Introduction – Company Background

GuangXin Industrial Co., Ltd. is a specialized manufacturer dedicated to the development and production of high-quality insoles.

With a strong foundation in material science and footwear ergonomics, we serve as a trusted partner for global brands seeking reliable insole solutions that combine comfort, functionality, and design.

With years of experience in insole production and OEM/ODM services, GuangXin has successfully supported a wide range of clients across various industries—including sportswear, health & wellness, orthopedic care, and daily footwear.

From initial prototyping to mass production, we provide comprehensive support tailored to each client’s market and application needs.

At GuangXin, we are committed to quality, innovation, and sustainable development. Every insole we produce reflects our dedication to precision craftsmanship, forward-thinking design, and ESG-driven practices.

By integrating eco-friendly materials, clean production processes, and responsible sourcing, we help our partners meet both market demand and environmental goals.

Core Strengths in Insole Manufacturing

At GuangXin Industrial, our core strength lies in our deep expertise and versatility in insole and pillow manufacturing. We specialize in working with a wide range of materials, including PU (polyurethane), natural latex, and advanced graphene composites, to develop insoles and pillows that meet diverse performance, comfort, and health-support needs.

Whether it's cushioning, support, breathability, or antibacterial function, we tailor material selection to the exact requirements of each project-whether for foot wellness or ergonomic sleep products.

We provide end-to-end manufacturing capabilities under one roof—covering every stage from material sourcing and foaming, to precision molding, lamination, cutting, sewing, and strict quality control. This full-process control not only ensures product consistency and durability, but also allows for faster lead times and better customization flexibility.

With our flexible production capacity, we accommodate both small batch custom orders and high-volume mass production with equal efficiency. Whether you're a startup launching your first insole or pillow line, or a global brand scaling up to meet market demand, GuangXin is equipped to deliver reliable OEM/ODM solutions that grow with your business.

Customization & OEM/ODM Flexibility

GuangXin offers exceptional flexibility in customization and OEM/ODM services, empowering our partners to create insole products that truly align with their brand identity and target market. We develop insoles tailored to specific foot shapes, end-user needs, and regional market preferences, ensuring optimal fit and functionality.

Our team supports comprehensive branding solutions, including logo printing, custom packaging, and product integration support for marketing campaigns. Whether you're launching a new product line or upgrading an existing one, we help your vision come to life with attention to detail and consistent brand presentation.

With fast prototyping services and efficient lead times, GuangXin helps reduce your time-to-market and respond quickly to evolving trends or seasonal demands. From concept to final production, we offer agile support that keeps you ahead of the competition.

Quality Assurance & Certifications

Quality is at the heart of everything we do. GuangXin implements a rigorous quality control system at every stage of production—ensuring that each insole meets the highest standards of consistency, comfort, and durability.

We provide a variety of in-house and third-party testing options, including antibacterial performance, odor control, durability testing, and eco-safety verification, to meet the specific needs of our clients and markets.

Our products are fully compliant with international safety and environmental standards, such as REACH, RoHS, and other applicable export regulations. This ensures seamless entry into global markets while supporting your ESG and product safety commitments.

ESG-Oriented Sustainable Production

At GuangXin Industrial, we are committed to integrating ESG (Environmental, Social, and Governance) values into every step of our manufacturing process. We actively pursue eco-conscious practices by utilizing eco-friendly materials and adopting low-carbon production methods to reduce environmental impact.

To support circular economy goals, we offer recycled and upcycled material options, including innovative applications such as recycled glass and repurposed LCD panel glass. These materials are processed using advanced techniques to retain performance while reducing waste—contributing to a more sustainable supply chain.

We also work closely with our partners to support their ESG compliance and sustainability reporting needs, providing documentation, traceability, and material data upon request. Whether you're aiming to meet corporate sustainability targets or align with global green regulations, GuangXin is your trusted manufacturing ally in building a better, greener future.

