The most complete view of the human genome yet sets new standard for use in precision medicine
New research decodes the most elusive, difficult-to-sequence regions of the genome from populations around the world, rewriting knowledge of human biology and setting a new benchmark for precision medicine
Jackson Laboratory
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Discover how hidden complexities of the human genome are revealed by scientists from The Jackson Laboratory. Technological advancements are now allowing us to assemble continuous genomes with unprecedented clarity. This breakthrough also enables scientists to identify and resolve complex rearrangements within the genome. In this JAX in Motion, learn how this new level of discovery could revolutionize healthcare and our understanding of human health.
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Credit: The Jackson Laboratory
An international team of scientists has decoded some of the most stubborn, overlooked regions of the human genome using complete sequences from 65 individuals across diverse ancestries. The study, published online today in Nature and co-led by The Jackson Laboratory (JAX), reveals how hidden DNA variations that influence everything from digestion and immune response to muscle control—and could explain why certain diseases strike some populations harder than others.
This milestone builds on two foundational studies that reshaped the field of genomics. In 2022, researchers achieved the first-ever complete sequence of a single human genome, filling in major gaps left by the original Human Genome Project. In 2023, scientists released a draft pangenome constructed from 47 individuals—a critical step toward representing global genetic diversity. The new study significantly expands on both efforts, closing 92% of the remaining data gaps and mapping genomic variation across ancestries with a breadth and resolution never before achieved.
“For too long, our genetic references have excluded much of the world’s population,” said Christine Beck, a geneticist at JAX and the University of Connecticut Health Center who co-led the work. “This work captures essential variation that helps explain why disease risk isn’t the same for everyone. Our genomes are not static, and neither is our understanding of them.”
By decoding DNA segments once thought too complex or variable to analyze, the study sets a new gold standard for genome sequencing and propels the field toward a more complete and inclusive vision of human biology. The findings clear a critical path for advancing precision medicine and ensuring that future discoveries benefit all populations—not just those historically overrepresented in research.
Hiding within our DNA
Scientists decode DNA by reading the order of its building blocks, called nucleotides, which act like letters in an instruction manual to direct all body functions. Current technologies can read most of that text but often miss or misread long, complex, and highly repetitive segments that span millions of letters that influence how genes work. These long stretches are called structural variants, and they can increase disease risk, protect the body, or offer no apparent effect at all.
Structural variants mainly arise when cells replicate and repair DNA, especially in sections with extremely long and repetitive sequences prone to errors. Unlike many other types of genetic variation, there are different types of structural variants, and they can span large regions of DNA. These structural variants include deletions, duplications, insertions, inversions, and translocations of genome segments. More complex variations, where large DNA chunks rearrange and fuse in unpredictable ways, were a primary focus of the new study.
Complex rearrangements of genomes can also drive evolutionary changes that shape our biology, like how the human brain became larger and more sophisticated over time. But mapping these changes contiguously is remarkably difficult because they scramble the genome in ways that defy decoding — like trying to make sense of pages from a book that’s been torn up, rearranged, and reassembled without seeing the original version.
“It's only been in the last three years that finally technology got to the point where we can sequence complete genomes,” said Charles Lee, the Robert Alvine Family Endowed Chair and a JAX geneticist who in 2004 discovered the widespread presence of structural DNA variation in people’s genomes. “Now, we've captured probably 95% or more of all these structural variants in each genome sequenced and analyzed. Having done this for not five, not 10, not 20—but 65 genomes—is an incredible feat.”
Turning on the light
Until now, geneticists could only chart the “easiest” of structural variations in our DNA, leaving in the dark not only the most tangled, repetitive regions, but also their connection to rare genetic diseases. The new research has now broken that logjam, untangling 1,852 previously intractable complex structural variants and sharing an open-source playbook that any scientists sequencing genomes to this level can use in their laboratories.
Resolving these previously “hidden” regions across a wide range of ancestries turns areas that were once genetic blind spots into valuable sources of insight.
The work completely resolved the Y chromosome from 30 male genomes, shedding light on a chromosome that has been particularly challenging to resolve due to its highly repetitive sequences, and which JAX scientists fully sequenced from telomere to telomere just 18 months ago. In addition, the team fully resolved an intricate region of human genomes associated with the immune system called the Major Histocompatibility Complex, which is linked to cancer, autoimmune syndromes, and more than 100 other diseases.
