The Brazilian Initiative on Precision Medicine (BIPMed): fostering genomic data-sharing of underrepresented populations

Rocha, Cristiane S.; Secolin, Rodrigo; Rodrigues, Maíra R.; Carvalho, Benilton; Lopes-Cendes, Íscia

doi:10.1038/s41525-020-00149-6

Cited by 27 publications

(28 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Databases that specifically focus on specific disease/gene(s) are easier to manage, through which larger genetic databases can be supported, enabling collaboration and data exchange. As a part of the Brazilian Initiative for Precision Medicine (Rocha, Secolin, Rodrigues, Carvalho, & Lopes-Cendes, 2020), the BRCA database, documenting 180 variants in BRCA1 and BRCA2 genes that have been found in the Brazilian population is a first step towards this direction.…”

Section: Discussionmentioning

confidence: 99%

CanVaS: Documenting the genetic variation spectrum of Greek cancer patients

Kalfakakou

Fostira

Papathanasiou

et al. 2021

Preprint

View full text Add to dashboard Cite

National genetic variation registries vastly increase the level of detail for the relevant population, while directly affecting patient management. Herein, we report CanVaS, a Cancer Variation reSource aiming to document the genetic variation of cancer patients in Greece. CanVaS comprises germline genetic data from 7,363 Greek individuals with a personal and/or family history of malignancy. The dataset incorporates ~24,000 functionally annotated rare variants in 97 established or suspected cancer susceptibility genes. For each variant, allele frequency for the Greek population, interpretation for clinical significance, anonymized family and segregation information, as well as phenotypic traits of the carriers, are included. Moreover, information on the geographic distribution of the variants across the country are provided, enabling the study of Greek population isolates. Direct comparisons between Greek (sub)populations with relevant genetic resources is supported, allowing fine-grain localized adjustment of guidelines and clinical decision-making. Most importantly, anonymized data are available for download, while the Leiden Open Variation Database schema is adopted, enabling integration/interconnection with central resources. CanVaS could become a stepping-stone for a countrywide effort to characterize the cancer genetic variation landscape, concurrently supporting national and international cancer research. The database can be accessed at: https://ithaka.rrp.demokritos.gr/CanVaS

show abstract

Section: Discussionmentioning

confidence: 99%

CanVaS: Documenting the genetic variation spectrum of Greek cancer patients

Kalfakakou

Fostira

Papathanasiou

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Accessing the genomic sequences of the general population is relevant to identify the genetic variability involved in the molecular mechanisms of infection 20 . Also, it is known that the admixed Brazilian population is underrepresented in large public databases 21,22 , and previous studies revealed variants present exclusively in Brazilian indivuduals 19,24 .…”

Section: Discussionmentioning

confidence: 99%

“…We studied 27 human COVID-19-related genes and the HLA region in two public genomic databases of admixed Brazilians (BIPMed, www.bipmed.org 19 ; ABraOM http://abraom.ib.usp.br/ 24 ), and additional samples from individuals born in three different towns of south-eastern Brazil. We reported the variants and HLA alleles found in these samples and compared them with worldwide populations.…”

Section: Discussionmentioning

confidence: 99%

“…Brazilian individuals feature an admixed genome, encompassing European, sub-Saharan African, and Native Americans as the three main ancestry populations [15][16][17] , and the distribution of ancestry components varies remarkably throughout the genome 18 . Furthermore, it has been demonstrated that a significant proportion of genetic variability is still undiscovered in admixed Brazilians 19 and that genetic variability may lead to differential response to infection 20 . Therefore, we aim to investigate the genetic variation present in COVID-19 related genes in the Brazilian population.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Genetic variability in COVID-19-related genes in the Brazilian population