Let’s Build Your Next Insole Success Together

Looking for a reliable insole manufacturing partner that understands customization, quality, and flexibility? GuangXin Industrial Co., Ltd. specializes in high-performance insole production, offering tailored solutions for brands across the globe. Whether you're launching a new insole collection or expanding your existing product line, we provide OEM/ODM services built around your unique design and performance goals.

From small-batch custom orders to full-scale mass production, our flexible insole manufacturing capabilities adapt to your business needs. With expertise in PU, latex, and graphene insole materials, we turn ideas into functional, comfortable, and market-ready insoles that deliver value.

Contact us today to discuss your next insole project. Let GuangXin help you create custom insoles that stand out, perform better, and reflect your brand’s commitment to comfort, quality, and sustainability.

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Insole ODM factory in Taiwan

Are you looking for a trusted and experienced manufacturing partner that can bring your comfort-focused product ideas to life? GuangXin Industrial Co., Ltd. is your ideal OEM/ODM supplier, specializing in insole production, pillow manufacturing, and advanced graphene product design.

With decades of experience in insole OEM/ODM, we provide full-service manufacturing—from PU and latex to cutting-edge graphene-infused insoles—customized to meet your performance, support, and breathability requirements. Our production process is vertically integrated, covering everything from material sourcing and foaming to molding, cutting, and strict quality control.Custom graphene foam processing Thailand

Beyond insoles, GuangXin also offers pillow OEM/ODM services with a focus on ergonomic comfort and functional innovation. Whether you need memory foam, latex, or smart material integration for neck and sleep support, we deliver tailor-made solutions that reflect your brand’s values.

We are especially proud to lead the way in ESG-driven insole development. Through the use of recycled materials—such as repurposed LCD glass—and low-carbon production processes, we help our partners meet sustainability goals without compromising product quality. Our ESG insole solutions are designed not only for comfort but also for compliance with global environmental standards.Smart pillow ODM manufacturing factory Taiwan

At GuangXin, we don’t just manufacture products—we create long-term value for your brand. Whether you're developing your first product line or scaling up globally, our flexible production capabilities and collaborative approach will help you go further, faster.China custom insole OEM supplier

📩 Contact us today to learn how our insole OEM, pillow ODM, and graphene product design services can elevate your product offering—while aligning with the sustainability expectations of modern consumers.Taiwan foot care insole ODM development factory