The work also provides full sequences for the notoriously repetitive SMN1 and SMN2 region, the target of life-saving antisense therapies for spinal muscular atrophy, as well as a gene called NBPF8 involved in developmental and neurogenetic disease. The amylase gene cluster, which helps humans digest starchy foods according to a recent JAX study, was also fully sequenced.
The study additionally mapped transposable DNA elements in unprecedented detail, cataloguing 12,919 of these mobile element insertions across the 65 individuals. These elements, which can “jump” around the genome and change how genes work, accounted for almost 10% of all structural variants. In 1983, Barbara McClintock, a Hartford, Conn. native, received the Nobel Prize in Physiology and Medicine for her discovery of similar “jumping genes”, also known as transposable elements, in corn.
Some of these jumping genes in this study were even found in centromeres—regions of the chromosome that are essential for cell division and extremely difficult to sequence due to their repetitive DNA. Overall, the work accurately resolved and validated 1,246 human centromeres, shedding light on the extreme variability at their cores.
“With our health, anything that deals with susceptibility to diseases is a combination of what genes we have and the environment we’re interacting with,” Lee said. “If you don't have your complete genetic information, how are you going to get a complete picture of your health and your susceptibility to disease?”
The work was made possible by genome sequencing techniques that combine highly accurate medium-length DNA reads with longer, lower-accuracy ones. The interpretation of variation in the genomes was driven by software from JAX that accurately catalogues variants between two human sequences. This software has now pushed forward to identifying structural variation within the most complex regions of human DNA.
“Just because we have a long, complete sequence doesn’t mean we actually know what’s in it. It’s like having a really good book, but there are still some pages we can’t read, and these tools are finally allowing us to interpret those missing parts of the genome,” said Peter Audano, a JAX computational biologist in the Beck lab who developed and implemented the variant-finding software. “Now we can say, ‘Here’s a mutation, it starts here, ends there, and this is what it looks like.’ That’s a huge step forward. Now, scientists studying autism, rare diseases, and cancers will have the tools to see everything we've been missing for decades.”
This work was conducted in collaboration with more than 20 institutions, including the University of Washington, the European Molecular Biology Laboratory, Heinrich Heine University, University of Pennsylvania, Clemson University, Yale University and the University of Colorado under the auspices of the Human Genome Structural Variation Consortium.
About The Jackson Laboratory
The Jackson Laboratory (JAX) is an independent, nonprofit biomedical research institution with a National Cancer Institute-designated Cancer Center. JAX leverages a unique combination of research, education, and resources to achieve its bold mission: to discover precise genomic solutions for disease and empower the global biomedical community in the shared quest to improve human health. Established in Bar Harbor, Maine in 1929, JAX is a global organization with nearly 3,000 employees worldwide and campuses and facilities in Maine, Connecticut, California, Florida, and Japan. For more information, please visit www.jax.org.
Journal
Nature
Method of Research
Data/statistical analysis
Article Title
Complex genetic variation in nearly complete human genomes
Article Publication Date
23-Jul-2025
Complex genetic variation revealed in diverse human genomes
Near-complete genome sequences of 65 individuals from five continents and 28 population groups advance discovery of human DNA code alterations
University of Washington School of Medicine/UW Medicine
Genome assemblies from 65 individuals, representing a variety of the world’s populations, are advancing the scientific exploration of complex genetic structural variation.
Structural variations are genetic code alterations that span more than 50 base pairs, the rungs on the DNA ladder. These changes were hard to detect until the recent advent of newer sequencing technologies and analytical algorithms, as well as larger collections of more complete, diverse genomes.
Results from the latest work in this area, conducted by the Human Genome Structural Variation Consortium with participants from the international 1000 Genomes Project, are reported in the scientific journal Nature.
Evan E. Eichler, professor of genome sciences at the University of Washington School of Medicine in Seattle and a Howard Hughes Medical Institute investigator, is one of six joint senior authors on the paper. His recent postdoctoral scholar, Glennis A. Logsdon, now an assistant professor of genetics at the University of Pennsylvania’s Perelman School of Medicine, is the first lead author along with three other researchers.
“These complete genomes from diverse genetic backgrounds are providing us new insights into how genomes have changed over time.” Eichler said. “It’s like geneticists have just been presented with a brand new microscope to see the true complexity of human genetic variation for the first time”.
In addition to expanding the catalog of structural variations, the Human Genome Structural Variation Consortium also obtained new insights into centromere differences among people. A centromere – appearing as a constricted area on a chromosome – is a control center for separating genetic materials before cell division. Genome areas involved in centromere form and function are some of the most diverse, quickly evolving genetic regions in humans.
