Danish reference genome now mapped

Fifty Danish families comprising a mother, father, and child have voluntarily donated blood to the researchers behind the Danish Reference Genome. The reference genome reveals detailed knowledge about genetic variations and deviations specific to the Danish population.

Even though the reference genome is specific to the Danish population, the knowledge is of international interest, as it may increase our understanding of hereditary diseases and promote the development of personalized medicine.

The Danish Reference Genome has been established by GenomeDenmark—a research consortium consisting of DTU, the University of Copenhagen, Aarhus University, and the Beijing Genomics Institute.

Improved understanding of genes and disease

The reference genome is of an extremely high quality and is characterized by an unrivalled depth of information, so far seen only in the international human genome.

Furthermore, the Danish study has—for the first time—thoroughly mapped the non-simple genetic variation among individuals. Knowledge about such variation increases our understanding of how genetic differences affect health and disease development in individuals.

“In our study we have been able to decipher the human genome in 150 healthy Danish individuals at a completely unprecedented scale, and this allows us to identify genetic variation that has never been known before. This is an important step towards understanding the genetics of what makes us human and the differences between us and to improve our understanding of the genetics of disease, but also to further personalize treatments at Danish hospitals,” says Associate Professor Simon Rasmussen, DTU Bioinformatics.

Better identification of cancer genes in children

Associate Professor Ramneek Gupta from DTU Bioinformatics, who is also a member of the project group, explains that the reference genome will provide a shortcut for the gene analysis of Danes in future. Moreover, the reference genome will increase the applicability of other types of gene analyses:

“As national precision medicine programmes emerge around the world, the largest focus is genomics. Now in Denmark, we have the opportunity to use a very high-quality genome reference in our clinical efforts, specific to the Danish population. As we roll out whole genome sequencing for children with cancer all across Denmark, the Danish pan-genome work will prove invaluable for our mapping of genomic variation that predisposes to early cancer.”

DTU Computerome key to research

The vast volumes of data on which the new genetic knowledge is based have been handled by DTU’s supercomputer, the DTU Computerome, the DTU researchers working for the GenomeDenmark consortium explain. In addition to Simon Rasmussen and Ramneek Gupta, they include Associate Professor Jose Izarzugaza and Associate Professor Bent Petersen from DTU Bioinformatics:

“The DTU supercomputer Computerome was absolutely vital in performing the extremely complex computations on piecing together the genomes of these individuals. What really made this a big discovery is that we did not follow the traditional approach of using the human reference genome to identify the genetic variants, but instead assembled the genome of each individual completely from scratch. We started out with the 5 million billion (5*10^16) different letters that make up the human genome (bases) and had to assemble them into the 150 Danish human genomes.”

Link between genes and disease only partially mapped

There is a lot of genetic variation related to the heritability of human diseases that awaits discovery. Therefore, continued research in this field is central for the clinical impact of genomics.

Professor Søren Brunak from the Center for Protein Research at the University of Copenhagen and DTU explains:

“We know that further research is needed to establish causative relations between many of the new genotypes discovered and disease. However, due to the world-class Danish health registers and longitudinal studies, we are uniquely positioned to couple genomics and other types of health data on a large scale in Denmark. And we are heading that way, hoping to be able to keep our ambitions high.”