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Ligula intestinalis is a cestode parasite that affects freshwater fish in different countries of the world. The current study aims to reveal the phylogenetic, genetic and haplotype diversity of mt-CO1 gene sequences sent to the NCBI database from different countries by using in-silico analysis. The 105 mt-CO1 (371 bp) gene sequences of L. intestinalis obtained from NCBI were used for bioinformatics analyses. Sequences were subjected to phylogenetic and haplotype analysis. As a result of the haplotype analysis of L. intestinalis, 38 haplotypes were obtained from 13 different countries. Hap24 constituted 44.76% of the obtained haplotype network. Changes in nucleotides between haplotypes occurred at 1-84 different points. China and Turkey have highest fixation index (Fst) values of 0.59761, while the lowest (-0.10526) was found between Russia and Turkey. This study provides a baseline for future studies on extensive scale on the epidemiology, ecological aspects, distribution pattern, transmission dynamics and population dispersion of L. intestinalis worldwide. Resumo Ligula intestinalis é um parasita cestódeo que acomete peixes de água doce em diversos países do mundo. O presente estudo visa revelar a diversidade filogenética, genética e de haplótipos das sequências do gene mt-CO1 enviadas ao banco de dados do NCBI de diferentes países, por meio de análise in-silico. As sequências gênicas de 105 mt-CO1 (371 pb) de L. intestinalis obtidas do NCBI foram utilizadas para análises bioinformáticas. As sequências foram submetidas a análise filogenética e de haplótipos. Como resultado da análise de haplótipos de L. intestinalis, 38 haplótipos foram obtidos de 13 países diferentes. Hap24 constituiu 44,76% da rede de haplótipos obtida. Mudanças nos nucleotídeos entre os haplótipos ocorreram em 1-84 pontos diferentes. A China e a Turquia apresentam os maiores valores do índice de fixação (Fst), 0,59761, enquanto o menor (-0,10526) foi encontrado entre a Rússia e a Turquia. Este estudo fornece uma linha de base para futuros estudos em larga escala sobre epidemiologia, aspectos ecológicos, padrão de distribuição, dinâmica de transmissão e dispersão populacional de L. intestinalis em todo o mundo.

This study, about RPW and date palms, is under the scope of date palm bioecology and nutrition (nutritional ecology) which includes the integration of several areas of research such as date palm biochemistry, genetics, and RPW infestation behavior through various date palm cultivars. Date palm (Phoenix dactylifera L.; Arecaceae) production is under threat from the red palm weevil (RPW), Rhynchophorus ferrugineus Oliver. A better understanding of genetic diversity within date palm cultivars can be useful for its implementation within the insect IPM program in the future. Three indices, namely simple-sequence repeats (SSR) markers to elucidate genetic diversity, chemical components, and a natural infestation index of RPW, were used to evaluate the resistant or susceptible date palm cultivars in Qassim. Based on a field survey of RPW infestation within 79 date palm farms involving 11 cultivars at Qassim, the sensitivity and resistance cultivars were determined. The resistant date palm cultivars were Nabtat Ali, Shakrah, red Sukary, and um Kobar which had the lowest degree of RPW abundance %. Values of the essential minerals, nitrogen, phosphorus, potassium, and calcium within the date palm cultivars were also estimated. RPW abundance % was negatively correlated with the calcium content of date palm cultivars. The principal component analysis (PCA) revealed that the calcium content and RPW abundance % were highly affected by the cultivars. SSR markers of the date palm cluster tree divided genotypes into two main groups at similarity coefficients between 0.56 and 0.91. The 1st group included; Nabtet Ali, Red Sukary, Um Kobar, and Shakrah with similarity coefficients between 0.56, this group was the most resistant cultivars. Therefore, SSR markers were able to characterize and resolve genetic diversity in date palm cultivars for RPW resistance. When SSR markers coupled with higher calcium (Ca) content can efficiently replace indices in characterizing resistant date-palm genotypes with a high confidence level. Integration between date palm genetic diversity, chemical structures, and RPW infestations rates promoted the understanding of the interplay between the diversity of RPW management (short-time scale), and the resistance genes, plant nutrition, and dynamics of the diversity of RPW through domestication and diversification (long-timescale). Therefore, our results may lead to a change in RPW control strategies by switching to using safe alternative pesticide control methods (Resistant cultivars of date palm), which are underestimated and may reveal the impact of low-cost, but highly effective agricultural practices in the field of date production in the world. Understanding the genetic structure and calcium content of date palm cultivars mechanisms could help to predict date palm resistance against RPW populations in the new IPM strategy in RPW control. Resumo Este estudo, sobre RPW e tamareiras, está no âmbito da bioecologia e nutrição da tamareira (ecologia nutricional) que inclui a integração de várias áreas de pesquisa, como bioquímica da tamareira, genética e comportamento de infestação de RPW através de vários cultivares de tamareira. A produção da tamareira (Phoenix dactylifera L.; Arecaceae) está ameaçada pelo gorgulho vermelho da palmeira (RPW), Rhynchophorus ferrugineus Oliver. A compreensão mais aprofundada da diversidade genética dentro dos cultivares de tamareiras pode ser útil para sua implementação no futuro programa de MIP de insetos. Três índices, ou seja, marcadores de sequência simples (SSR) para elucidar a diversidade genética, componentes químicos e um índice de infestação natural de RPW, foram utilizados para avaliar as cultivares de tamareiras resistentes ou suscetíveis em Qassim. Com base em uma pesquisa de campo da infestação de RPW em 79 fazendas de tamareiras envolvendo 11 cultivares em Qassim, as cultivares de sensibilidade e resistência foram determinadas. As cultivares de tamareiras resistentes foram Nabtat Ali, Shakrah, red Sukary e um Kobar, que apresentaram o menor grau de abundância de RPW. Também foram estimados os valores dos minerais essenciais, nitrogênio, fósforo, potássio e cálcio nas cultivares de tamareira. A porcentagem de abundância de RPW correlacionou-se negativamente com o teor de cálcio das cultivares de tamareira. A análise de componentes principais (PCA) revelou que o teor de cálcio e a abundância de RPW % foram altamente afetados pelas cultivares. Marcadores SSR da tamareira dividiram os genótipos em dois grupos principais com coeficientes de similaridade entre 0,56 e 0,91. O 1º grupo incluiu; Nabtet Ali, Red Sukary, Um Kobar e Shakrah com coeficientes de similaridade entre 0,56, este grupo foi o de cultivares mais resistentes. Portanto, os marcadores SSR foram capazes de caracterizar e resolver a diversidade genética em cultivares de tamareiras para resistência a RPW. Quando os marcadores SSR associados ao maior teor de cálcio (Ca) podem substituir com eficiência os índices na caracterização de genótipos de tamareiras resistentes com alto nível de confiança. A integração entre diversidade genética da tamareira, estruturas químicas e taxas de infestação de RPW promoveu a compreensão da interação entre a diversidade de manejo de RPW (escala de tempo curto) e os genes de resistência, nutrição de plantas e dinâmica da diversidade de RPW por meio da domesticação e diversificação (longo prazo). Portanto, nossos resultados podem levar a uma mudança nas estratégias de controle de RPW, passando a usar métodos alternativos seguros de controle de pesticidas (cultivares resistentes de tamareira), sendo subestimados e podem revelar o impacto de práticas agrícolas de baixo custo, mas altamente eficazes no campo de produção de tâmaras no mundo. Compreender a estrutura genética e o teor de cálcio dos mecanismos dos cultivares de tamareira pode ajudar a prever a resistência da tamareira contra populações de RPW na nova estratégia de IPM no controle de RPW.