“The level of diversity within human centromeres is just remarkable,” said Logsdon. “We see differences in their sequence, structure, and organization that suggest these regions are evolving more quickly than we ever thought before. This rapid evolution may be important for how centromeres function and adapt over time.”
Although complex structural variations have been difficult to spot and analyze, they are important finds because they are much more likely to alter the expression of genes. After identifying such variation between and within populations, it is now easier to determine if the differences result in disease or other traits, like helping our ancestors adapt to their environments.
Structural variations in our genomic code can occur in several ways: deletions, inversions, duplications, transpositions, mobile element insertions, or more intricate rearrangements. Scientists study these variations to see whether they significantly affect gene function or gene expression.
Genome sequencing by the Consortium closed 92% of all the gaps in previous assemblies—most of which corresponded to these complex variants. In analyzing this set of diverse human genomes, the international collaboration of scientists uncovered up to 26,115 structural variants per individual for a total of more than175,000 sequence-resolved events that were seen at least once.
A few other highlights from the research include:
Improved assemblies of several Y chromosomes. Y chromosomes are difficult to assemble because they contain many highly repetitive sequences. With their several new Y chromosome assemblies, the researchers investigated one of the most extensive densely packed regions of the human genome, known as Yq12. Tight packing limits gene activity by making the DNA code less reachable by the mechanisms that copy the information contained in genes. While acknowledging that the Yq12 region remains challenging to probe, the researchers have begun making inroads in determining variation. Their findings suggest that it is among some of the most variable portions of a human’s Y chromosome.
New look at the major histocompatibility complex. This complicated region, highly relevant to disease research, is associated with immune function and autoimmunity dysfunction. Among the several locations in this complex examined for variations was an area important to vaccine response and to autoimmune diseases. Other studies of this complex region looked at variations in areas responsible for coding cell surface receptors that sense and signal the presence of invaders like viruses.
Centromere variations. Genome regions associated with centromeres are among the most highly prone to mutations. The lengths of more than a fifth of centromeres vary by more than 1.5-fold, and about a third vary in structure. Not surprisingly, the researchers found a large number of new variants – more than 4,000 based on their complete sequence of 1,246 centromeres. The researchers also noticed indications suggesting that sometimes two sites, rather than one, exist for the kinetochore – a structure for the attachment and control of the microscopic ropes that pull apart chromosomes during cell division. The researchers pointed out that additional research would need to confirm the functional consequence of these di-kinetochores.
Survival motor neuron genes (SMN1/SMN2). These genes are in a structurally complex region of biomedical interest. Mutations in or lack of the SMN1 gene are linked to spinal muscular atrophy (caused by the lack of a protein needed for muscle movement). SMN2 is a less powerful backup gene but a target of one of the most successful gene therapies. These genes are embedded in a region of long, repeated DNA sequences. This has made full sequencing nearly impossible until now. Through their assemblies of this region, researchers obtained the structure and copy number of these and a few other genes among several of the individuals in their study. They distinguished functional copies of SMN1 and SMN2. Their analysis also suggested potential disease-risk sites in a few of the genomes analyzed.
Senior scientists and institutions heading the “Complex genetic variations in nearly complete human genomes” project, in addition to Eichler at the UW, include Miriam Konkel at Clemson University in South Carolina, Jan Korbel at EMBL (the European Molecular Biology Laboratory) in Germany, Tobias Marschall at Heinrich Heine University in Germany, and Charles Lee and Christine R. Beck at the Jackson Laboratory for Genomic Medicine in Connecticut. Peter Ebert of the Marschall Lab at Heine University, and Peter A. Audano and Mark Loftus, both at the Jackson Laboratory for Genomic Medicine, along with Logsdon, were joint first authors.
Funding was provided by National Institutes of Health (NIH) grants U24HG007497, R00GM147352, R01HG002385 and R01HG010169, R01HG011649, K99HG012798, U01HG013748; NIH National Institute of General Medical Sciences R35GM133600, 1P20GM139769, 1R35GM138212; NIH National Institute of Allergy and Infectious Disease (NIAID) U01AI090905; NIH National Cancer Institute (NCI) R01CA261934, R21CA259309, P30CA034196; National Science Foundation (NSF) Career 2046753, the Ministry of Culture and Science of North Rhine-Westphalia (PROFILNRW-2020–107-A), and the German Research Foundation (DFG) 496874193. This work was also supported, in part, by the Intramural Research Program of the National Human Genome Research Institute, the Jürgen Manchot Foundation, Howard Hughes Medical Institute, and the Düsseldorf School of Oncology (SPATIAL).
