2023-05-11 09:49:37
Dhe genome is one of the constitutive elements of humans – so it was a sensation when the first genome was published a good twenty years ago. However, the International Human Genome Project, which started in 1990 and published its reference sequence in 2003, had gaps: it comprised only a good 90 percent of the human genome and consisted of gene sequences from only around 20 people, the majority from one person. After last year in „Science“ An international team of researchers is now preparing to take the logical next step: to develop a reference for the human “pangenome”.
This Wednesday the “Human Pangenome Reference Consortium” published a first draft in the journal “Nature”., which contains genome sequences from 47 genetically diverse individuals. The collection aims to “represent as many DNA sequences as possible found within our species,” according to a press release. It is estimated that the genomes of all human beings are 99.9 percent identical – the remaining per mille makes up all genetic differences. So far, however, the genomes of people of European descent have mainly been used for research purposes. As a result, medical decisions for people from other regions of the world can be based on irrelevant data.
DNA from 350 people
Compared to the previous human reference genome with its approximately three billion base pairs, gaps of 119 million base pairs are now closed and numerous structural variants of the genome are covered. On the other hand, the new project makes it possible to record and map variations between individuals. The results are just an intermediate step: in just over a year, the pangenome should map the genetic diversity of 350 people.
The new reference data should reduce the risk of widening health inequalities, said Eric Green, director of the US government-funded National Human Genome Institute. This is also in line with its goal of increasing diversity in all aspects of genome research, which is crucial to making genome-based medicine usable in a fair way.
The project is made possible by new sequencing technologies that can read longer sections of the genome – previously only short sections could be recorded in one go and the genetic information was then assembled into a genome using algorithms. It is also now possible to read pieces of genome that are not easily accessible due to the cellular packaging of the DNA, or those in which the same sequences are often repeated. The costs for the current project are estimated at around 40 million US dollars, those for the human genome project were estimated at around three billion US dollars.
“First step towards democratization of the genome”
The current publication and that from last year’s “Science” “close practically all the gaps that were still present in the first version of the genome,” explains André Reis, a geneticist who is not involved in the Pangenome project, in a statement. He is director of the Human Genetics Institute at the University Hospital Erlangen. Structural differences in the genome could have a major impact and be relevant to health; its regulatory elements, which “control the orchestra of genes” so to speak, are less well understood. The new project now captures a significant part of the globally existing diversity. “It is an important first step in the democratization of the genome and the participation of people of non-European descent in the achievements of genomic research.”
The project is a start, says Stefan Mundlos, Director of the Institute for Medical Genetics and Human Genetics at the Charité – but: “You will never be able to fully map the full diversity, because many variants are individual.” It will help to identify further associations between diseases and uncover genome. Around a third of patients with a genetic disease can already be diagnosed using the existing reference genome. “This situation should improve with the complete genome,” says Mundlos. The Pangenom project aims to develop new standards at the same time, for the benefit not only of humans. “The methods we are developing should also prove valuable for other species,” the authors write in their article.
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