A genomic database of elderly people in São Paulo, developed by researchers at the Center for the Study of Human Genomes and Stem Cells, at the Institute of Biosciences at the University of São Paulo, will make it possible to identify mutations responsible for genetic diseases in the Brazilian population or that are determinants of healthy aging.
Individual data are now available to the scientific community upon download request. Aggregates began to be made available in recent years in the Brazilian On-line Archive of Mutations (ABraOM).
Results obtained through analyzes made from the genomic bank were described in an article published this Friday (4) in the journal Nature Communications. The preliminary findings were published in 2020 on the bioRxiv platform, in an article without peer review.
“Since the data became available, several accesses by researchers from Brazil and abroad have been registered to the repository. This demonstrates the importance of this initiative for the scientific community,” said researcher Mayana Zatz, a professor at USP and coordinator of the research center funded by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP).
The bank is the result of a pioneering study of the sequencing of 1,171 complete genomes of elderly Brazilians, representing the largest group of genomes of elderly people in Latin America.
The research, initially called “Projeto 80mais”, was started in 2008 with the objective of characterizing the genome of healthy elderly people from a physical and cognitive point of view, with the aim of creating a genomic reference bank for the Brazilian population and contributing to the to unravel the factors involved with healthy aging.
With a mean age of 71 years and not related, the elderly were selected by researchers from the Faculty of Public Health at USP within the scope of the Health, Well-being and Aging Project (Sabe), supported by FAPESP.
Started in 2000 and coordinated by professors Maria Lúcia Lebrão and Yeda Duarte, the project aims to profile the living and health conditions of elderly people living in the city of São Paulo and in other urban centers in Latin America and the Caribbean to from household interviews, assessments and medical examinations.
“The study is representative of the elderly population of São Paulo because it is based on the census of the city of São Paulo and includes people of all socioeconomic levels”, evaluates Mayana.
highly mixed population
The elderly were chosen as the target population for genome sequencing because they are past the age of onset of a series of diseases that appear in old age, such as Alzheimer’s and Parkinson’s, among others.
The fact that they live in São Paulo, the largest metropolis in the country, also allowed them to represent the genetic diversity of the Brazilian population, which is highly mixed, says Mayana.
“São Paulo is the most mixed-race city in Brazil, because it brings together descendants of immigrants from different continents, such as Europe, Asia and Africa, in addition to people born in several other states and countries”, evaluates the researcher.
This high genetic diversity of the elderly in São Paulo participating in the study will fill the gap of the low representation of highly mixed populations in international genomic banks, based predominantly on the European population, the study authors point out.
The researchers identified, for example, about 2 million genetic variants in the elderly in São Paulo that were not previously described in international genomic databases.
“This is related to the fact that international genomic banks portray more of the European reference genome. It is possible that this number of 2 million new genetic variants that we found will decrease as these repositories include populations that are underrepresented, such as the Brazilian one”, estimates Michel Naslavsky, professor at USP and first author of the study.
The increase in diversity in international genomic banks will also make it possible to improve the accuracy of genetic tests for highly mixed populations, such as Brazil and other Latin American countries, in general, according to the researchers.
Analyzes carried out on the genomes of the elderly who are part of the Brazilian genomic bank revealed that they carry, for example, genetic variants classified in European genomic banks as pathogenic, but that they do not manifest the diseases related to these mutations.
“One of the hypotheses that we are raising for this is that genetic variants hitherto classified as pathogenic can be expressed differently according to the individual’s genetic background, such as European or mixed race”, says Naslavsky.
The researchers also found that elderly Brazilians carry variants associated with recessive diseases common in both Europeans and Africans, such as cystic fibrosis. The frequency of heterozygous people – carriers of a recessive variant – allows estimating the incidence of these diseases in the population.
“In the case of the Brazilian population, we estimate that the incidence of cystic fibrosis is one case in every 10,000 births. This information is very important for public genetic counseling programs for couples of reproductive age in relation to the risks of having children with serious genetic diseases”, evaluates Zatz.
Through the analysis of the genomic data of the elderly, it was also possible to identify new variants of immune system genes (HLA), which encode important proteins in the immune response by allowing the recognition of pathogens.
According to the researchers, these genes are known to be the most variable and diverse in the human species, which makes them difficult to analyze.
Through the application of a specialized technique to describe these genes, more than 140 combinations have never been described. These findings are important for studies on susceptibility or resistance to infections by various pathogens, including SARS-CoV-2, they stress.