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  1. Article: A review of ancestrality and admixture in Latin America and the caribbean focusing on native American and African descendant populations.

    De Oliveira, Thais C / Secolin, Rodrigo / Lopes-Cendes, Iscia

    Frontiers in genetics

    2023  Volume 14, Page(s) 1091269

    Abstract: Genomics can reveal essential features about the demographic evolution of a population that may not be apparent from historical elements. In recent years, there has been a significant increase in the number of studies applying genomic epidemiological ... ...

    Abstract Genomics can reveal essential features about the demographic evolution of a population that may not be apparent from historical elements. In recent years, there has been a significant increase in the number of studies applying genomic epidemiological approaches to understand the genetic structure and diversity of human populations in the context of demographic history and for implementing precision medicine. These efforts have traditionally been applied predominantly to populations of European origin. More recently, initiatives in the United States and Africa are including more diverse populations, establishing new horizons for research in human populations with African and/or Native ancestries. Still, even in the most recent projects, the under-representation of genomic data from Latin America and the Caribbean (LAC) is remarkable. In addition, because the region presents the most recent global miscegenation, genomics data from LAC may add relevant information to understand population admixture better. Admixture in LAC started during the colonial period, in the 15th century, with intense miscegenation between European settlers, mainly from Portugal and Spain, with local indigenous and sub-Saharan Africans brought through the slave trade. Since, there are descendants of formerly enslaved and Native American populations in the LAC territory; they are considered vulnerable populations because of their history and current living conditions. In this context, studying LAC Native American and African descendant populations is important for several reasons. First, studying human populations from different origins makes it possible to understand the diversity of the human genome better. Second, it also has an immediate application to these populations, such as empowering communities with the knowledge of their ancestral origins. Furthermore, because knowledge of the population genomic structure is an essential requirement for implementing genomic medicine and precision health practices, population genomics studies may ensure that these communities have access to genomic information for risk assessment, prevention, and the delivery of optimized treatment; thus, helping to reduce inequalities in the Western Hemisphere. Hoping to set the stage for future studies, we review different aspects related to genetic and genomic research in vulnerable populations from LAC countries.
    Language English
    Publishing date 2023-01-19
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2606823-0
    ISSN 1664-8021
    ISSN 1664-8021
    DOI 10.3389/fgene.2023.1091269
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The Brazilian Initiative on Precision Medicine (BIPMed): fostering genomic data-sharing of underrepresented populations.

    Rocha, Cristiane S / Secolin, Rodrigo / Rodrigues, Maíra R / Carvalho, Benilton S / Lopes-Cendes, Iscia

    NPJ genomic medicine

    2020  Volume 5, Page(s) 42

    Abstract: The development of precision medicine strategies requires prior knowledge of the genetic background of the target population. However, despite the availability of data from admixed Americans within large reference population databases, we cannot use ... ...

    Abstract The development of precision medicine strategies requires prior knowledge of the genetic background of the target population. However, despite the availability of data from admixed Americans within large reference population databases, we cannot use these data as a surrogate for that of the Brazilian population. This lack of transferability is mainly due to differences between ancestry proportions of Brazilian and other admixed American populations. To address the issue, a coalition of research centres created the Brazilian Initiative on Precision Medicine (BIPMed). In this study, we aim to characterise two datasets obtained from 358 individuals from the BIPMed using two different platforms: whole-exome sequencing (WES) and a single nucleotide polymorphism (SNP) array. We estimated allele frequencies and variant pathogenicity values from the two datasets and compared our results using the BIPMed dataset with other public databases. Here, we show that the BIPMed WES dataset contains variants not included in dbSNP, including 6480 variants that have alternative allele frequencies (AAFs) >1%. Furthermore, after merging BIPMed WES and SNP array data, we identified 809,589 variants (47.5%) not present within the 1000 Genomes dataset. Our results demonstrate that, through the incorporation of Brazilian individuals into public genomic databases, BIPMed not only was able to provide valuable knowledge needed for the implementation of precision medicine but may also enhance our understanding of human genome variability and the relationship between genetic variation and disease predisposition.
    Language English
    Publishing date 2020-10-02
    Publishing country England
    Document type Journal Article
    ZDB-ID 2813848-X
    ISSN 2056-7944 ; 2056-7944
    ISSN (online) 2056-7944
    ISSN 2056-7944
    DOI 10.1038/s41525-020-00149-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Slowly progressive behavioral frontotemporal dementia syndrome in a family co-segregating the C9orf72 expansion and a Synaptophysin mutation.

