The race to complete the human pangenome — which comprises all genetic information across the human species — has been underway since 2022, when the first complete reference human genome sequence was released by the international Telomere-to-Telomere Consortium. Now, a team led by scientists at the Research Organization of Information and Systems has made a significant contribution to a more complete understanding of human genetics with 20 near-complete variant groups located in disease- and immune-related regions from 10 Japanese males.
The work, published on May 27 in Nature Communications , nearly doubled the complete reconstruction rate to 91.2%. According to the research team, this study has implications for better understanding how disease is shaped in the Japanese populations — as well as how to treat disease with personalized medicine.
“We set out to better characterize previously unresolved genomic diversity in the Japanese population, particularly in complex disease- and immune-related regions that are difficult to resolve with conventional reference genomes,” said co-corresponding author Yoshihiko Suzuki, project lecturer at the Research Organization of Information and Systems (ROIS).
Conventional reference genomes don’t necessarily include genetic variations — groups of genes that differ from the majority population, typically inherited from one parent — that contribute to development of certain diseases either through gene mutation or dysfunctional immune response, nor do they include all diversity across populations.
The researchers turned to an approach known as a pangenome graph, which allows the genetic sequences of multiple individuals to be included in one graph. This reveals overlapping sequences and genetic variants in one system, enabling the researchers to identify how genetics converge and diverge across individuals. This information also allows the researchers to detect new variants, and resolve complex and repetitive regions, as well as help mitigate bias in assuming that a limited sample represents an entire group’s genetic diversity.
“We increased the complete reconstruction rate of complex genetic regions related to immunity and disease from the previous 46.8% to 91.2%, and we revealed new genomic sequence structures as well as mutation patterns suggesting bias in the evolutionary process,” Suzuki said.
By reconstructing these previously unresolved genetic regions, the researchers discovered putatively biased gene conversions. In some genomic regions, a process known as gene conversion can take a stretch of DNA sequence from one place and use it to overwrite a similar stretch elsewhere. The putatively biased gene conversions that the researchers found mean that, between certain pairs of genomic segments, this transfer tended to run in only one direction, instead of the two exchanging sequence evenly in both directions. This directional preference occurs even if the results are not evolutionarily beneficial.
“These findings have important implications for understanding what shapes highly complex genomic areas related to immunity and disease,” Suzuki said. “For instance, we found that 13% of the gene conversions in the SMN region — which is associated with spinal muscular atrophy — are potentially biased. This could help us understand how sequence composition, and ultimately this disease, are shaped in the Japanese population.”
Next, the researchers said they plan to integrate these Japanese genome data into global pangenome initiatives.
“Our ultimate goal is to build more accurate pangenome references for precision medicine, evolutionary research and personalized genomic artificial intelligence,” Suzuki said.
Other contributors include co-corresponding author Shinichi Morishita, ROIS; Chie Owa, Haruka Kobayashi and Ryo Nakabayashi, Graduate School of Frontier Sciences, The University of Tokyo; and Brandy McNulty, Ivo Violich, Benedict Paten and Karen H. Miga, UC Santa Cruze Genomics Institute, University of California, Santa Cruz. Suzuki and Morishita were previously affiliated with Graduate School of Frontier Sciences, The University of Tokyo.
The Japan Agency for Medical Research and Development, the Japan Society for the Promotion of Science and the National Institutes of Health supported this work.
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About the Research Organization of Information and Systems (ROIS)
ROIS is a parent organization of four national institutes (National Institute of Polar Research, National Institute of Informatics, the Institute of Statistical Mathematics and National Institute of Genetics) and the Joint Support-Center for Data Science Research. It is ROIS's mission to promote integrated, cutting-edge research that goes beyond the barriers of these institutions, in addition to facilitating their research activities, as members of inter-university research institutes.
Nature Communications
Data/statistical analysis
Cells
Accessing medically relevant complex regions with a pangenome graph of 20 nearcomplete Japanese haplotypes
27-May-2026