The researchers also thank the individuals who provided their samples for sequencing and analysis to the 1,000 Genomes Project.
Journal
Nature
Method of Research
Experimental study
Subject of Research
Human tissue samples
Article Title
Complex genetic variation in nearly complete human genomes
Article Publication Date
23-Jul-2025
COI Statement
Evan E. Eichler. is a scientific advisory board member of Variant Bio, Inc. C. Lee is a scientific advisory board member of Nabsys. Sergey Koren has received travel funds to speak at events hosted by Oxford Nanopore Technologies. The following authors have previously disclosed a patent application (No. EP19169090) relevant to Strand-seq: Jan O. Korbel, Tobias Marschall, and David Porubsky. The other authors declare no competing interests.
Beyond 1000 genomes: Going deeper and wider
Ten years after the end of the 1000 Genomes Project, brand new insights emerge from its sample set, providing a more complete view of human genetic variation than ever before
image:
New analysis of the 1000 Genomes sample set yields brand new insights, providing a more complete view of human genetic variation than ever before.
view moreCredit: Daniela Velasco/EMBL
Completed in 2003, the Human Genome Project gave us the first sequence of the human genome, albeit based on DNA from a small handful of people. Building upon its success, the 1000 Genomes Project was conceived in 2007. The project began with the ambitious aim of sequencing 1,000 human genomes and exceeded it, publishing results gleaned from over 2,500 individuals of varying ancestries in 2015. Together, these projects have contributed to much of our knowledge about the genetics that make us unique and underlie our biology.
Now, 10 years down the road, EMBL scientists and their collaborators have revealed exciting new insights into human biology through deeper analysis of samples from this vast resource, using methods and technologies not available a decade ago. The resulting datasets, shared in two back-to-back publications in the journal Nature, constitute what may be the most complete overview of the human genome to date.
“About 15 years ago, most human genome sequencing relied on 'reads’ from small stretches of DNA – not enough to piece together a full genome, but sufficient to allow studies of genetic variation in larger parts of the genome,” said Jan Korbel, Group Leader and Interim Head at EMBL Heidelberg, and co-senior author of the new studies. "However, since about five years ago, it has become possible to routinely sequence human genomes with new commercially available technologies that can decode much longer stretches of DNA, allowing us to assemble the full genome of individuals and assess all parts of the genome for genetic variation.”
These technologies are collectively known as long-read sequencing methods, and EMBL scientists have used them to improve our understanding of cancer development and for environmental research. "We wanted to take advantage of the power of these new transformative sequencing techniques to learn more about human genetic variation,” said Korbel.
Genetic variations – differences in DNA sequence between individuals – help make each of us unique and play an important role in health and disease. While such variations can take the form of small differences, e.g. in one or a few 'letters’ of the genetic code, they can also be much more profound, with entire long stretches of DNA being deleted, inverted, repeated, or added in certain individuals.
It is now known that such ‘structural’ variations are not only common but also play a major role in many genetic diseases, including cancer. 'Maps’ of such variation across the human genome are also highly relevant clinically, as they serve as a reference to understand what goes wrong under disease conditions.
The two new studies use long-read sequencing technologies to dive deeper into such structural variations across the genome. For both studies, the Korbel Group teamed up with the lab of Tobias Marschall at Heinrich Heine University Düsseldorf, Germany, which is composed of experts in genome data science.
Enhancing the human pangenome
The first study looks at 1,019 genomes from the 1000 Genomes Project dataset, spread across 26 populations from five continents. Using long-read sequencing methods and teaming up with Siegfried Schloissnig from the Institute of Molecular Pathology (IMP) Vienna, Austria, the researchers created detailed maps of structural variations across the genomes of these individuals. In addition to generating new biological knowledge, with this new information, they could expand by more than twentyfold the 44-genome reference graph published by the Human Pangenome Reference Project in 2023.
For this study, the researchers also collaborated with Ewan Birney's team and Sarah Hunt at EMBL-EBI, as well as Bernardo Rodríguez Martín from the Centre for Genomic Regulation (CRG), Spain, among others.
“The original 1000 Genomes Project created a map of genome locations that are variable in the human population, and this enabled us to systematically search for regions associated with common diseases,” said Hunt. “That first map was built from short variants, but we already know of cases where longer variants are associated with disease. The new map from this study is more precise and deeper than other structural variant maps created so far and will enable us to seek new disease links.”