    Prota, Joana / Rizzi, Liara / Bonadia, Luciana / de Souza, Leonardo Cruz / Caramelli, Paulo / Secolin, Rodrigo / Lopes-Cendes, Iscia / Balthazar, Marcio L F

    Alzheimer's & dementia : the journal of the Alzheimer's Association

    2021  Volume 18, Issue 3, Page(s) 523–528

    Abstract: Introduction: Synaptophysin, already related to X-linked intellectual disability, is expressed mainly in the central nervous system. Studies in humans indicate that the downregulation of synaptophysin could be involved in the development of dementia. ... ...

    Abstract Introduction: Synaptophysin, already related to X-linked intellectual disability, is expressed mainly in the central nervous system. Studies in humans indicate that the downregulation of synaptophysin could be involved in the development of dementia. Our study presents the first familial case of behavioral variant frontotemporal dementia associated with the co-occurrence of the repeat expansion in C9orf72 and a pathogenic variant in the SYP gene.
    Methods: Exome sequencing and repeat-primed PCR for C9orf72 were performed for two siblings with clinical and imaging findings suggestive of slowly progressive behavioral frontotemporal dementia.
    Results: We found that both siblings have the hexanucleotide expansion in C9orf72 and a null variant in the SYP gene. The most affected sibling presents the putative variant in a hemizygous state. With milder symptoms, his sister has the same pathogenic variant in heterozygosis, compatible with X-linked inheritance.
    Discussion: Our results strengthened previous suggestive evidence that the phenotypes associated with C9orf72 repeat expansion are variable and probably influenced by additional genetic modifiers. We hypothesized that the pathogenic variant in the SYP gene might have modified the typical phenotype associated with the C9orf72 mutation.
    MeSH term(s) Amyotrophic Lateral Sclerosis/genetics ; Amyotrophic Lateral Sclerosis/pathology ; C9orf72 Protein/genetics ; DNA Repeat Expansion/genetics ; Frontotemporal Dementia/genetics ; Humans ; Mutation/genetics ; Proteins/genetics ; Synaptophysin/genetics
    Chemical Substances C9orf72 Protein ; C9orf72 protein, human ; Proteins ; Synaptophysin
    Language English
    Publishing date 2021-07-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2211627-8
    ISSN 1552-5279 ; 1552-5260
    ISSN (online) 1552-5279
    ISSN 1552-5260
    DOI 10.1002/alz.12409
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  4. Article ; Online: Association and interaction of genetic variants with occurrence of ischemic stroke among Brazilian patients.

    Ferreira, Leslie Ecker / Secolin, Rodrigo / Lopes-Cendes, Iscia / Cabral, Norberto Luiz / França, Paulo Henrique Condeixa de

    Gene

    2019  Volume 695, Page(s) 84–91

    Abstract: Ischemic Stroke (IS) is a severe and complex disorder of high morbidity and mortality rates associated with clinical, environmental, and genetic predisposing factors. Despite previous studies have associated genetic variants to stroke, inconsistent ... ...

    Abstract Ischemic Stroke (IS) is a severe and complex disorder of high morbidity and mortality rates associated with clinical, environmental, and genetic predisposing factors. Despite previous studies have associated genetic variants to stroke, inconsistent results from different populations pointed to the genetic heterogeneity for IS. Therefore, we may hypothesize that an interaction effect among genetic variants could contribute to IS occurrence rather than genetic variants independently. In this context, we investigated the association and interaction between genetic variants and large-artery atherosclerosis IS (LAAS-IS) and cardioembolic IS (CE-IS). We genotyped 435 patients (195 LAAS-IS; 240 CE-IS) and 535 controls from a population of Joinville, Santa Catarina, Brazil. Association and interaction analysis were performed by chi-square test and Multifactor-dimensionality Reduction test. We found an association between rs2383207*A allele, nearby CDKN2B-AS1, and LAAS-IS [OR 2.35 (95% CI = 1.79-3.08); p = 4.66 × 10
    MeSH term(s) Aged ; Atherosclerosis/genetics ; Atherosclerosis/physiopathology ; Brain Ischemia/epidemiology ; Brain Ischemia/genetics ; Brain Ischemia/physiopathology ; Brazil/epidemiology ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genotype ; Humans ; Logistic Models ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; RNA, Long Noncoding/genetics ; Risk Factors ; Stroke/epidemiology ; Stroke/genetics ; Stroke/physiopathology
    Chemical Substances CDKN2B antisense RNA, human ; RNA, Long Noncoding
    Language English
    Publishing date 2019-02-08
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 391792-7
    ISSN 1879-0038 ; 0378-1119
    ISSN (online) 1879-0038
    ISSN 0378-1119
    DOI 10.1016/j.gene.2019.01.041
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  5. Article ; Online: New avenues in molecular genetics for the diagnosis and application of therapeutics to the epilepsies.