The Atacama Desert, one of Earth’s harshest environments, contains surface soil with DNA from both living cells and external sources. A novel technique enables researchers to distinguish between internal and external DNA, revealing the microbes thriving in this extreme habitat. This method could also be adapted to study microbial communities in similarly hostile environments, including those on other planets. A novel technique separates living (iDNA) and dead (eDNA) microbial DNA, enabling precise analysis of microbial life in the Atacama Desert. This method reveals active microbes and offers new insights into extreme ecosystems. The Atacama Desert, stretching along the Pacific Coast of Chile, is the driest place on Earth and, due to its extreme aridity, inhospitable to most forms of life. Yet, not everything succumbs to its harsh conditions—studies of the desert’s sandy soil have uncovered diverse microbial communities. Investigating the roles of microorganisms in such environments is challenging, however, as it is difficult to distinguish genetic material from living microbes from that of dead ones. A new separation technique can help researchers focus on the living part of the community. In a paper recently published in the journal Applied and Environmental Microbiology, an international team of researchers describes a new way to separate extracellular (eDNA) from intracellular (iDNA) genetic material. The method provides better insights into microbial life in low-biomass environments, which was previously not possible with conventional DNA extraction methods, said Dirk Wagner, Ph.D., a geomicrobiologist at the GFZ German Research Centre for Geosciences in Potsdam, who led the study. Research in the Atacama Desert The microbiologists used the novel approach on Atacama soil samples collected from the desert along a west-to-east swath from the ocean’s edge to the foothills of the Andes mountains. Their analyses revealed a variety of living and possibly active microbes in the most arid areas. A better understanding of eDNA and iDNA, Wagner said, can help researchers probe all microbial processes. “Microbes are the pioneers colonizing this kind of environment and preparing the ground for the next succession of life,” Wagner said. These processes, he said, aren’t limited to the desert. “This could also apply to new terrain that forms after earthquakes or landslides where you have more or less the same situation, a mineral or rock-based substrate.” Most commercially available tools for extracting DNA from soils leave a mixture of living, dormant and dead cells from microorganisms, Wagner said. “If you extract all the DNA, you have DNA from living organisms and also DNA that can represent organisms that just died or that died a long time ago.” Metagenomic sequencing of that DNA can reveal specific microbes and microbial processes. However, it requires sufficient good-quality DNA, Wagner added, “which is often the bottleneck in low-biomass environments.” Challenges of Conventional DNA Extraction To remedy that problem, he and his collaborators developed a process for filtering intact cells out of a mixture, leaving behind eDNA genetic fragments left from dead cells in the sediment. It involves multiple cycles of gentle rinsing, he said. In lab tests they found that after 4 repetitions, nearly all the DNA in a sample had been divided into the 2 groups. When they tested soil from the Atacama Desert, they found Actinobacteria and Proteobacteria in all samples in both eDNA and iDNA groups. That’s not surprising, Wagner said, because the living cells constantly replenish the store of iDNA as they die and degrade. “If a community is really active, then a constant turnover is taking place, and that means the 2 pools should be more similar to each other,” he said. In samples collected from depths of less than 5 centimeters, they found that Chloroflexota bacteria dominated in the iDNA group. In future work, Wagner said he plans to conduct metagenomic sequencing on the iDNA samples to better understand the microbes at work, and to apply the same approach to samples from other hostile environments. By studying iDNA, he said, “you can get deeper insights into the real active part of the community.” Reference: “Inside the Atacama Desert: uncovering the living microbiome of an extreme environment” by Alexander Bartholomäus, Steffi Genderjahn, Kai Mangelsdorf, Beate Schneider, Pedro Zamorano, Samuel P. Kounaves, Dirk Schulze-Makuch and Dirk Wagner, 14 November 2024, Applied and Environmental Microbiology. DOI: 10.1128/aem.01443-24

