Unyielding, disregarded segments of human DNA finally cracked and deciphered
The human pangenome project, an ambitious endeavour to capture global genetic variation, has made significant strides, particularly through population-specific efforts and advanced sequencing technologies.
Key developments include the publication of the first Arab human pangenome, a historic milestone achieved in 2025. This study, which analysed the genomes of 53 individuals across eight Arab countries, uncovered millions of previously unknown genetic variants and over 111 million base pairs of DNA missing from prior reference genomes like T2T-CHM13 and GRCh38. This is crucial as Arab populations, representing about 6% of the global population, had been largely underrepresented in genomic databases.
Another significant advancement is the expansion and refinement of global variation catalogues. Researchers reanalysed the 1000 Genomes Project dataset, which covers 1,019 genomes from 26 populations across five continents. Utilising more accurate long-read sequencing, they greatly enhanced maps of structural genomic variation, expanding the previously published human pangenome reference graph by more than twentyfold.
The broader human pangenome effort benefits from ongoing collaboration among international research centres and technological innovation. Projects like the Telomere-to-Telomere Consortium continuously fill gaps in reference sequences, while new AI and machine learning methods accelerate variant interpretation. These advances enable researchers to connect genomic variation with cellular function and disease more effectively.
In 2023, a critical step towards capturing the genetic variation of people around the globe was taken with the mapping and stitching together of the human "pangenome" from the genomes of 47 individuals.
The new data, published in the journal Nature, present what may be the most complete overview of the human genome to date. They create a comprehensive and medically relevant resource that can be used by researchers worldwide to better understand human genomic variation.
Professor Tobias Marschall states that the new data show how human genomic variation is affected by various factors. JAX professor Charles Lee, on the other hand, notes that it was only in the last 3 years that technology has advanced enough to sequence complete genomes.
These advancements mark a transition from an initial general human reference genome to a more comprehensive and inclusive capture of global genomic diversity. Population-specific pangenomes, such as the Arab human pangenome, highlight underrepresented groups and add millions of novel variants, improving the accuracy and utility of genomic references worldwide. Large-scale reanalyses of diverse datasets further refine structural variant catalogues, enhancing our understanding of human genetic diversity and its links to health.
This progress points to an emerging era where global genomic variation is much better represented, though continued efforts are needed to include more populations and fully realize the benefits in research and clinical settings.
References: 1. First Arab Human Pangenome Assembled from 53 Individuals Across Eight Arab Countries 2. Arab Human Pangenome Consortium 3. Expansion and Refinement of Global Variation Catalogs 4. Telomere-to-Telomere Consortium
- Scientific advancements in the field of health and wellness, such as the First Arab Human Pangenome project, are helping to address medical-conditions associated with underrepresented populations by providing a more comprehensive understanding of human genomic variation.
- The expansion and refinement of global variation catalogues, like the one achieved through the Expansion and Refinement of Global Variation Catalogs project, is crucial in the science of health and wellness, as it improves the accuracy of genomic references and aids in the connection between genomic variation and disease.