Secolin

Araujo

Gonsales

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

SARS-CoV-2 employs the angiotensin-converting enzyme 2 (ACE2) receptor and the transmembrane serine protease (TMPRSS2) to infect human lung cells. Previous studies have suggested that different host genetic backgrounds in ACE2 and TMPRSS2 could contribute to differences in the rate of infection or severity of COVID-19. Recent studies also showed that variants in 15 genes related to type I interferon immunity to influenza virus could predispose to life-threatening COVID-19 pneumonia. Additional genes (SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6, XCR1, IL6, CTSL, ABO, and FURIN) and HLA alleles have also been implicated in response to infection with SARS-CoV-2. Currently, Brazil has recorded the third-highest number of COVID-19 patients worldwide. We aim to investigate the genetic variation present in COVID-19-related genes in the Brazilian population. We analysed 27 candidate genes and HLA alleles in 954 admixed Brazilian exomes. We used the information available in two public databases (http://www.bipmed.org and http://abraom.ib.usp.br/), and additional exomes from individuals born in southeast Brazil, the region with the highest number of COVID-19 patients in the country. Variant allele frequencies were compared with the 1000 Genomes Project phase 3 (1KGP) and the gnomAD databases. We found 395 non-synonymous variants; of these, 325 were also found in the 1000 Genome Project phase 3 (1KGP) and/or gnomAD. Six of these variants were previously reported as putatively influencing the rate of infection or clinical prognosis for COVID-19. The remaining 70 variants were identified exclusively in the Brazilian sample, with a mean allele frequency of 0.0025. In silico prediction of the impact in protein function revealed that three of these rare variants were pathogenic. Furthermore, we identified HLA alleles that were previously associated with COVID-19 response at loci DQB1 and DRB1. Our results showed genetic variability common to other populations, but also rare and ultra-rare variants exclusively found in the Brazilian population. These findings could potentially lead to differences in the rate of infection or response to infection by SARS-CoV-2 and should be further investigated in patients with the disease.

show abstract

“…We evaluated 257 individuals from BIPMed ( Rocha et al, 2020 ), 609 from ABraOM ( Naslavsky et al, 2017 ), and 88 additional exomes from individuals born in the following towns within southeastern Brazil: Barretos ( N = 30); Ribeirão Preto ( N = 30), located in the state of São Paulo; and Belo Horizonte ( N = 28), the capital of the state of Minas Gerais ( Supplementary Figure 1 ). Among individuals included in BIPMed, the birthplace of 193 individuals were included; thus, we were able to extract 21 individuals born in São Paulo city and 37 from Campinas to increase the power of regional comparisons.…”

Section: Methodsmentioning

confidence: 99%

Exploring a Region on Chromosome 8p23.1 Displaying Positive Selection Signals in Brazilian Admixed Populations: Additional Insights Into Predisposition to Obesity and Related Disorders

et al. 2021

Self Cite

View full text Add to dashboard Cite

We recently reported a deviation of local ancestry on the chromosome (ch) 8p23.1, which led to positive selection signals in a Brazilian population sample. The deviation suggested that the genetic variability of candidate genes located on ch 8p23.1 may have been evolutionarily advantageous in the early stages of the admixture process. In the present work, we aim to extend the previous work by studying additional Brazilian admixed individuals and examining DNA sequencing data from the ch 8p23.1 candidate region. Thus, we inferred the local ancestry of 125 exomes from individuals born in five towns within the Southeast region of Brazil (São Paulo, Campinas, Barretos, and Ribeirão Preto located in the state of São Paulo and Belo Horizonte, the capital of the state of Minas Gerais), and compared to data from two public Brazilian reference genomic databases, BIPMed and ABraOM, and with information from the 1000 Genomes Project phase 3 and gnomAD databases. Our results revealed that ancestry is similar among individuals born in the five Brazilian towns assessed; however, an increased proportion of sub-Saharan African ancestry was observed in individuals from Belo Horizonte. In addition, individuals from the five towns considered, as well as those from the ABRAOM dataset, had the same overrepresentation of Native-American ancestry on the ch 8p23.1 locus that was previously reported for the BIPMed reference sample. Sequencing analysis of ch 8p23.1 revealed the presence of 442 non-synonymous variants, including frameshift, inframe deletion, start loss, stop gain, stop loss, and splicing site variants, which occurred in 24 genes. Among these genes, 13 were associated with obesity, type II diabetes, lipid levels, and waist circumference (PRAG1, MFHAS1, PPP1R3B, TNKS, MSRA, PRSS55, RP1L1, PINX1, MTMR9, FAM167A, BLK, GATA4, and CTSB). These results strengthen the hypothesis that a set of variants located on ch 8p23.1 that result from positive selection during early admixture events may influence obesity-related disease predisposition in admixed individuals of the Brazilian population. Furthermore, we present evidence that the exploration of local ancestry deviation in admixed individuals may provide information with the potential to be translated into health care improvement.

show abstract

The Brazilian Initiative on Precision Medicine (BIPMed): fostering genomic data-sharing of underrepresented populations

Cited by 27 publications

References 46 publications

CanVaS: Documenting the genetic variation spectrum of Greek cancer patients

CanVaS: Documenting the genetic variation spectrum of Greek cancer patients

Genetic variability in COVID-19-related genes in the Brazilian population

Exploring a Region on Chromosome 8p23.1 Displaying Positive Selection Signals in Brazilian Admixed Populations: Additional Insights Into Predisposition to Obesity and Related Disorders

Contact Info

Product

Resources

About