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In mammalian females, X-chromosome inactivation (XCI) acts as a dosage compensation mechanism that equalizes X-linked genes expression between homo-and heterogametic sexes. However, approximately 12-23% of X-linked genes escape from XCI, being bi-allelic expressed. Herein, we report on genetic and functional data from an asymptomatic female of a Fragile X syndrome family, who harbors a large deletion on the X-chromosome. Array-CGH uncovered that the de novo, terminal, paternally originated 32 Mb deletion on Xq25-q28 spans 598 RefSeq genes, including escape and variable escape genes. Androgen receptor (AR) and retinitis pigmentosa 2 (RP2) methylation assays showed extreme skewed XCI ratios from both peripheral blood and buccal mucosa, silencing the abnormal X-chromosome. Surprisingly, transcriptome-wide analysis revealed that escape and variable escape genes spanning the deletion are mostly upregulated on the active X-chromosome, precluding major clinical/cognitive phenotypes in the female. Metaphase high count, hemizygosity concordance for microsatellite markers, and monoallelic expression of genes within the deletion suggest the absence of mosaicism in both blood and buccal mucosa. Taken together, our data suggest that an additional protective gene-by-gene mechanism occurs at the transcriptional level in the active X-chromosome to counterbalance detrimental phenotype effects of large Xq deletions.

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Since enzymes catalyze almost all chemical reactions that occur in living organisms, it is crucial that genes encoding such activities are correctly identified and functionally characterized. Several studies suggest that the fraction of enzymatic activities in which multiple events of independent origin have taken place during evolution is substantial. However, this topic is still poorly explored, and a comprehensive investigation of the occurrence, distribution, and implications of these events has not been done so far. Fundamental questions, such as how analogous enzymes originate, why so many events of independent origin have apparently occurred during evolution, and what are the reasons for the coexistence in the same organism of distinct enzymatic forms catalyzing the same reaction, remain unanswered. Also, several isofunctional enzymes are still not recognized as nonhomologous, even with substantial evidence indicating different evolutionary histories. In this work, we begin to investigate the biological significance of the cooccurrence of nonhomologous isofunctional enzymes in human metabolism, characterizing functional analogous enzymes identified in metabolic pathways annotated in the human genome. Our hypothesis is that the coexistence of multiple enzymatic forms might not be interpreted as functional redundancy. Instead, these enzymatic forms may be implicated in distinct (and probably relevant) biological roles.

Genetic studies can provide several important informations for sustainable fisheries management, mainly for the identification of different genetic stocks. In Brazil, genetic studies of the sea-bob shrimp, Xiphopenaeus kroyeri, produced important new information on the systematics of the genus, demonstrating the presence of anonymous cryptic species and outlining their geographical distribution and the levels of genetic diversity and population structuring of Brazilian species. Allozymes and sequence polymorphisms of the mitochondrial COI gene have also been used to beget diagnosis systems for the correct species identification. Recently, geometric morphometrics emerged as a powerful methodology for identifying operational taxonomic units, confirming genetic data with great similarity of results, and representing a promising tool to assist the identification of fishery stocks. Geometric morphometrics analyses were used to characterize Xiphopenaeus samples from Brazil, showing significant differences among populations, confirming previous patterns revealed by molecular data. This study gathers the information produced so far about the molecular systematics, patterns of geographic distribution of the cryptic Xiphopenaeus species, genetic and morphometric characterizations of variability and delineation of population boundaries. It intends to determine distribution and structuring consensus patterns of the genetic variability, aiming to support management and conservation actions as well as to identify gaps of knowledge and direct future efforts in order to address them.Keywords: Xiphopenaeus kroyeri; Xiphopenaeus riveti; cryptic species; molecular systematics; geometric morphometrics; fisheries genetics A CONTRIBUIÇÃO DA GENÉTICA NO ESTUDO DAS POPULAÇÕES DE CAMARÃO SETE-BARBAS DO LITORAL BRASILEIRO RESUMOEstudos genéticos podem fornecer diversas informações importantes para o manejo sustentável da pesca, tendo um relevante papel na identificação de estoques geneticamente distintos. No Brasil, estudos genéticos do camarão sete-barbas, Xiphopenaeus kroyeri, têm produzido novas e importantes informações sobre a sistemática do gênero, revelando espécies crípticas anônimas e delineando suas distribuições geográficas e os níveis de diversidade genética e estruturação populacional das espécies brasileiras. Alozimas e polimorfismos de sequência do gene mitocondrial COI também têm sido usados para gerar sistemas de diagnóstico para a identificação de espécies. Recentemente, a morfometria geométrica surgiu como uma metodologia poderosa para a identificação de unidades taxonômicas operacionais, confirmando os dados genéticos com grande similaridade de resultados, e representando uma ferramenta promissora para auxiliar na identificação dos estoques pesqueiros. Análises de morfometria geométrica foram utilizadas para caracterizar amostras de Xiphopenaeus do Brasil, mostrando diferenças significativas entre as populações, confirmando padrões anteriores revelados por dados moleculares. Este trabalho reúne as informações ...

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Background Multisystem Inflammatory Syndrome in Children (MIS-C) is a life-threatening complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which manifests as a hyper inflammatory process with multiorgan involvement in predominantly healthy children in the weeks following mild or asymptomatic coronavirus disease 2019 (COVID-19). However, host monogenic predisposing factors to MIS-C remain elusive. Methods Herein, we used whole exome sequencing (WES) on 16 MIS-C Brazilian patients to identify single nucleotide/InDels variants as predisposition factors associated with MIS-C. Results We identified ten very rare variants in eight genes (FREM1, MPO, POLG, C6, C9, ABCA4, ABCC6, and BSCL2) as the most promising candidates to be related to a higher risk of MIS-C development. These variants may propitiate a less effective immune response to infection or trigger the inflammatory response or yet a delayed hyperimmune response to SARS-CoV-2. Protein–Protein Interactions (PPIs) among the products of the mutated genes revealed an integrated network, enriched for immune and inflammatory response mechanisms with some of the direct partners representing gene products previously associated with MIS-C and Kawasaki disease (KD). In addition, the PPIs direct partners are also enriched for COVID-19-related gene sets. HLA alleles prediction from WES data allowed the identification of at least one risk allele in 100% of the MIS-C patients. Conclusions This study is the first to explore host MIS-C-associated variants in a Latin American admixed population. Besides expanding the spectrum of MIS-C-associated variants, our findings highlight the relevance of using WES for characterising the genetic interindividual variability associated with COVID-19 complications and ratify the presence of overlapping/convergent mechanisms among MIS-C, KD and COVID-19, crucial for future therapeutic management.