Dr. Eimear Kenny has significantly contributed to the creation of an inclusive human pangenome reference, led by the international Human Pangenome Reference Consortium. The reference currently includes genomes of 47 people, aiming to reach 350 by 2024. This endeavor seeks to represent human genetic diversity more accurately, aiding disease diagnosis and treatment, and minimizing health disparities. Dr. Eimear Kenny, a renowned professor of Medicine, Genetics, and Genomic Sciences at the Icahn School of Medicine at Mount Sinai, has made substantial contributions to the international Human Pangenome Reference Consortium, leading to the creation of a more inclusive human pangenome reference. Eimear Kenny, PhD, had just completed undergrad and was working in her first computational genomics job more than 20 years ago when scientists announced the first (nearly) complete sequencing of the human genome—what was considered at the time to be the fundamental blueprint for all humans. The Human Genome Project aimed to map the entire genome in an effort to accelerate the diagnosis and eventual treatment of common and rare diseases. Now, Dr. Kenny, a Professor of Medicine, and Genetics and Genomic Sciences, at the Icahn School of Medicine at Mount Sinai, can count herself as one of a handful of elite scientists worldwide whose vital contributions have led to the creation of the new human “pangenome” reference, a collection of genome sequences that captures significantly more human diversity. Details on these novel developments were described in several Nature papers published last month. The work was led by the international Human Pangenome Reference Consortium, a group funded by the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health. Dr. Kenny is a Principal Investigator and lead scientist of the consortium. The new pangenome reference is a collection of different genomes from which to compare an individual genome sequence. Like a map of the subway system, the pangenome graph has many possible routes for a sequence to take, represented by the different colors. Credit: National Human Genome Research Institute A genome is the set of DNA instructions that helps each living creature develop and function. Genome sequences differ slightly among individuals. In the case of humans, any two peoples’ genomes are, on average, more than 99 percent identical. The small differences contribute to each person’s uniqueness and can provide insights about their health, helping to diagnose disease, predict outcomes and guide medical treatments. “We have had a single human reference for the past 20 years, and this genome reference has been extraordinarily powerful. It is a resource that has driven the sequencing of the genomes of tens or hundreds of millions of humans on the planet,” says Dr. Kenny, Professor of Medicine, and Genetics and Genomics Sciences at the Icahn School of Medicine at Mount Sinai, who is a co-author of the work. “However, it is limited in that most of the reference sequence only represents one person on the planet, so when you have rarer sequences or only in certain people, they are not represented. Therefore, we needed to really think about how to update the human reference and make it much more representative of diverse humans all over the world, which is what we have now done.” Goals for the Pangenome Reference The new pangenome reference includes genome sequences of 47 people, and the researchers aim to increase that number to 350 by mid-2024. Because each person carries a paired set of chromosomes, the current reference includes 94 distinct genome sequences, with a goal of reaching 700 distinct genome sequences by the completion of the project. “Basic researchers and clinicians who use genomics need access to a reference sequence that reflects the remarkable diversity of the human population. This will help make the reference useful for all people, thereby helping to reduce the chances of propagating health disparities,” says Eric Green, MD, PhD, NHGRI director. “Creating and enhancing a human pangenome reference aligns with NHGRI’s goal of striving for global diversity in all aspects of genomics research, which is crucial to advance genomic knowledge and implement genomic medicine in an equitable way.” Dr. Kenny, who is also Founding Director of the Institute for Genomic Health at Icahn Mount Sinai, leads research at the interface of genomics, medicine, and computer science to accelerate the use of genomics information in routine clinical care to improve human health. She uses machine learning approaches and massive-scale databases of genomic information for discovery of novel genetic variants impacting disease risk. She also oversees large clinical trials in on implementing genomic medicine in diverse populations. That expertise has paid off. “Across many individuals, my role in this consortium was to contribute to this international scientific effort, and, in particular, help select the genomes that make up the new pangenome reference so that this resource would best benefit many people around the planet,” she says. Population Genetics and Community Engagement Dr. Kenny co-led a team using population genetics approaches, community engagement, and outreach to include