Scientists at Amgen deCODE genetics have constructed the first Icelandic pangenome. A new method identifies 6% more genetic variants than previous methods and has already revealed a previously undetected variant associated with a substantially increased risk of Parkinson’s disease.
Scientists at Amgen deCODE genetics have constructed the first Icelandic pangenome to provide a clearer picture of genetic variation in the Icelandic population and its impact on disease risk. The findings are reported in a scientific paper published today in Nature, one of the world’s leading scientific journals. The paper’s first authors are Guillaume Holley and Hannes Pétur Eggertsson, scientists at Amgen deCODE genetics.The Icelandic pangenome can be compared to a detailed map of the genetic material of the population. Instead of representing a single DNA sequence, the map contains multiple sequences and shows how they relate to one another. This provides a clearer picture of genetic diversity between individuals.
The human reference genome was first assembled in 2001 and has since played a central role in genetics research. Such genomes can represent only a single chromosome sequence, or haplotype, assembled from a random selection of many sequenced chromosome sequences. In some cases, this random selection can introduce bias or distortions into genetic analyses.
Pangenomes have been developed to reduce this bias by representing multiple different sequences and the genetic variation between them. However, pangenomes have not yet been widely used, partly because older methods based on the reference genome are simpler and faster to use.
The Icelandic pangenome was constructed from 788 chromosome sequences, of which 698 are Icelandic, and contains more than 50 million genetic variants. No previous reference genome or pangenome has been constructed using genetic material from Icelanders.
Scientists at Amgen deCODE developed new methods to use the pangenome as a reference instead of the conventional reference genome. The new methods were both faster and identified 6% more genetic variants in Icelanders than previous methods. The impact of these variants on disease risk can then be studied.
For example, the researchers identified a variant in the GBA1 gene in Icelanders and people in the UK that had not been detected using previous methods. Icelandic carriers of the variant are more than seven times as likely as others to be diagnosed with Parkinson’s disease before the age of 60.
Daníel Guðbjartsson, Associate Vice President and Site Head at Amgen deCODE genetics, said: “With the Icelandic pangenome, we now have a more accurate map of the genetic material of Icelanders than before. This enables us to identify genetic variants that older methods were unable to detect and to better investigate how they are associated with disease. The aim is to use better genetic information to improve our understanding of the causes of disease and, in doing so, create a stronger foundation for further research.”
The findings indicate that, thanks to these new methods, using pangenomes instead of the conventional reference genome is now a more practical and promising approach. Over time, a more complete understanding of genetic variation could help researchers uncover the biological causes of disease, identify people at greater risk and provide new insights that may inform the development of future medicines.
