Spanish scientists participate in the drafting of a new pangenome more useful for reflecting human diversity

We all carry in our DNA an operating manual, it is our genome. Science has at its disposal a reference map made from very few individuals, which is not sufficient to encompass human genetic diversity, which can only be reflected in a pangenomawhose first draft is published this Wednesday Nature.

This project has involved a large group of researchers, among them Spaniards.led by the International Human Pangenoma Reference Consortium (HPRC).

The director of the Human Genome Reference Program, of which the HPRC is a part, Eric Green, said in a virtual press conference that this is “an incredible scientific achievementwhich provides an expanded view of mankind’s DNA”.

A high quality pangenome, increasingly reflecting the diversity of the human population, will “enable scientists and healthcare professionals to better understand how genomic variants influence health and disease and move toward a future in which genomic medicine benefits everyone,” he said.

Mostly African

The genome is often likened to a book of life that contains the DNA instructions that help each living thing to develop and function, or with a map that reflects where each gene is and what it does.

This first draft of the human pangenome combines the genomic sequences of 47 genetically diverse people and, since each of us has a pair of each chromosome, a total of 94 different sequences have been achieved, Benedict Paten of the University of California at Santa Cruz (USA) has indicated.

Fifty-one percent of these sequences are of origin. African (where the greatest human diversity is found); 34 %. American, 13 % Asian and only 2 % Europeanas the latter was already widely represented in the reference genome available until now.

Target: 700 individuals

The target is to increase to 350 the number of people by mid-2024 and reach 700 sequences by the end of the project.

The pangenome adds to the current 119 million base pairs (the chemical units that make up DNA), which will help researchers study regions of the genome. for which no references previously existed, and “will potentially be able to associate structural variants with disease in future studies,” says a University of California release.

A human reference genome is a consensus gene sequence as a template. When scientists and doctors study an individual’s genome for variations, they compare their DNA to the standard to determine where there are differences.

The first draft of the human genome was submitted in 2001 and the final version was completed a year ago. Its use has made it possible to identify genes involved in specific diseases and to trace the evolution of human traits.

But it was far from perfect, not least because it was constructed from the genetic profile of about twenty people (70% of one) mostly of white and European origin.

The genome of two people is, on average, more than 99 % identical, and are the small differences that contribute to the uniqueness of each one.

Cataloging and understanding the difference

The compression and cataloging of what is distinct “allows us to understand how cells work and their biology, as well as genetic differences and how they contribute to disease,” explained Karen Miga of the University of California.

“We want the future of precision medicine to benefit everyone equally.”

Paten, for his part, has summarized that what is being done. “is redesigning the foundations of genomics. to create a diverse and inclusive representation of human variation as a fundamental reference structure, and thus mitigate bias,” a critical aspect if “we want the future of precision medicine benefits everyone equally.”

The scientist has expressed his appreciation to the extensive team of researchers, among them from the Barcelona Supercomputing Center and the Autonomous University of Barcelona, who have contributed to this project.

With the use of advanced computational techniques to. align the multiple genomic sequences into a single reference.the researchers constructed a pangenome in which each assembly covers more than 99% of the sequence with greater than 99% accuracy.

Whereas the previous reference genome sequence was unique and linear, the pangenome represents many different versions of the sequence at the same time, explains a statement from the National Human Genome Research Institute (USA).

Fundamental to medicine

Universidad Oberta de Catalunya geneticist Salvador Macip has highlighted to EFE. the relevance of the pangenome, which will be useful to study diseases, their prevalence and variants. that can be associated with diseases.

“If, as up to now, you only have variations that are mostly white and European you can’t deduce the same what happens to a person who does not fit this profile“, he said.

The international consortium has focused on both data accessibility and ethical aspects. and the social and legal implications of the project, for which there is a specific group.

These experts work to help guide informed consent, prioritize the study of the various samples, and collaborate with international and indigenous communities. to incorporate their genomic sequences, noted the University of California, Santa Cruz.