    Magalhães, Pedro H M / Moraes, Helena T / Athie, Maria C P / Secolin, Rodrigo / Lopes-Cendes, Iscia

    Epilepsy & behavior : E&B

    2019  Volume 121, Issue Pt B, Page(s) 106428

    Abstract: Genetic epidemiology studies have shown that most epilepsies involve some genetic cause. In addition, twin studies have helped strengthen the hypothesis that in most patients with epilepsy, a complex inheritance is involved. More recently, with the ... ...

    Abstract Genetic epidemiology studies have shown that most epilepsies involve some genetic cause. In addition, twin studies have helped strengthen the hypothesis that in most patients with epilepsy, a complex inheritance is involved. More recently, with the development of high-density single-nucleotide polymorphism (SNP) microarrays and next-generation sequencing (NGS) technologies, the discovery of genes related to the epilepsies has accelerated tremendously. Especially, the use of whole exome sequencing (WES) has had a considerable impact on the identification of rare genetic variants with large effect sizes, including inherited or de novo mutations in severe forms of childhood epilepsies. The identification of pathogenic variants in patients with these childhood epilepsies provides many benefits for patients and families, such as the confirmation of the genetic nature of the diseases. This process will allow for better genetic counseling, more accurate therapy decisions, and a significant positive emotional impact. However, to study the genetic component of the more common forms of epilepsy, the use of high-density SNP arrays in genome-wide association studies (GWAS) seems to be the strategy of choice. As such, researchers can identify loci containing genetic variants associated with the common forms of epilepsy. The knowledge generated over the past two decades about the effects of the mutations that cause the monogenic epilepsy is tremendous; however, the scientific community is just starting to apply this information in order to generate better target treatments.
    MeSH term(s) Epilepsy/diagnosis ; Epilepsy/genetics ; Epilepsy/therapy ; Genome-Wide Association Study ; High-Throughput Nucleotide Sequencing ; Humans ; Molecular Biology ; Mutation/genetics
    Language English
    Publishing date 2019-08-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2010587-3
    ISSN 1525-5069 ; 1525-5050
    ISSN (online) 1525-5069
    ISSN 1525-5050
    DOI 10.1016/j.yebeh.2019.07.029
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  6. Article: Increased runs of homozygosity in the autosomal genome of Brazilian individuals with neurodevelopmental delay/intellectual disability and/or multiple congenital anomalies investigated by chromosomal microarray analysis.

    Correia-Costa, Gabriela Roldão / Sgardioli, Ilária Cristina / Santos, Ana Paula Dos / Araujo, Tânia Kawasaki de / Secolin, Rodrigo / Lopes-Cendes, Iscia / Gil-da-Silva-Lopes, Vera Lúcia / Vieira, Társis Paiva

    Genetics and molecular biology

    2022  Volume 45, Issue 1, Page(s) e20200480

    Abstract: Runs of homozygosity (ROH) in the human genome may be clinically relevant. The aim of this study was to report the frequency of increased ROH of the autosomal genome in individuals with neurodevelopmental delay/intellectual disability and/or multiple ... ...