genomes from diverse populations in the pangenome. This will help address issues of underrepresentation and bias in genomics research, and can improve the accuracy and generalizability of research findings across different populations. The Human Genome Project completed in 2003 covered about 92 percent of the total human genome sequence. Recent technological advances such as long-read DNA sequencing, which reads longer stretches of the DNA at a time, helped researchers fill in those gaps to create the first complete human genome sequence. The developments were reported in a set of six papers in the April 1, 2022, issue of Science, along with companion papers published in several other journals. These findings were incorporated into the current pangenome reference. “I’m delighted about the advancements in genomics technology that we have today. This new era of long-read sequencing, along with other capabilities, allows us to get much higher resolution of genomic sequences and, in particular, more accurately identify larger genomic variants called structural variants, which have been until now very difficult to detect with the short-read technology. This has enabled us to accelerate the rate at which we can find medically relevant variants and dramatically reduce sequencing costs,” says Dr. Kenny. Importantly, knowing these variants better, Dr. Kenny says, will help elucidate which genes are truly rare or whether they may just be more common in certain parts of the world. “The other significant aspect is that we are really trying to make a resource that is truly working toward global representativeness. We need to have a path toward recognizing that humans everywhere on the planet need resources available to them that best work for them,” says Dr. Kenny. For more on this breakthrough, see: Human Pangenome Reference: A Deeper Understanding of Worldwide Genomic Diversity A Crystal Clear Image of Human Genomic Diversity Release of the New Human Pangenome Reference “A draft human pangenome reference” by Wen-Wei Liao, Mobin Asri, Jana Ebler, Daniel Doerr, Marina Haukness, Glenn Hickey, Shuangjia Lu, Julian K. Lucas, Jean Monlong, Haley J. Abel, Silvia Buonaiuto, Xian H. Chang, Haoyu Cheng, Justin Chu, Vincenza Colonna, Jordan M. Eizenga, Xiaowen Feng, Christian Fischer, Robert S. Fulton, Shilpa Garg, Cristian Groza, Andrea Guarracino, William T. Harvey, Simon Heumos, Kerstin Howe, Miten Jain, Tsung-Yu Lu, Charles Markello, Fergal J. Martin, Matthew W. Mitchell, Katherine M. Munson, Moses Njagi Mwaniki, Adam M. Novak, Hugh E. Olsen, Trevor Pesout, David Porubsky, Pjotr Prins, Jonas A. Sibbesen, Jouni Sirén, Chad Tomlinson, Flavia Villani, Mitchell R. Vollger, Lucinda L. Antonacci-Fulton, Gunjan Baid, Carl A. Baker, Anastasiya Belyaeva, Konstantinos Billis, Andrew Carroll, Pi-Chuan Chang, Sarah Cody, Daniel E. Cook, Robert M. Cook-Deegan, Omar E. Cornejo, Mark Diekhans, Peter Ebert, Susan Fairley, Olivier Fedrigo, Adam L. Felsenfeld, Giulio Formenti, Adam Frankish, Yan Gao, Nanibaa’ A. Garrison, Carlos Garcia Giron, Richard E. Green, Leanne Haggerty, Kendra Hoekzema, Thibaut Hourlier, Hanlee P. Ji, Eimear E. Kenny, Barbara A. Koenig, Alexey Kolesnikov, Jan O. Korbel, Jennifer Kordosky, Sergey Koren, HoJoon Lee, Alexandra P. Lewis, Hugo Magalhães, Santiago Marco-Sola, Pierre Marijon, Ann McCartney, Jennifer McDaniel, Jacquelyn Mountcastle, Maria Nattestad, Sergey Nurk, Nathan D. Olson, Alice B. Popejoy, Daniela Puiu, Mikko Rautiainen, Allison A. Regier, Arang Rhie, Samuel Sacco, Ashley D. Sanders, Valerie A. Schneider, Baergen I. Schultz, Kishwar Shafin, Michael W. Smith, Heidi J. Sofia, Ahmad N. Abou Tayoun, Françoise Thibaud-Nissen, Francesca Floriana Tricomi, Justin Wagner, Brian Walenz, Jonathan M. D. Wood, Aleksey V. Zimin, Guillaume Bourque, Mark J. P. Chaisson, Paul Flicek, Adam M. Phillippy, Justin M. Zook, Evan E. Eichler, David Haussler, Ting Wang, Erich D. Jarvis, Karen H. Miga, Erik Garrison, Tobias Marschall, Ira M. Hall, Heng Li and Benedict Paten, 10 May 2023, Nature. DOI: 10.1038/s41586-023-05896-x “Increased mutation rate and gene conversion within human segmental duplications” by Mitchell R. Vollger, Philip C. Dishuck, William T. Harvey, William S. DeWitt, Xavi Guitart, Michael E. Goldberg, Allison N. Rozanski, Julian Lucas, Mobin Asri, Human Pangenome Reference Consortium, Katherine M. Munson, Alexandra P. Lewis, Kendra Hoekzema, Glennis A. Logsdon, David Porubsky, Benedict Paten, Kelley Harris, PingHsun Hsieh and Evan E. Eichler, 10 May 2023. Nature. DOI: 10.1038/s41586-023-05895-y “Recombination between heterologous human acrocentric chromosomes” by Andrea Guarracino, Silvia Buonaiuto, Leonardo Gomes de Lima, Tamara Potapova, Arang Rhie, Sergey Koren, Boris Rubinstein, Christian Fischer, Human Pangenome Reference Consortium, Jennifer L. Gerton, Adam M. Phillippy, Vincenza Colonna and Erik Garrison, 10 May 2023, Nature. DOI: 10.1038/s41586-023-05976-y “Pangenome graph construction from genome alignment with minigraph-cactus” by Glenn Hickey, Jean Monlong, Jana Ebler, Adam M. Novak, Jordan M. Eizenga, Yan Gao, Human Pangenome Reference Consortium, Tobias Marschall, Heng Li and Benedict Paten, 10 May 2023, Nature Biotechnology. DOI: 10.1038/s41587-023-01793-w

