(ORDO NEWS) — Scientists have filled in millions of missing pieces of human DNA, creating the most complete, gap-free sequence of the human genome except for one tiny chromosome.
This feat, made possible by ever-improving genome sequencing technologies and a consortium of more than 100 scientists, sets a new benchmark for understanding human genetic diversity in all its glory.
In the process, the team also corrected thousands of structural errors in our previous most complete reference genome. This achievement cannot be underestimated: It holds great potential for a better understanding of human evolution and disease.
“Truly completing the sequencing of the human genome is like putting on a new pair of glasses,” says bioinformatician Adam Phillippi of the US National Human Genome Research Institute.
“Now that we can see everything clearly, we are one step closer to understanding what it all means.”
Since the launch of the Human Genome Project more than 30 years ago, genetic sequencing and data processing technologies have become faster, cheaper and more accurate, allowing researchers to select, sequence and compare more genomes every year.
But huge chunks of DNA – making up about 8 percent of the human genome – were still missing from the latest reference sequence scientists are using as a template to assemble new sequenced DNA samples.
Now scientists have pieced together those parts of the human genome that have long been considered “unsequencing” to assemble the most complete reference genome to date, and share their results in a collection of six articles published in the journal Science.
As a result of this painstaking research work, about 200 million base pairs of genetic information have been added to the human genome – a whole chromosome. Most of them are found in telomeres, the protective caps at the end of each chromosome, and in the dense middle regions of chromosomes called centromeres.
“Finally, tip to tip, telomere to telomere, we have a genome assembly that we can look at,” says Winston Thimp, a biomedical engineer at Johns Hopkins University.
It is wild to think that there were so many gaps in the human genome as we know it; millions of missing reasons, really. But it speaks to the mesmerizing beauty and complexity of the DNA that cradles within our cells and encodes every intimate detail of life.
“We’ve gained tremendous insight into human biology and disease by having about 90 percent of the human genome,” says bioinformatician David Haussler of the University of California’s (UC) Santa Cruz Genomics Institute.
“But there were a lot of important aspects that lay hidden, out of the view of science, because we didn’t have the technology to read those parts of the genome.”
Scientists first mapped the human genome decades ago by piecing together and overlaying “short reads” of DNA that captured just a few hundred bases at a time. Then, long-span sequencing allowed them to understand the meaning of previously “unreadable” repetitive DNA fragments that had defied research for a long time.
“These parts of the human genome, which we haven’t been able to study for 20+ years, are important to our understanding of how the genome works, genetic diseases, human diversity and evolution,” says Santa Cruz University geneticist Karen Miga, who led the consortium. researchers.
The new “gapless” genome, now over 3 billion bases long, could also shed light on how pairs of chromosomes move apart and divide without a hitch, on the mechanics of the so-called jumping genes that hop around the genome, and perhaps the crucial role long stretches of duplicated DNA.
“By discovering these new regions of the genome, we think that there will be genetic variations that contribute to the development of many different traits and disease risk,” says evolutionary biologist Rajiv McCoy of Johns Hopkins University. But he adds that “there is also the aspect of ‘we don’t know what we don’t know’ yet.”
Instead of being a mosaic of sequences collected from many people, the new reference genome was created using a special type of cell line that has two identical copies of each chromosome (unlike most human cells, which carry two slightly different copies).
This means there is still a lot of work to be done to complete the reference genome (the Y chromosome still needs to be finalized), but the group is getting closer to finally sequencing all the nucleotides of human DNA.
While researchers have high hopes that the near-complete genome, dubbed T2T-CHM13, could pave the way for a broader representation of human diversity, overall the field is still struggling with how to address historical injustices in genomic science and lack of diversity in genetics. research, which threatens to exacerbate health inequalities.
However, teams of scientists have already used an almost complete reference sequence to identify more than 2 million previously unknown variants in the human genome, which will enrich our understanding of how individual genetic differences can contribute to the development of certain diseases.
Of course, time will tell if personalized medicine can truly live up to its promise of providing affordable and targeted therapies based on a person’s genetic makeup, but researchers are optimistic.
“In the future, when a person’s genome is sequenced, we will be able to identify all the variants of their DNA and use this information to better manage their health,” Phillippi says.
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