that are known to play important roles in both evolution and disease. A version of the research was published last year before it was reviewed by scientific colleagues.
“This is a major improvement, I would say, of the Human Genome Project,” which doubles its impact, “said geneticist Ting Wang of the Washington University School of Medicine in St. Louis. Louis, who was not involved in the research.
Eichler said some researchers used to believe that unknown areas contained “garbage”. Not him. “Some of us always thought there was gold in those hills,” he said. Eichler is paid for by the Howard Hughes Medical Institute, which also supports the Associated Press’ Department of Health and Science.
It turns out that gold contains many important genes, he said, such as those that are integrated into making a person’s brain bigger than a chimpanzee’s, with more neurons and connections.
To find such genes, researchers needed new ways to read the cryptic genetic language of life.
Reading genes requires cutting the DNA strands into pieces that are hundreds to thousands of letters long. Sequencing machines read the letters in each piece and researchers try to place the pieces in the correct order. This is especially difficult in areas where letters are repeated.
Researchers said that some areas were unreadable before improvements in gene sequencing machines that now allow them to accurately read one million letters of DNA at a time, for example. This makes it possible for researchers to see genes with repeated regions that have longer strings instead of extracts that the latter had to put together.
Researchers also had to overcome another challenge: Most cells contain genome from both mother and father, confusing attempts to put the pieces together correctly. T2T researchers came around this by using a cell line from a “complete hydatidiform mole”, an abnormally fertilized egg that does not contain any fetal tissue that has two copies of the father’s DNA and none of the mother’s.
Next step? Mapping of several genomes, including those that include collections of genes from both parents. This experiment did not map one of the 23 chromosomes found in men, called the Y chromosome, because the mole contained only one X.
Wang said he works with the T2T group at the Human Pangenome Reference Consortium, which seeks to generate “references” or templates, through for 350 people representing the breadth of human diversity.
“Now we’ve got one through right and we have to do many, many more,” Eichler said. “This is the beginning of something really amazing in the field of human genetics.”
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