Sequencing the last 8% of the human genome has taken 20 years and the invention of new techniques for reading long sequences of the genetic code, which consists of the nucleotides C, T, G and A. The entire genome consists of more than 3 billion nucleotides. Credit: Ernesto del Aguila III, NHGRI Repetitive DNA sequences around centromere show history of human genetic variation. Scientists lied a little when they revealed the entire sequencing of the human genome in 2003. In actuality, almost 20 years later, approximately 8% of the genome has never been completely sequenced, due to highly repetitive DNA segments that are difficult to match with the rest of the genome. However, a three-year-old team has finally filled in the gaps in the remaining DNA, giving scientists and physicians the first complete, gap-free genome sequencing. The recently completed genome, termed T2T-CHM13, is a significant improvement over the existing reference genome, GRCh38, which is used by physicians and scientists to check for disease-linked mutations as well as to study the evolution of human genetic diversity. The new DNA sequences, among other things, provide previously unknown details about the area around the centromere, which is where chromosomes are seized and tugged apart as cells split, ensuring that each “daughter” cell acquires the right amount of chromosomes. Variability within this area might potentially provide fresh information about how our ancestors developed in Africa. “Uncovering the complete sequence of these formerly missing regions of the genome told us so much about how they’re organized, which was totally unknown for many chromosomes,” said Nicolas Altemose, a postdoctoral researcher at the University of California, Berkeley, and co-author of four new articles describing the completed genome. “Before, we just had the blurriest picture of what was there, and now it’s crystal clear down to single base pair resolution.” Altemose is first author of one paper that describes the base pair sequences around the centromere. A paper explaining how the sequencing was done will appear in the April 1 print edition of the journal Science, while Altemose’s centromere paper and four others describing what the new sequences tell us are summarized in the journal with the full papers posted online. Four companion papers, including one for which Altemose is co-first author, also will appear online April 1 in the journal Nature Methods. The sequencing and analysis were performed by a team of more than 100 people, the so-called Telemere-to-Telomere Consortium, or T2T, named for the telomeres that cap the ends of all chromosomes. The consortium’s gapless version of all 22 autosomes and the X sex chromosome is composed of 3.055 billion base pairs, the units from which chromosomes and our genes are built, and 19,969 protein-coding genes. Of the protein-coding genes, the T2T team found about 2,000 new ones, most of them disabled, but 115 of which may still be expressed. They also found about 2 million additional variants in the human genome, 622 of which occur in medically relevant genes. “In the future, when someone has their genome sequenced, we will be able to identify all of the variants in their DNA and use that information to better guide their health care,” said Adam Phillippy, one of the leaders of T2T and a senior investigator at the National Human Genome Research Institute (NHGRI) of the National Institutes of Health. “Truly finishing the human genome sequence was like putting on a new pair of glasses. Now that we can clearly see everything, we are one step closer to understanding what it all means.” The Evolving Centromere The new DNA sequences in and around the centromere total about 6.2% of the entire genome, or nearly 190 million base pairs, or nucleotides. Of the remaining newly added sequences, most are found around the telomeres at the end of each chromosome and in the regions surrounding ribosomal genes. The entire genome is made of just four types of nucleotides, which, in groups of three, code for the amino acids used to build proteins. Altemose’s main research involves finding and exploring areas of the chromosomes where proteins interact with DNA. The spindles (green) that pull chromosomes apart during cell division are attached to a protein complex called the kinetochore, which latches onto the chromosome at a place called the centromere — a region containing highly repetitive DNA sequences. Comparing the sequences of these repeats revealed where mutations have accumulated over millions of years, reflecting the relative age of each repeat. Repeats in the active centromere tend to be the youngest and most recently duplicated sequences in the region, and they have strikingly low DNA methylation. Surrounding the active centromere on both sides are older repeats, probably