    Abstract Runs of homozygosity (ROH) in the human genome may be clinically relevant. The aim of this study was to report the frequency of increased ROH of the autosomal genome in individuals with neurodevelopmental delay/intellectual disability and/or multiple congenital anomalies, and to compare these data with a control group. Data consisted of calls of homozygosity from 265 patients and 289 controls. In total, 7.2% (19/265) of the patients showed multiple ROH exceeding 1% of autosomal genome, compared to 1.4% (4/289) in the control group (p=0.0006). Homozygosity ranged from 1.38% to 22.12% among patients, and from 1.53 to 2.40% in the control group. In turn, 1.9% (5/265) of patients presented ROH ≥10Mb in a single chromosome, compared to 0.3% (1/289) of individuals from the control group (p=0.0801). By excluding cases with reported consanguineous parents (15/24), the frequency of increased ROH was 3.4% (9/250) among patients and 1.7% (5/289) in the control group, considering multiple ROH exceeding 1% of the autosome genome and ROH ≥10Mb in a single chromosome together, although not statistically significant (p=0.1873). These results reinforce the importance of investigating ROH, which with complementary diagnostic tests can improve the diagnostic yield for patients with such conditions.
    Language English
    Publishing date 2022-02-28
    Publishing country Brazil
    Document type Journal Article
    ZDB-ID 1445712-x
    ISSN 1678-4685 ; 1415-4757
    ISSN (online) 1678-4685
    ISSN 1415-4757
    DOI 10.1590/1678-4685-GMB-2020-0480
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  7. Article: Association Analysis of Candidate Variants in Admixed Brazilian Patients With Genetic Generalized Epilepsies.

    Kaibara, Felipe S / de Araujo, Tânia K / Araujo, Patricia A O R A / Alvim, Marina K M / Yasuda, Clarissa L / Cendes, Fernando / Lopes-Cendes, Iscia / Secolin, Rodrigo

    Frontiers in genetics

    2021  Volume 12, Page(s) 672304

    Abstract: Genetic generalized epilepsies (GGEs) include well-established epilepsy syndromes with generalized onset seizures: childhood absence epilepsy, juvenile myoclonic epilepsy (JME), juvenile absence epilepsy (JAE), myoclonic absence epilepsy, epilepsy with ... ...

    Abstract Genetic generalized epilepsies (GGEs) include well-established epilepsy syndromes with generalized onset seizures: childhood absence epilepsy, juvenile myoclonic epilepsy (JME), juvenile absence epilepsy (JAE), myoclonic absence epilepsy, epilepsy with eyelid myoclonia (Jeavons syndrome), generalized tonic-clonic seizures, and generalized tonic-clonic seizures alone. Genome-wide association studies (GWASs) and exome sequencing have identified 48 single-nucleotide polymorphisms (SNPs) associated with GGE. However, these studies were mainly based on non-admixed, European, and Asian populations. Thus, it remains unclear whether these results apply to patients of other origins. This study aims to evaluate whether these previous results could be replicated in a cohort of admixed Brazilian patients with GGE. We obtained SNP-array data from 87 patients with GGE, compared with 340 controls from the BIPMed public dataset. We could directly access genotypes of 17 candidate SNPs, available in the SNP array, and the remaining 31 SNPs were imputed using the BEAGLE v5.1 software. We performed an association test by logistic regression analysis, including the first five principal components as covariates. Furthermore, to expand the analysis of the candidate regions, we also interrogated 14,047 SNPs that flank the candidate SNPs (1 Mb). The statistical power was evaluated in terms of odds ratio and minor allele frequency (MAF) by the genpwr package. Differences in SNP frequencies between Brazilian and Europeans, sub-Saharan African, and Native Americans were evaluated by a two-proportion Z-test. We identified nine flanking SNPs, located on eight candidate regions, which presented association signals that passed the Bonferroni correction (rs12726617; rs9428842; rs1915992; rs1464634; rs6459526; rs2510087; rs9551042; rs9888879; and rs8133217;
    Language English
    Publishing date 2021-07-08
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606823-0
    ISSN 1664-8021
    ISSN 1664-8021
    DOI 10.3389/fgene.2021.672304
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  8. Article ; Online: Demographic history differences between Hispanics and Brazilians imprint haplotype features.

    da Cruz, Pedro Rodrigues Sousa / Ananina, Galina / Secolin, Rodrigo / Gil-da-Silva-Lopes, Vera Lúcia / Lima, Carmen Silvia Passos / de França, Paulo Henrique Condeixa / Donatti, Amanda / Lourenço, Gustavo Jacob / de Araujo, Tânia Kawasaki / Simioni, Milena / Lopes-Cendes, Iscia / Costa, Fernando Ferreira / de Melo, Mônica Barbosa

    G3 (Bethesda, Md.)

