In 2001, the International Human Genome Sequencing Consortium announced the first draft of the human genome reference sequence. The Human Genome Project, as it was called, had taken more than eleven years of work and involved more than 1000 scientists from 40 countries. This reference, however, did not represent a single individual but instead is a composite of humans that could not accurately capture the complexity of human genetic variation.
Building on this, scientists have carried out many sequencing projects over the last 20 years to identify and catalog genetic differences between an individual and the reference genome. Those differences usually focused on small single base changes and missed larger genetic alterations. Current technologies now are beginning to detect and characterize larger differences — called structural variants — such as insertions of several hundred letters. Structural variants are more likely than smaller genetic differences to interfere with gene function.
An international research team has now published an article inScience announcing a new, considerably more comprehensive reference dataset obtained using a combination of advanced sequencing and mapping technologies. The new reference dataset reflects 64 assembled human genomes, representing 25 different human populations from across the globe. Importantly, each of the genomes was assembled without guidance from the first human genome and as a result better captures genetic differences from different human populations. The study was led by scientists from the European Molecular Biology Laboratory Heidelberg (EMBL), the Heinrich Heine University Düsseldorf (HHU), The Jackson Laboratory for Genomic Medicine in Farmington, Conn. (JAX), and the University of Washington in Seattle (UW).
“With these new reference data, genetic differences can be studied with unprecedented accuracy against the background of global genetic variation, which facilitates the biomedical evaluation of genetic variants carried by an individual,” emphasizes the co-first author of the study, Dr. Peter Ebert from the Institute of Medical Biometry and Bioinformatics at HHU. The distribution of genetic variants can differ substantially between population groups as a result of spontaneous and continuously occurring changes in the genetic material. If such a mutation is passed on over many generations, it can become a genetic variant specific to that population.