the relics of former centromeres, with the oldest ones farthest from the active centromere. The researchers hope that new experimental methods will help reveal why centromeres evolve from the middle, as well as why this pattern is so closely associated with binding by the kinetochore and with low DNA methylation. Credit: Nicolas Altemose, UC Berkeley “Without proteins, DNA is nothing,” said Altemose, who earned a Ph.D. in bioengineering jointly from UC Berkeley and UC San Francisco in 2021 after having received a D.Phil. in statistics from Oxford University. “DNA is a set of instructions with no one to read it if it doesn’t have proteins around to organize it, regulate it, repair it when it’s damaged and replicate it. Protein-DNA interactions are really where all the action is happening for genome regulation, and being able to map where certain proteins bind to the genome is really important for understanding their function.” After the T2T consortium sequenced the missing DNA, Altemose and his team used new techniques to find the place within the centromere where a big protein complex called the kinetochore solidly grips the chromosome so that other machines inside the nucleus can pull chromosome pairs apart. “When this goes wrong, you end up with missegregated chromosomes, and that leads to all kinds of problems,” he said. “If that happens in meiosis, that means you can have chromosomal anomalies leading to spontaneous miscarriage or congenital diseases. If it happens in somatic cells, you can end up with cancer — basically, cells that have massive misregulation.” What they found in and around the centromeres were layers of new sequences overlaying layers of older sequences, as if through evolution new centromere regions have been laid down repeatedly to bind to the kinetochore. The older regions are characterized by more random mutations and deletions, indicating they’re no longer used by the cell. The newer sequences where the kinetochore binds are much less variable, and also less methylated. The addition of a methyl group is an epigenetic tag that tends to silence genes. All of the layers in and around the centromere are composed of repetitive lengths of DNA, based on a unit about 171 base pairs long, which is roughly the length of DNA that wraps around a group of proteins to form a nucleosome, keeping the DNA packaged and compact. These 171 base pair units form even larger repeat structures that are duplicated many times in tandem, building up a large region of repetitive sequences around the centromere. The T2T team focused on only one human genome, obtained from a non-cancerous tumor called a hydatidiform mole, which is essentially a human embryo that rejected the maternal DNA and duplicated its paternal DNA instead. Such embryos die and transform into tumors. But the fact that this mole had two identical copies of the paternal DNA — both with the father’s X chromosome, instead of different DNA from both mother and father — made it easier to sequence. The researchers also released this week the complete sequence of a Y chromosome from a different source, which took nearly as long to assemble as the rest of the genome combined, Altemose said. The analysis of this new Y chromosome sequence will appear in a future publication. When the researchers compared centromeric regions of 1,600 people from around the world, they found that those without recent African ancestry mostly had two types of sequence variations. The proportions of these two variations are represented by the black and light gray wedges within the circles, which are placed on the map near the location where each group of individuals was sampled. Those from Africa or other areas with a large proportion of people with recent African ancestry, like the Caribbean, had much more centromeric sequence variation, represented by the multi-colored wedges. Such variations could help track how centromeric regions evolve, as well as how these genetic variants are related to health and disease. Credit: Nicolas Altemose, UC Berkeley Altemose and his team, which included UC Berkeley project scientist Sasha Langley, also used the new reference genome as a scaffold to compare the centromeric DNA of 1,600 individuals from around the world, revealing major differences in both the sequence and copy number of repetitive DNA around the centromere. Previous studies have shown that when groups of ancient humans migrated out of Africa to the rest of the world, they took only a small sample of genetic variants with them. Altemose and his team confirmed that this pattern extends into centromeres. “What we found is that in individuals with recent ancestry outside the African continent, their centromeres, at least on chromosome X, tend to fall into two big clusters, while most of the interesting variation is in individuals