Every person’s complete DNA has been compared to a template that is largely based on genetic material from one man, who has been referred to as “the guy from Buffalo” by scientists for the past two decades.
However, they have known for a long time that the “reference genome,” or template for comparison, lacks the full range of human diversity, which severely limits its use.
Benedict Paten, a specialist in genomics from the University of California, Santa Cruz, stated, “We need a really good understanding of the variations and the differences between human beings.” We are being left out.”
Now, scientists are creating a reference that is much more diverse, which they call a “pangenome,” and it includes the genetic material of 47 people from all over the world. Four studies on the topic were published on Wednesday in Nature and Nature Biotechnology. It should help patients in the future, according to scientists, who claim that it is already teaching them new things about health and disease.
According to Paten, the new reference should help scientists better understand what is normal and what isn’t. We won’t be able to say, “Oh, this big structural variation that affects this gene?” until we understand what common variation looks like. He said, “Don’t worry about it.”
Experts define a pangenome as a collection of whole genome sequences from many people intended to represent the genetic diversity of the human species. A human genome is the set of instructions for building and maintaining a human being. The pangenome is certainly not a composite yet an assortment; researchers portray it as a rainbow of stacked genomes, contrasted, with one line addressing the more seasoned, single reference genome.
The Human Pangenome Project builds on the first sequencing of the entire human genome, which was almost finished more than two decades ago and was finally completed last year. According to Paten, a project leader and author of the pangenome study, an African American man of mixed African and European ancestry who responded to a Buffalo newspaper ad for volunteers in 1997 provided 70% of the first reference genome. A group of around twenty people accounted for about 30%.
The pangenome contains material from 24 individuals of African lineage, 16 from the Americas and the Caribbean, six from Asia, and one from Europe.
According to Paten, “it’s those differences that are the things that genetics and genomics are concerned with studying and understanding,” despite the fact that the genomes of any two people are more than 99 percent identical.
Patients may not experience immediate benefits from the research for some time. However, new insights, according to scientists, should eventually increase the accuracy of genetic testing, enhance drug discovery, and support personalized medicine, which makes use of an individual’s individual genetic profile to guide decisions regarding the prevention, diagnosis, and treatment of disease.
Dr. Wendy Chung, a clinical genetics expert at Columbia University who was not involved in the research, stated that “The Pangenome Project gives a more accurate representation of the genome of people from around the world” and that it ought to assist physicians in making more accurate diagnoses of genetic conditions.
The rainbow of references could be used to compare a person’s gene variation.
According to study author Evan Eichler of the University of Washington, researchers will also learn more about genes that have already been linked to issues, such as a gene linked to African American cardiovascular disease.
He stated, “Now that we can actually sequence that gene in its entirety and understand the variation in that gene, we can start to go back to unexplained cases of patients with coronary heart disease” and examine them in light of the new information. Eichler is paid by the Howard Hughes Clinical Organization, which likewise upholds The Related Press’ wellbeing and science division.
Candice Hirsch, an expert in plant genetics at the University of Minnesota who was not involved in the research but has closely followed it, said that she anticipates that many new discoveries will result from it. “We really have only been able to scratch the surface of understanding the genetics that underlies disease,” has been her statement up until this point.
The consortium driving the examination is important for the Human Genome Reference Program, which is financed by an arm of the U.S. Public Establishments of Wellbeing.
With the intention of having sequences from 350 individuals by the middle of the coming year, the team is currently adding to the collection of reference genomes. Additionally, scientists hope to collaborate more with international partners, including Indigenous population-focused ones.
Paten stated, “We’re in it for the long game.”
More information: Benedict Paten et al, A draft human pangenome reference, Nature Biotechnology (2023). DOI: 10.1038/s41586-023-05896-x. www.nature.com/articles/s41586-023-05896-x
Vollger et al, Increased mutation rate and gene conversion within human segmental duplications, Nature (2023). DOI: 10.1038/s41586-023-05895-y
Guarracino et al, Recombination between heterologous human acrocentric chromosomes, Nature (2023). DOI: 10.1038/s41586-023-05976-y