The second study uses a much smaller sample set of only 65 individuals but combined several powerful sequencing methods to put together genomes that are more complete than any ever sequenced before. For several chromosomes, the researchers assembled end-to-end sequences, a remarkable feat considering that human chromosomes can be hundreds of millions of base pairs (i.e. 'letters') long. This study was carried out in collaboration with researchers from several leading US institutes, who together formed part of the Human Genome Structural Variation Consortium.
“The Human Genome Structural Variation Consortium brings together people who are experts in different techniques and genomic areas and shows the power of international collaboration to drive discovery,” said Hunt. “This work reveals new biological insights by shining a light on parts of the genome we could not previously see and has created a toolkit for the analysis of further genomes.”
Korbel believes the studies strongly complement each other. "One study uses less sequencing power, but a much larger cohort. The other uses a smaller cohort, but much more sequencing power per sample. This led to complementary conclusions,” he said.
Such complete datasets have tremendous clinical relevance, since they serve as references against which genetic variations in disease can be identified and checked. In an additional experiment, the researchers showed that using the larger dataset of 1,019 genomes as a reference significantly improved the accuracy of identifying disease-associated variants compared to previous methods.
The datasets also yielded interesting new biological insights. For example, the study with 1,019 samples helped elucidate a new mechanism by which transposons – sometimes called ‘jumping genes’ – can help move stretches of DNA to new locations within the genome, giving rise to new variants. The 65-genome dataset, on the other hand, helped scientists understand certain sections of the genome that are very difficult to study using traditional methods, such as centromeres. Centromeres are the spots where two strands of the chromosome attach to each other when cells divide (forming the well-known X-shape), and disruptions in them have been linked to many disorders, including immune disorders and cancer.
“These two studies underscore the crucial role of repetitive DNA in shaping the human genome, uncovering a reservoir of genetic variation within regions that were largely missed in previous reference datasets due to their repetitive and complex nature,” said Bernardo Rodríguez-Martín, former member of the Korbel group, now Group Leader at the CRG and co-senior author of one of the studies.
A new resource for genome biologists
The new datasets have been made publicly available to researchers worldwide to analyse and use. The studies also forced innovation in the form of new genomic analysis methods, which the scientists created to analyse data at a scale much greater than previous studies had attempted.
"Through these studies, we have created a comprehensive and medically-relevant resource that can now be used by researchers everywhere to better understand the origins of human genomic variation, and see how it is affected by a plethora of different factors,” said Tobias Marschall, Professor at Heinrich Heine University Düsseldorf and co-senior author on the two studies. "This is a great example of collaborative research opening up new vistas in genomic science and a step towards a more complete human pangenome.”
Journal
Nature
Article Title
Complex genetic variation in nearly complete human genomes
Article Publication Date
23-Jul-2025
Human genome ‘re-read’ greatly expands catalogue of large genetic variation
Resequencing 1,019 genomes from 26 populations across five continents reveals a treasure trove of genetic variation hidden in repetitive regions of DNA
image:
Bernardo Rodríguez-Martin (left) and Emiliano Sotelo-Fonseca pictured at the Centre for Genomic Regulation (CRG) in Barcelona
view moreCredit: Omar Jamshed/Centro de Regulación Genómica
Researchers have significantly expanded the catalogue of known human genetic variation. The resulting datasets, shared in two back-to-back publications in the journal Nature, constitute what may be the most complete overview of the human genome to date.
The first paper, jointly led by the European Molecular Biology Laboratory (EMBL), Heinrich Heine University Düsseldorf (HHU) and the Centre for Genomic Regulation (CRG) in Barcelona, analysed the genomes of 1,019 people drawn from 26 populations on five continents.
The researchers specifically looked for structural variants in the human genome. These are large chunks of DNA that have been deleted, duplicated, inserted, inverted or shuffled. Differences in structural variants between individuals can mean changes to thousands of DNA letters at once, often knocking out genes and driving many rare diseases and cancers.
The team found and categorised more than 167,000 structural variants across the 1,019 individuals, doubling the known amount of structural variation in the human pangenome, a reference that stitches together DNA from many people instead of relying on a single genome. Each person carried a median of 7.5 million letters’ worth of structural changes, underscoring how much genome editing nature performs on its own.
