Brazil launches genetic screening project for prospective parents

In the coming weeks, the Human Genome and Stem Cell Research Center (HUG-CELL) will begin recruiting participants for the "Our Genes" project. The initiative aims to identify couples at an increased risk of transmitting recessive genetic disorders, where a child inherits two altered copies of the same gene, one from each parent, as well as Fragile X syndrome, a common cause of intellectual disability that is passed down through families.

The work will be carried out in partnership with the University of Brasília (UnB), the Federal University of Bahia (UFBA), the Federal University of Espírito Santo (UFES), and other collaborators. Michel Satya Naslavsky, a researcher at HUG-CELL – a FAPESP Research, Innovation, and Dissemination Center (RIDC) based at the Institute of Biosciences of the University of São Paulo (USP) – presented the scope of the initiative during FAPESP Week London.

Couples planning to have children can voluntarily sign up for screening of genes associated with recessive disorders and Fragile X syndrome. If both carry pathogenic variants in the same gene, presenting a 25% risk of conceiving an affected child, they'll be informed during genetic counseling." 

Michel Satya Naslavsky, researcher at HUG-CELL – a FAPESP Research, Innovation, and Dissemination Center (RIDC) 

In addition to helping people make informed decisions about having children, the project aims to create a large genetic database for Brazil. The goal is to determine the prevalence of hereditary genetic diseases and create "risk calculators." These calculators aggregate various small variations in a person's DNA to predict their likelihood of developing common diseases such as diabetes, high blood pressure, and heart problems. This is important because most current research uses data from Europeans, which does not accurately represent the genetic diversity of the Brazilian population.

"The UK Biobank [the largest health database available to researchers, which tracks the genetics and lifestyles of 500,000 British volunteers so that global researchers can investigate the causes of disease and develop treatments] is an incredible resource, but 90% of its database consists of individuals of European ancestry. None of the remaining 10% represent profiles similar to those of Brazilians," he said.

This gap is critical because polygenic risk scores, which aggregate thousands of small DNA variations to predict susceptibility to common diseases, vary drastically depending on ancestry. Since current global models do not account for Brazil's intense genetic mixing, Naslavsky explained that they often underestimate or overestimate risks when applied to the Brazilian population.

"When trying to diagnose rare diseases, the lack of data on non-European genetic fragments in global databases, such as ClinVar [a public repository of human genetic variants], makes the chance of a correct diagnosis three times lower for non-European regions of the genome," he noted.

Urgent need

The inability to import models developed abroad makes creating national genetic databases an urgent necessity. This will ensure that precision medicine effectively reaches the SUS (Brazil's national public health network). "There's no way around it. We need to generate data from Brazilians because we won't be able to use borrowed information," Naslavsky emphasized.

To bridge this gap, HUG-CELL created the Brazilian Online Mutation Archive (ABraOM) in 2017. This public database has become an essential tool for scientists and laboratories because it helps identify which genetic variations are common in the Brazilian population and do not cause disease. Since the archive was built using data from healthy older adults, it functions as a highly precise filter. If a mutation appears in the archive, doctors know it is harmless, allowing them to focus their search on other potential causes. "With 1,170 genomes, it remains the largest public, census-based genomic database in the country," he stated.

To scale up genomic mapping, the Ministry of Health launched the Genoma SUS project in 2023. Like the "Our Genes" initiative, it is linked to the Genomas Brasil Program. The Genoma SUS effort brings together nine research laboratories across all regions of Brazil and has already sequenced 21,000 complete genomes. The goal is to sequence another 50,000 genomes over the next two years. FAPESP is funding 15,000 of these analyses in the state of São Paulo.

"Brazil has the largest public and universal health system in the world. It makes sense for the SUS to make this investment so that the technology can be incorporated here without relying on data produced abroad," the researcher argued.

Data sovereignty

A central point in Naslavsky's vision is sovereignty. The researcher advocates a management model in which returns from research are prioritized for the public health system and researchers with public health-focused projects.

"From a moral standpoint, who benefits most from this data? The SUS. It makes perfect sense for the government to make this investment," he stated. Beyond its immediate impact on diagnostic workflows and other applications, such as identifying at-risk couples, generating Brazilian data enables unprecedented discoveries. Naslavsky cited studies on Alzheimer's disease and lipid metabolism variants, noting that Brazil's mixed-race population may reveal alternative biological pathways that could lead to new therapeutic targets.

"Studying our population isn't only important for understanding our risks; it's an opportunity to discover biological mechanisms that could benefit the whole world," he concluded.