Delta Variant of SARS-CoV-2 Replacement in Brazil: A National Epidemiologic Surveillance Program.

Coronavirus disease 2019 (COVID-19) pandemic has caused immeasurable impacts on the health and socioeconomic system. The real-time identification and characterization of new Variants of Concern (VOCs) are critical to comprehend its emergence and spread worldwide. In this sense, we carried out a national epidemiological surveillance program in Brazil from April to October 2021. Genotyping by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and sequencing were performed to monitor the dynamics and dissemination of VOCs in samples from 15 federative units. Delta VOC was first detected on June 2021 and took sixteen weeks to replace Gamma. To assess the transmissibility potential of Gamma and Delta VOCs, we studied the dynamics of RT-qPCR cycle threshold (Ct) score in the dominance period of each variant. The data suggest that Delta VOC has a higher transmission rate than Gamma VOC. We also compared relevant symptom patterns in individuals infected with both VOCs. The Delta-infected subjects were less likely to have low oxygen saturation or fatigue, altered results on chest computed tomography, and a propensity for altered X-rays. Altogether, we described the replacement of Gamma by Delta, Delta enhanced transmissibility, and differences in symptom presentation.

Epidemic Spread of SARS-CoV-2 Lineage B.1.1.7 in Brazil.

The emergence of diverse lineages harboring mutations with functional significance and potentially enhanced transmissibility imposes an increased difficulty on the containment of the SARS-CoV-2 pandemic [...].

Assessing false paternity risk in simulated motherless cases from more than 20 000 real exclusion trios.

BACKGROUND: When the mother's DNA profile is not available for paternity testing, there is a smaller probability that a locus will exclude an alleged father. This study aims to evaluate the risk of potential false paternity inclusions in motherless cases. STUDY DESIGN AND METHODS: More than 20 000 duos were generated by removing the maternal genotypes from exclusion trios. After recalculating paternity in these duos, any found inclusions would be false. RESULTS: The use of an appropriate number of loci, mutation model, and mutation rates to analyze motherless paternity cases was robust against false inclusions. A single potential false inclusion was observed in a case wherein kinship plays a role. This result highlights the importance of testing the mother when available and of obtaining information on family circumstances for the proper handling of cases involving related individuals. CONCLUSION: The guidelines we used here were sufficient to avoid false inclusions in a data set of more than 20 000 motherless cases.

Evolution and epidemic spread of SARS-CoV-2 in Brazil.

Brazil currently has one of the fastest-growing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemics in the world. Because of limited available data, assessments of the impact of nonpharmaceutical interventions (NPIs) on this virus spread remain challenging. Using a mobility-driven transmission model, we show that NPIs reduced the reproduction number from >3 to 1 to 1.6 in São Paulo and Rio de Janeiro. Sequencing of 427 new genomes and analysis of a geographically representative genomic dataset identified >100 international virus introductions in Brazil. We estimate that most (76%) of the Brazilian strains fell in three clades that were introduced from Europe between 22 February and 11 March 2020. During the early epidemic phase, we found that SARS-CoV-2 spread mostly locally and within state borders. After this period, despite sharp decreases in air travel, we estimated multiple exportations from large urban centers that coincided with a 25% increase in average traveled distances in national flights. This study sheds new light on the epidemic transmission and evolutionary trajectories of SARS-CoV-2 lineages in Brazil and provides evidence that current interventions remain insufficient to keep virus transmission under control in this country.

Fitting the Balding-Nichols model to forensic databases.

Large forensic databases provide an opportunity to compare observed empirical rates of genotype matching with those expected under forensic genetic models. A number of researchers have taken advantage of this opportunity to validate some forensic genetic approaches, particularly to ensure that estimated rates of genotype matching between unrelated individuals are indeed slight overestimates of those observed. However, these studies have also revealed systematic error trends in genotype probability estimates. In this analysis, we investigate these error trends and show how they result from inappropriate implementation of the Balding-Nichols model in the context of database-wide matching. Specifically, we show that in addition to accounting for increased allelic matching between individuals with recent shared ancestry, studies must account for relatively decreased allelic matching between individuals with more ancient shared ancestry.

New CODIS core loci allele frequencies for 96,400 Brazilian individuals.

