This reference data includes individuals from all over the world to better capture the genetic diversity of the human species.
Among other applications, the work, published in the journal Science, enables population-specific studies on genetic predispositions to human diseases as well as the discovery of more complex forms of genetic variation.
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 11 years of work and involved more than 1,000 scientists from 40 countries.
This reference, however, did not represent a single individual but instead was a composite of humans, and that approach could not accurately capture the complexity of human genetic variation.
Researchers published the 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, said the study.
The study was led by scientists from the European Molecular Biology Laboratory Heidelberg (EMBL), the Heinrich Heine University Dusseldorf (HHU) in Germany, The Jackson Laboratory for Genomic Medicine in Farmington, Connecticut (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,” said co-first author of the study, 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.
The new reference data provide an important basis for including the full spectrum of genetic variants in so-called genome-wide association studies.
The aim is to estimate the individual risk of developing certain diseases such as cancer and to understand the underlying molecular mechanisms, said the study.
This, in turn, can be used as a basis for more targeted therapies and preventative medicine.
Thus, this work might enable further applications in precision medicine.
Drug efficacy, for example, can vary between individuals based on their genomes. The new reference data now represent the full range of different genetic variant types and incorporates human genomes of great diversity.
Therefore, this new resource might contribute to developing novel approaches in personalised medicine, where the selection of therapies is tailored to a patient’s individual genetic background.
This study builds on a new method published by these researchers last year in Nature Biotechnology to accurately reconstruct the two components of a person’s genome – one inherited from a person’s father, one from a person’s mother.
When assembling a person’s genome, this method eliminates the potential biases that could result from comparisons with an imperfect reference genome.