The official map of human genes used to study diseases is missing (at least) 40,000 RNA sequences

African American children with asthma are six times more likely to die from complications of the respiratory disease than European children because they do not respond well to bronchodilator treatments. And, in general, Asian and Latin American people are three times more likely to develop lupus—an autoimmune disease—than Europeans. These are two examples of the crucial role our genetic ancestry plays in our risk of developing a disease or in how effectively medications work for us. This is why studying genes is crucial to identifying both the functions they perform and the characteristics they are responsible for. Since the human genome was first sequenced in 2001, scientists have used it as a reference and have created gene maps—highly detailed catalogs that show the position of each human gene and all its functions. The problem is that these maps have been built almost exclusively from data of people of European descent. They are biased and do not represent all of humanity, as revealed for the first time by a study co-led by two Catalan centers, the Barcelona Supercomputing Center - National Supercomputing Center (BSC-CNS) and the Centre for Genomic Regulation (CRG) of Barcelona, ​​and published in Nature Communications"These gene maps, fundamental to biomedical research and used daily by the scientific community, are based on a small sample of humanity," notes Pau Clavell, a researcher at the BSC and the CRG and author of the study. "They have blind spots because they don't include the specific biology of populations from other continents," he emphasizes, adding that this means that RNA molecules—fragments of DNA that genes create to perform a specific function and that are fundamental to biological processes—which could be potentially important in diseases are "invisible" to the scientific community. Discoveries of thousands of new molecules

Catalan researchers analyzed the genetic information of immune cells present in the blood of 43 individuals from eight different human populations: three African, two Asian, two European, and one Native American. They discovered 41,000 new RNA sequences, the vast majority in the genetic material of populations of non-European ancestry. Some of these new sequences appeared in genes related to diseases whose incidence varies among populations, such as lupus, rheumatoid arthritis, asthma, and cholesterol control. "Without these RNA molecules, reference gene maps do not contain key information for understanding why some common diseases act differently in some human groups," notes BSC researcher Marta Melé, senior co-author of the study. They also identified 476 new genes, regions of the genome that were not previously known to produce RNA molecules.

The research was made possible by the specialized artificial intelligence partition of the MareNostrum 5 supercomputer, which allowed them to analyze more than 800 million sequences in 48 hours—a feat impossible with older systems.

With all they have discovered, the researchers have constructed a more accurate, complete, and detailed gene map than the one previously available. This new catalog will allow the study of genetic variants in non-European ancestry, as well as molecular changes that can affect cell function.

In their article, the researchers emphasize that this work is only a first step, because not all ancestry is represented and because they have only studied one type of cell. "Our discovery is just the tip of the iceberg," says Fairlie Reese, a researcher at the BSC.

Scientists also urge the international scientific community to "strive for equity in genomics to create precision medicine that is equal and fair for all." "Inclusivity in genomic studies is beneficial for everyone, because throughout history humanity has moved from place to place, there has always been genetic exchange everywhere, and therefore [genetic ancestry] is not black and white, or even a grayscale, but rather a continuum." "You can have RNA molecules more similar to those of most Africans than to those of most Europeans."