We have reported the allele frequencies of 15 STR loci, including the original 13 CODIS core loci, in over 100,000 Brazilian individuals. A new CODIS core loci has been proposed, but the recently established Brazilian Integrated Network of DNA Databases made a decision in 2010 to postpone the implementation of this new set of loci due to the lack of allele frequency data for the Brazilian population. We aimed to report allele frequencies of 20 loci, estimated from 96,400 Brazilian individuals undergoing paternity testing during 2011-2013. The percentage of missing data was less than 0.6% for all loci, except for CSF1PO (3.15%) and D7S820 (2.5%). The dropout rates estimated by the MicroDrop software were 0.013 for CSF1PO, 0.000037 for D7S820 and less than 0.000001 for other loci. Small missing data percentages and dropout rates reflect the high quality of the data.

Association between methylation in mismatch repair genes, V600E BRAF mutation and microsatellite instability in colorectal cancer patients.

Colorectal cancer (CRC) corresponds to the third most prevalent type of cancer. Its origins can either be sporadic or inherited, being Lynch syndrome the most common form of hereditary CRC. The activation of BRAF oncogene, inactivation of mismatch repair genes by methylation of CpG islands, and microsatellite instability (MSI) have been reported to be involved in CRC development. The goal of the study was to characterize CRC tumors using clinical and molecular criteria through association and cluster analysis. Amsterdam II and Bethesda guidelines and molecular variables were analyzed in 77 patients from Brazil. The replication error (RER) status, based in microsatellite instability, showed association with metachronous tumor, MLH1 gene methylation and inverse association with left-sided and synchronous tumors. The PMS2 gene was considered the best predictor for differentiating levels of methylation and the mononucleotide were considered the best markers to evaluate RER status. The cluster 1 was characterized of individuals over 60 years of age, female, right-sided tumor, high microsatellite instability, and metachronous or synchronous tumors. The individuals in cluster 2 were younger than 45 years of age, male and showed left sided or rectum tumors, and microsatellite stability. Even though it was not observed a significant association, a higher number of individuals with family history of cancer and tumors without promoter methylation were found in cluster 2. The V600E mutation did not show association with clinical or molecular characteristics. Evaluation of MSI and methylation of MLH1 and PMS2 genes should be considered in order to assist with clinical diagnosis.

Assessment of microsatellite instability in colorectal cancer patients from Brazil.

UNLABELLED: The replication error status analysis of DNA, through microsatellite instability detection, has become an indispensable tool for hereditary non-polyposis colorectal cancer screening. This study investigated the microsatellite instability in Brazilian individuals presenting colorectal cancer. In this study, 66 patients were clinically analyzed according to Amsterdam II and Bethesda guidelines. Normal and tumour tissues were collected and analyzed for MSI degree according to molecular markers BAT25, BAT26, BAT40, APC-D5S346, D2S123, and D17S250. Eight patients (12.1%) fulfilled the Amsterdam II guidelines, and 15 (22.7%) met the Bethesda guidelines. BAT25 was the most sensitive marker (86.7%), while BAT26 was the least sensitive (66.7%). The specificity of both markers was 100%, but all of the markers must be used since the contribution of each marker to the sensitivity and specificity of the test is complementary. Proximal tumours were significantly predominant among RER+ patients. CONCLUSIONS: Patients with a family history of colorectal cancer with the tumour in the proximal colon must be screened to replication error status as early as possible in order to avoid the progression of the disease.

Mutações predisponentes à trombofilia em indivíduos de Minas Gerais - Brasil com suspeita clínica de trombose / Predisposing thrombophilic mutations in individuals with clinical suspicion of thrombosis from Minas Gerais, Brazil

A trombose é reconhecidamente uma doença de caráter multifatorial. Sua ocorrência está intimamente relacionada à presença de fatores genéticos e adquiridos que concorrem isoladamente ou em associação para o seu desencadeamento. No entanto, a frequência dos fatores genéticos pode variar de acordo com a origem étnica e com outros aspectos epidemiológicos dos grupos de indivíduos e populações estudadas. No Brasil, dados referentes a indivíduos brasileiros e em especial do estado de Minas Gerais são escassos. O objetivo do presente estudo foi investigar a frequência das mutações fator V Leiden e G20210A no gene protrombina em 1.103 indivíduos com suspeita clínica de trombofilia, empregando a técnica da reação em cadeia da polimerase seguida de restrição enzimática (PCR-RFLP). Os dados foram analisados usando-se o programa Epi Info versão 6.04. A amostra consistiu de 76,16 por cento mulheres e 23,84 por cento homens, com média de idade de 43,06± 14,65. A mutação fator V Leiden foi observada em heterozigose em 7,52 por cento dos indivíduos e em 0,36 por cento em homozigose. A mutação G20210A no gene da protrombina apresentou-se em heterozigose em 5,90 por cento dos indivíduos e em homozigose em 0,18 por cento. O presente trabalho mostra a importância dos testes genéticos conforme o perfil da população analisada, ressaltando informações epidemiológicas da população brasileira e benefícios clínicos.

