Scientists have reconstructed the complete genome of a real person, including full sets of chromosomes from each parent, an achievement expected to advance research, improve diagnosis of genetic diseases, and make personalized genomics a routine part of medical care. The work comes from the Telomere-to-Telomere (T2T) Consortium, led by researchers at Johns Hopkins University, the National Human Genome Research Institute, and the National Institute of Standards and Technology, and establishes the most complete and highest-quality human genome sequence built so far, filling gaps that previous approaches missed.
“It will soon become commonplace to sequence an individual’s entire genome,” said Adam Phillippy, senior author of the research published in Cell. “What will that enable? And what does the future of medicine look like when you can generate someone’s complete genome at birth, attach it to their medical record, and then use that to inform precision medicine throughout their life? Complete, personalized genomes are now possible for anyone.”
The findings, published as part of a 12-paper package in Cell and Cell Genomics, build on the T2T Consortium’s 2022 completion of the first full human genome, which filled in the last 8% of a single genome sequence. This time, the team reconstructed a “diploid” genome, containing two distinct chromosome copies, one from each parent. “The first T2T project was like assembling a huge jigsaw puzzle,” Phillippy said. “This time, we had pieces from two similar puzzles, one from mom and one from dad, all thrown into the same box. So, it’s a harder computational challenge, but we’ve figured it out.”
The team sequenced the HG002 genome, a widely used reference sample from a living donor, spanning each chromosome “telomere to telomere” and revealing 15% more of the genome than before, including regions tied to cancer and neurological disorders, plus more than 900 million previously missing DNA letters. Co-senior author Justin Zook said the work “gives technology developers the standard they need to measure and improve accuracy across the most complex regions of the human genome.”
Phillippy called it “a paradigm shift from trying to find the differences between your genome and a reference to actually reconstructing your complete, unique genome.” The Human Genome Project cost roughly $5 billion in today’s dollars; a more complete result can now be produced for about $5,000. Phillippy said this could close diagnostic gaps in rare genetic diseases, where doctors currently can’t identify a cause in over half of cases, and eventually improve risk prediction for cancers, heart disease, and neuropsychiatric conditions. Companion papers applying the same approach to species including macaque, zebra finch, and giraffe are also expected to inform research into evolution and biodiversity.
“It will soon become commonplace to sequence an individual’s entire genome,” said Adam Phillippy, senior author of the research published in Cell. “What will that enable? And what does the future of medicine look like when you can generate someone’s complete genome at birth, attach it to their medical record, and then use that to inform precision medicine throughout their life? Complete, personalized genomes are now possible for anyone.”
The findings, published as part of a 12-paper package in Cell and Cell Genomics, build on the T2T Consortium’s 2022 completion of the first full human genome, which filled in the last 8% of a single genome sequence. This time, the team reconstructed a “diploid” genome, containing two distinct chromosome copies, one from each parent. “The first T2T project was like assembling a huge jigsaw puzzle,” Phillippy said. “This time, we had pieces from two similar puzzles, one from mom and one from dad, all thrown into the same box. So, it’s a harder computational challenge, but we’ve figured it out.”
The team sequenced the HG002 genome, a widely used reference sample from a living donor, spanning each chromosome “telomere to telomere” and revealing 15% more of the genome than before, including regions tied to cancer and neurological disorders, plus more than 900 million previously missing DNA letters. Co-senior author Justin Zook said the work “gives technology developers the standard they need to measure and improve accuracy across the most complex regions of the human genome.”
Phillippy called it “a paradigm shift from trying to find the differences between your genome and a reference to actually reconstructing your complete, unique genome.” The Human Genome Project cost roughly $5 billion in today’s dollars; a more complete result can now be produced for about $5,000. Phillippy said this could close diagnostic gaps in rare genetic diseases, where doctors currently can’t identify a cause in over half of cases, and eventually improve risk prediction for cancers, heart disease, and neuropsychiatric conditions. Companion papers applying the same approach to species including macaque, zebra finch, and giraffe are also expected to inform research into evolution and biodiversity.