who have recent African ancestry,” Altemose said. “This isn’t entirely a surprise, given what we know about the rest of the genome. But what it suggests is that if we want to look at the interesting variation in these centromeric regions, we really need to have a focused effort to sequence more African genomes and do complete telomere-to-telomere sequence assembly.” DNA sequences around the centromere could also be used to trace human lineages back to our common ape ancestors, he noted. “As you move away from the site of the active centromere, you get more and more degraded sequence, to the point where if you go out to the furthest shores of this sea of repetitive sequences, you start to see the ancient centromere that, perhaps, our distant primate ancestors used to bind to the kinetochore,” Altemose said. “It’s almost like layers of fossils.” Long-Read Sequencing a Game Changer The T2T’s success is due to improved techniques for sequencing long stretches of DNA at once, which helps when determining the order of highly repetitive stretches of DNA. Among these are PacBio’s HiFi sequencing, which can read lengths of more than 20,000 base pairs with high accuracy. Technology developed by Oxford Nanopore Technologies Ltd., on the other hand, can read up to several million base pairs in sequence, though with less fidelity. For comparison, so-called next-generation sequencing by Illumina Inc. is limited to hundreds of base pairs. One reason it took 20 years to complete the human genome sequence: much of our DNA is extremely repetitive. Credit: Infographic courtesy of NHGRI, NIH “These new long-read DNA sequencing technologies are just incredible; they’re such game changers, not only for this repetitive DNA world, but because they allow you to sequence single long molecules of DNA,” Altemose said. “You can begin to ask questions at a level of resolution that just wasn’t possible before, not even with short-read sequencing methods.” Altemose plans to explore the centromeric regions further, using an improved technique he and colleagues at Stanford developed to pinpoint the sites on the chromosome that are bound by proteins, similar to how the kinetochore binds to the centromere. This technique, too, uses long-read sequencing technology. He and his group described the technique, called Directed Methylation with Long-read sequencing (DiMeLo-seq), in a paper that appeared this week in the journal Nature Methods. Meanwhile, the T2T consortium is partnering with the Human PanGenome Reference Consortium to work toward a reference genome that represents all of humanity. “Instead of just having one reference from one human individual or one hydatidiform mole, which isn’t even a real human individual, we should have a reference that represents everybody,” Altemose said. “There are various ideas about how to accomplish that. But what we need first is a grasp of what that variation looks like, and we need lots of high-quality individual genome sequences to accomplish that.” His work on the centromeric regions, which he called “a passion project,” was funded by postdoctoral fellowships. The leaders of the T2T project were Karen Miga of UC Santa Cruz, Evan Eichler of the University of Washington, and Adam Phillippy of NHGRI, which provided much of the funding. Other UC Berkeley co-authors of the centromere paper are Aaron Streets, assistant professor of bioengineering; Abby Dernburg and Gary Karpen, professors of molecular and cell biology; project scientist Sasha Langley; and former postdoctoral fellow Gina Caldas. For related research, see Hidden Regions Revealed in First Complete Sequence of a Human Genome. Reference: “Complete genomic and epigenetic maps of human centromeres” by Nicolas Altemose, Glennis A. Logsdon, Andrey V. Bzikadze, Pragya Sidhwani, Sasha A. Langley, Gina V. Caldas, Savannah J. Hoyt, Lev Uralsky, Fedor D. Ryabov, Colin J. Shew, Michael E. G. Sauria, Matthew Borchers, Ariel Gershman, Alla Mikheenko, Valery A. Shepelev, Tatiana Dvorkina, Olga Kunyavskaya, Mitchell R. Vollger, Arang Rhie, Ann M. McCartney, Mobin Asri, Ryan Lorig-Roach, Kishwar Shafin, Julian K. Lucas, Sergey Aganezov, Daniel Olson, Leonardo Gomes de Lima, Tamara Potapova, Gabrielle A. Hartley, Marina Haukness, Peter Kerpedjiev, Fedor Gusev, Kristof Tigyi, Shelise Brooks, Alice Young, Sergey Nurk, Sergey Koren, Sofie R. Salama, Benedict Paten, Evgeny I. Rogaev, Aaron Streets, Gary H. Karpen, Abby F. Dernburg, Beth A. Sullivan, Aaron F. Straight, Travis J. Wheeler, Jennifer L. Gerton, Evan E. Eichler, Adam M. Phillippy, Winston Timp, Megan Y. Dennis, Rachel J. O’Neill, Justin M. Zook, Michael C. Schatz, Pavel A. Pevzner, Mark Diekhans, Charles H. Langley, Ivan A. Alexandrov and Karen H. Miga, 1 April 2022, Science. DOI: 10.1126/science.abl4178

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