Thrombosis is known to be a multifactorial disease. Its incidence is directly related to the presence of genetic and acquired factors that concur separately or in association to its appearance. However, the frequency of genetic factors can vary according to ethnic background and with other epidemiological aspects of populations. Data from Brazilian individuals and especially those from the State of Minas Gerais are scarce. The present study aims at investigating the frequencies of the factor v Leiden and the G20210G prothrombin gene mutations of 1103 individuals with clinical suspicion of thrombophilia employing the Polymerase Chain Reaction technique followed by enzymatic restriction (PCR-RFLP). The data were analyzed using the Epi Info computer program version 6.04. The sample constituted of 76.16 percent women and 23.84 percent men, with an average age of 43.06 ± 14.65 years. The factor V Leiden mutation was observed as heterozygosis in 7.5 percent of individuals and as homozygosis in 0.36 percent. The G20210A prothrombin gene mutation appeared as heterozygosis in 5.90 percent of the individuals and as homozygosis in 0.18 percent. The present study shows the importance of genetic tests taking into account the profile of the studied population, and stressing the epidemiological information of the Brazilian population and the clinical benefits.

Prevalence of C282Y and H63D mutations in the HFE gene of Brazilian individuals with clinical suspicion of hereditary hemochromatosis / Prevalência das mutações C282Y e H63D no gene HFE em indivíduos brasileiros com suspeita clínica de hemocromatose hereditária

Classical hereditary hemochromatosis is a recessive autosomal disease related to a systemic iron overload that is frequently related to C282Y and H63D mutations in the HFE gene. In Brazil, reports on HFE gene mutation frequencies are rare, mainly in regards to a representative sample population. This study intended to determine theprevalence of C282Y and H63D mutations among individuals with clinical suspicion of hereditary hemochromatosis. A total of 1955 patients were studied with C282Y andH63D mutations being detected by the polymerase chain reaction technique followed by enzymatic restriction. The sample consisted of 76.6% men and 23.4% women. The highest percentage of analyzed individuals (56.9%) was concentrated in the 41 to 60- year-old age group. Although there were no genic or genotypic differences between genders, a higher number of over 60-year-old women was observed. The C282Y mutation was found as homozygous in 2.9% of the cases and as heterozygous in 10.1%, while the H63D was homozygous in 4.3% and heterozygous in 30.6%. The C282Y and H63D mutant allele frequencies were 0.079 and 0.196, respectively. Thehighest frequency was observed for H63D which was in genetic equilibrium. This work is important to determine the genetic profile of the population with hereditary hemochromatosis in Brazi.

A hemocromatose hereditária clássica (HH) é uma doença autossômica recessiva caracterizada por uma sobrecarga sistêmica de ferro, a qual está freqüentemente relacionada às mutações C282Y e H63D no gene HFE. No Brasil, registros das freqüências das mutações no gene HFE são raros, principalmente envolvendo uma amostra representativa da população. Este estudo teve como objetivo a determinação da prevalência das mutações C282Y e H63D em indivíduos com suspeita clínica de HH. Para isto, foram estudados 1955 pacientes para os quais as mutações C282Y e H63Dforam pesquisadas pela técnica de Reação em Cadeia da Polimerase seguida de digestão enzimática. A amostra consistiu de 76,6% homens e 23,4% de mulheres. A maioria dos indivíduos analisados (56,9%) estava concentrada no grupo de 41 a 60 anos. Embora não tenham sido observadas diferenças gênicas e genotípicas entreos gêneros, foi observado um maior número de mulheres na faixa etária acima dos 60 anos A mutação C282Y estava presente em homozigose em 2,9% dos indivíduos e em heterozigose em 10,1%, enquanto H63D estava presente em homozigose em 4,3% e emheterozigose em 30,6% dos indivíduos estudados. As freqüências dos alelos mutantes C282Y e H63D foram de 0,079 e 0,196, respectivamente. Além de mais freqüente entre a população estudada, a mutação H63D mostrou equilíbrio genético, ao contrário da mutação C282Y. Este trabalho tem como importância a determinação do perfil genético da população acometida pela HH no Brasil.