1,627 research outputs found

    Unraveling the genetic background of individuals with a clinical familial hypercholesterolemia phenotype

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    Familial hypercholesterolemia (FH) is a common genetic disorder of lipid metabolism caused by pathogenic/likely pathogenic variants in LDLR, APOB, and PCSK9 genes. Variants in FH-phenocopy genes (LDLRAP1, APOE, LIPA, ABCG5, and ABCG8), polygenic hypercholesterolemia, and hyperlipoprotein (a) [Lp(a)] can also mimic a clinical FH phenotype. We aim to present a new diagnostic tool to unravel the genetic background of clinical FH phenotype. Biochemical and genetic study was performed in 1,005 individuals with clinical diagnosis of FH, referred to the Portuguese FH Study. A next-generation sequencing panel, covering eight genes and eight SNPs to determine LDL-C polygenic risk score and LPA genetic score, was validated, and used in this study. FH was genetically confirmed in 417 index cases: 408 heterozygotes and 9 homozygotes. Cascade screening increased the identification to 1,000 FH individuals, including 11 homozygotes. FH-negative individuals (phenotype positive and genotype negative) have Lp(a) >50 mg/dl (30%), high polygenic risk score (16%), other monogenic lipid metabolism disorders (1%), and heterozygous pathogenic variants in FH-phenocopy genes (2%). Heterozygous variants of uncertain significance were identified in primary genes (12%) and phenocopy genes (7%). Overall, 42% of our cohort was genetically confirmed with FH. In the remaining individuals, other causes for high LDL-C were identified in 68%. Hyper-Lp(a) or polygenic hypercholesterolemia may be the cause of the clinical FH phenotype in almost half of FH-negative individuals. A small part has pathogenic variants in ABCG5/ABCG8 in heterozygosity that can cause hypercholesterolemia and should be further investigated. This extended next-generation sequencing panel identifies individuals with FH and FH-phenocopies, allowing to personalize each person’s treatment according to the affected pathway

    ABC AO TCC: PROCESSO DE ALFABETIZA√á√ÉO E SEUS IMPACTOS SOBRE UNIVERSIT√ĀRIOS ORIUNDOS DE ESCOLAS P√öBLICAS

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    This qualitative research aimed to understand if there are reading and writing difficulties in the academic environment on the part of students coming from public schools as a result of the literacy process in childhood. Research sample were 13 students from Cear√°‚Äôs Federal University/ Sobral Campus Psychology Undergraduate Program. Participant‚Äôs reports were collected and analyzed using semi-structured interviews technique and Thematic Analysis method. Research results point that academic language presented in the undergraduate program, as well as the basic schooling process, marked by a teaching gap, are factors related to reading and writing difficulties encountered by students in higher education. The research began after approval by the Research Ethics Committee (UEVA), attested by the Certificate for Presentation of Ethical Appreciation (CAAE) 40106320.4.0000.5053 and technical note 4.504,740.A presente pesquisa, de car√°ter qualitativo, buscou compreender se h√° dificuldades de leitura e escrita no meio acad√™mico por parte de estudantes provenientes de escolas p√ļblicas em decorr√™ncia do processo de alfabetiza√ß√£o na inf√Ęncia. Para isso, recortamos nossa amostra a 13 estudantes do curso de Psicologia da Universidade Federal do Cear√° ‚Äď Campus Sobral. Foram utilizadas entrevistas semiestruturadas como t√©cnica para coleta dos relatos dos participantes e o m√©todo da An√°lise Tem√°tica para a an√°lise dos mesmos. Como resultados, identificamos que a linguagem acad√™mica presente no curso, bem como o processo b√°sico de escolariza√ß√£o, marcado pela defasagem no ensino, s√£o fatores implicados nas dificuldades de leitura e escrita encontradas pelos discentes no ensino superior. A pesquisa teve in√≠cio ap√≥s aprova√ß√£o do Comit√™ de √Čtica em Pesquisa (UEVA), com Certificado para Apresenta√ß√£o de Aprecia√ß√£o √Čtica (CAAE) 40106320.4.0000.5053 e parecer 4.504.740

    Table3_Rescuing the Brazilian Agave breeding program: morphophysiological and molecular characterization of a new germplasm.xlsx

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    Agaves have been a valuable resource in dryland areas for centuries, providing fibers (sisal), food, and beverages. However, the advent of synthetic fibers has led to a decrease in research on Agave, resulting in the cessation of breeding programs in Brazil. With the rise of climate change, there is renewed interest in Agave for its potential as a biofuel feedstock in semiarid regions. Since 2016, we have been collecting Agave accessions throughout the country and retrieving what is left of Brazil‚Äôs original breeding program to establish a new germplasm bank. Here, we evaluated 21 of those accessions growing in the field. We used molecular markers and morphophysiological traits to characterize the plants. Based on the Mayahuelin molecular marker, we were able to reconstruct a phylogeny for the Brazilian accessions. The morphophysiological traits explained 34.6% of the phenotypic variation in the dataset, with physiological traits such as leaf water content, effective quantum efficiency of photosystem II (ő¶PSII), and specific leaf mass (SLM) as the most significant traits. Specifically, we evaluated nine Agave species and found that the physiological traits, rather than the morphological ones, were the most significant. Leaf water content was negatively correlated with specific leaf mass, which could be used as a marker for selecting cultivars with higher biomass accumulation. Interestingly, ő¶PSII and chlorophyll content were negatively correlated, suggesting photochemical adaptations throughout the rosette. Molecular and phenotypic data suggest that A. amaniensis, which is frequently considered a synonym of A. sisalana, is effectively another species. Overall, this study provides valuable information on the physiological traits of Brazilian Agave accessions and is a starting point for selecting more productive and climate-resilient cultivars for biorenewables production.</p