An international team of scientists, including researchers from the Norman Lab at the University of Colorado Anschutz Medical Campus (CU Anschutz), has created one of the most complete and inclusive maps of the human genome to date. Published in Nature, the study involved sequencing the DNA of 65 individuals from diverse global populations and generating 130 genome assemblies. Each assembly provides a detailed and accurate view of a person’s genetic code, helping to capture the full range of human genetic diversity.
Why is this important? Until now, the reference genome used by scientists was based on just a few individuals. That meant many genetic differences were missing, especially those found in people from underrepresented populations. This new “pangenome” includes a much broader range of human diversity, helping researchers better understand how our genes vary and how those differences may relate to health and disease.
“By focusing on the most complicated parts of the human genome, such as the MHC that houses the HLA genes, this study encompasses those regions most commonly associated with complex diseases,” said Paul Norman, PhD, professor of biomedical informatics, who contributed to the study. “These genes are implicated in multiple immune-mediated diseases, including autoimmunity, allergy, infection, and some cancers, as well as their treatments, including transplantation and specific immunotherapies. They are also implicated in modulation of effective placentation. The resource is relevant to a huge range of clinicians and scientists on campus.”
Filling in the Blanks
The team was able to close 92% of the gaps found in earlier genome maps and fully completed 39% of all chromosomes from end to end. That includes some of the most complex and medically important regions of our DNA, such as:
- The MHC region, which plays a key role in immune response.
- Genes like SMN1/SMN2, linked to spinal muscular atrophy.
- AMY1/AMY2, which helps digest starch.
They also fully mapped 1,246 centromeres, the central parts of chromosomes essential for cell division, and discovered surprising variation in their structure, which could have implications for understanding certain diseases.
A New Era for Genetic Research
By combining this new data with earlier drafts of the pangenome, scientists can now detect over 26,000 structural differences in DNA per person, many of which were previously invisible. This level of detail allows for more precise genetic testing and a deeper understanding of how our genes affect health and disease.
The study marks a significant advance in genomic research and a meaningful step toward more inclusive and precise medicine. The potential impact includes:
- Improving the accuracy of genetic testing for people of all backgrounds.
- Enabling better diagnosis and treatment of rare and complex diseases.
- Enhancing research into conditions like autoimmune disorders, neurological diseases and cancer.
- Supporting more equitable participation in precision medicine and clinical trials.
“Because we had developed cost-effective methods to analyze the HLA and MHC at high resolution and through our ongoing goal, in collaboration with the Dilthey group from Düsseldorf in Germany, to increase the diversity of genomic references, we were asked to contribute to the study,” said Nicholas Pollock, postdoctoral candidate in human medical genetics and genomics. “We are now making the high-resolution genotyping methods available to anyone on campus who is interested in the role of HLA and MHC in human health and disease.”
This research helps pave the way for more precise and effective medical care that better accounts for the genetic differences across global populations.
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