    2022  Volume 12, Issue 7

    Abstract: Admixture is known to greatly impact the genetic landscape of a population and, while genetic variation underlying human phenotypes has been shown to differ among populations, studies on admixed subjects are still scarce. Latin American populations are ... ...

    Abstract Admixture is known to greatly impact the genetic landscape of a population and, while genetic variation underlying human phenotypes has been shown to differ among populations, studies on admixed subjects are still scarce. Latin American populations are the result of complex demographic history, such as 2 or 3-way admixing events, bottlenecks and/or expansions, and adaptive events unique to the American continent. To explore the impact of these events on the genetic structure of Latino populations, we evaluated the following haplotype features: linkage disequilibrium, shared identity by descent segments, runs of homozygosity, and extended haplotype homozygosity (integrated haplotype score) in Latinos represented in the 1000 Genome Project along with array data from 171 Brazilians sampled in the South and Southeast regions of Brazil. We found that linkage disequilibrium decay relates to the amount of American and African ancestry. The extent of identity by descent sharing positively correlates with historical effective population sizes, which we found to be steady or growing, except for Puerto Ricans and Colombians. Long runs of homozygosity, a particular instance of autozygosity, was only enriched in Peruvians and Native Americans. We used simulations to account for random sampling and linkage disequilibrium to filter positive selection indexes and found 244 unique markers under selection, 26 of which are common to 2 or more populations. Some markers exhibiting positive selection signals had estimated time to the most recent common ancestor consistent with human adaptation to the American continent. In conclusion, Latino populations present highly divergent haplotype characteristics that impact genetic architecture and underlie complex phenotypes.
    MeSH term(s) Brazil ; Demography ; Genetics, Population ; Haplotypes ; Hispanic or Latino/genetics ; Humans ; Linkage Disequilibrium ; Polymorphism, Single Nucleotide
    Language English
    Publishing date 2022-05-04
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2629978-1
    ISSN 2160-1836 ; 2160-1836
    ISSN (online) 2160-1836
    ISSN 2160-1836
    DOI 10.1093/g3journal/jkac111
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  9. Article: Genetic variability in COVID-19-related genes in the Brazilian population.

    Secolin, Rodrigo / de Araujo, Tânia K / Gonsales, Marina C / Rocha, Cristiane S / Naslavsky, Michel / Marco, Luiz De / Bicalho, Maria A C / Vazquez, Vinicius L / Zatz, Mayana / Silva, Wilson A / Lopes-Cendes, Iscia

    Human genome variation

    2021  Volume 8, Page(s) 15

    Abstract: SARS-CoV-2 utilizes the angiotensin-converting enzyme 2 (ACE2) receptor and transmembrane serine protease (TMPRSS2) to infect human lung cells. Previous studies have suggested that different ... ...

    Abstract SARS-CoV-2 utilizes the angiotensin-converting enzyme 2 (ACE2) receptor and transmembrane serine protease (TMPRSS2) to infect human lung cells. Previous studies have suggested that different host
    Language English
    Publishing date 2021-04-02
    Publishing country England
    Document type Journal Article
    ISSN 2054-345X
    ISSN 2054-345X
    DOI 10.1038/s41439-021-00146-w
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  10. Article: Exploring a Region on Chromosome 8p23.1 Displaying Positive Selection Signals in Brazilian Admixed Populations: Additional Insights Into Predisposition to Obesity and Related Disorders.

    Secolin, Rodrigo / Gonsales, Marina C / Rocha, Cristiane S / Naslavsky, Michel / De Marco, Luiz / Bicalho, Maria A C / Vazquez, Vinicius L / Zatz, Mayana / Silva, Wilson A / Lopes-Cendes, Iscia

    Frontiers in genetics

    2021  Volume 12, Page(s) 636542

    Abstract: 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 ... ...

    Abstract 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 (
    Language English
    Publishing date 2021-03-25
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606823-0
    ISSN 1664-8021
    ISSN 1664-8021
    DOI 10.3389/fgene.2021.636542
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