“We found a treasure trove of hidden genetic variation in these populations, many of which were underrepresented in earlier reference sets. For example, 50.9% of insertions and 14.5% of deletions we found have not been reported in previous variation catalogues. It’s an important step to map blind spots in the human genome and reduce the bias that has long favoured genomes of European descent and paves the way for therapies and tests that work just as well for people everywhere,” says Dr. Bernardo Rodríguez-Martín, co-corresponding author of the study.
Around three in five (59%) of the variants uncovered occurred in fewer than one per cent of individuals, a level of rarity crucial for diagnosing genetic disease because it can help filter out harmless variations more effectively. In tests, the new reference set reduces the list of suspect mutations from tens of thousands to just a few hundred, accelerating the path to the diagnosis of rare genetic syndromes and other types of diseases like cancer.
Bernardo Rodríguez-Martín began working on the project in Jan Korbel’s lab at EMBL and completed it after moving to the CRG when starting his own group. He developed SVAN, a software which categorises every DNA change, like “extra piece copied” or “chunk deleted”, helping the team sift through the genetic data to discern new patterns.
SVAN revealed that more than half of the newly mapped diversity in the human genome was found to lie in highly repetitive stretches of DNA, parts of the genome once dismissed as junk or too hard to study. “Repetitive elements represent a rich and previously overlooked reservoir of genetic diversity. They are key protagonists in human diversity, disease and evolution,” says Emiliano Sotelo-Fonseca, PhD student at the CRG and co-author of the first study.
These repetitive segments of DNA include mobile elements, also known as ‘jumping genes’ due to their ability to copy and paste themselves around the genome. The researchers found that among the thousands of mobile elements in the human genome, most of the germline mutagenesis derives from the activity of a few dozens of highly active elements.
For example, one particularly hyperactive LINE-1 element was found to hijack a powerful regulatory switch to make far more copies of itself than usual, scattering extra genetic material across many people’s DNA. The researchers saw a similar trick with another class of jumping genes called SVAs.
“Our work shows how mobile elements boost their activity by hijacking our genome regulation buttons, an underappreciated strategy that could help drive diseases like cancer and which merits further research,” says Dr. Rodríguez-Martín.
The second paper, jointly led by the European Molecular Biology Laboratory (EMBL) and Heinrich Heine University Düsseldorf (HHU), used a much smaller sample set of only 65 individuals but combined several powerful sequencing methods to piece together human genomes in unprecedented detail.
The approach helped researchers decode the hardest-to-read stretches, including centromeres. The near-complete, gap-free assemblies of every chromosome for these individuals helped researchers detect large genetic variants within those regions missed by the first paper and other studies.
The findings show that combining the approach of paper one, with many genomes sequenced at modest depth, with the approach of paper two, with a few genomes in high detail, is the fastest path to a complete, inclusive map of human genetic diversity.
"One study uses less sequencing power, but a much larger cohort. The other uses a smaller cohort, but much more sequencing power per sample. This led to complementary conclusions,” says Dr. Jan Korbel, Group Leader and Interim Head at EMBL Heidelberg, and co-senior author of both studies.
Both papers re-sequenced individuals from the 1000 Genomes project, the landmark effort that mapped global genetic diversity in 2015. The project relied on “short read” sequencing technology, which could only read very small bits of DNA at a time. These were too short to reveal big chunks of DNA that are missing or copied, long stretches that flip direction or repeats that look almost identical in many places.
The advances made by the new studies were possible thanks to “long-read” sequencing, a recent technology that reads thousands to tens-of-thousands of DNA letters in one go, helping researchers find large amounts of hidden variation undetectable with previous methods.
The two papers also make important inroads towards the construction of a human pangenome reference. For the last twenty years, scientists have used one person’s DNA sequence as the “standard” human genome. A pangenome would be better suited for personalised medicine, reflecting global diversity.
By developing innovative algorithms that can analyse 1,019 diverse genomes for breadth and 65 ultra-complete genomes for depth, the researchers provide a roadmap that makes assembling a true human pangenome more practical rather than aspirational, particularly as long-read sequencing costs are falling.
"Through these studies, we have created a comprehensive and medically-relevant resource that can now be used by researchers everywhere to better understand the origins of human genomic variation, and see how it is affected by a plethora of different factors,” says Tobias Marschall, Professor at Heinrich Heine University Düsseldorf and co-senior author of both studies. "This is a great example of collaborative research opening up new vistas in genomic science and a step towards a more complete human pangenome.”
Journal
Nature
Method of Research
Experimental study
Subject of Research
Not applicable
Article Title
'Structural variation in 1,019 diverse humans based on long-read sequencing
Article Publication Date
23-Jul-2025