Copy number variations (CNV) are an important source of genetic variation. CNV has been increasingly studied and frequently associated with diseases and productive traits in livestock animals. However, CNV-based genome-wide association studies (GWAS) in Santa Inês sheep, one of the principal sheep breeds in Brazil, have not yet been reported. Thus, the aim of this study was to investigate the association between CNV and growth, efficiency and carcass traits in sheep. The Illumina OvineSNP50 BeadChip array was used to detect CNV in 491 Santa Inês individuals. Then, CNV-based GWAS was performed with a linear mixed model approach considering a genomic relationship matrix, for ten traits: (1) growth: body weight at three (W3) and six (W6) months of age; (2) efficiency: residual feed intake (RFI) and feed efficiency (FE) and (3) carcass: external carcass length (ECL), leg length (LL), carcass yield (CY), commercial cuts weight (CCW), loin eye area (LEA) and subcutaneous fat thickness (SFT). We identified 1,167 autosomal CNV in 438 sheep, with 294 non-redundant CNV, ranging from 21.8 to 861.9 kb, merged into 216 distinct copy number variation regions (CNVRs). One significant CNV segment (p

Glycoproteomics is a powerful yet analytically challenging research tool. Software packages aiding the interpretation of complex glycopeptide tandem mass spectra have appeared, but their relative performance remains untested. Conducted through the HUPO Human Glycoproteomics Initiative, this community study, comprising both developers and users of glycoproteomics software, evaluates solutions for system-wide glycopeptide analysis. The same mass spectrometrybased glycoproteomics datasets from human serum were shared with participants and the relative team performance for N - and O-glycopeptide data analysis was comprehensively established by orthogonal performance tests. Although the results were variable, several high-performance glycoproteomics informatics strategies were identified. Deep analysis of the data revealed key performance-associated search parameters and led to recommendations for improved ‘high-coverage’ and ‘high-accuracy’ glycoproteomics search solutions. This study concludes that diverse software packages for comprehensive glycopeptide data analysis exist, points to several high-performance search strategies and specifies key variables that will guide future software developments and assist informatics decision-making in glycoproteomics., This analysis presents the results of a community-based evaluation of existing software for large-scale glycopeptide data analysis.

Objective: To analyze potential influences of the R/X genetic polymorphism of the ACTN3 gene, as well as of anthropometric and metabolic characteristics on the functional performance of elderly women assisted in primary health care. Method: One hundred and forty-one elderly women were assessed in terms of anthropometric, metabolic and functional aspects, in addition to clinical, cognitive and demographic characteristics. Allele and genotype frequencies of ACTN3 gene polymorphism were determined. Results: 141 elderly women (68.30 ± 6.18 years) were evaluated. No significant differences (p > 0.05) were observed between the RR and RX/XX genotypes in the elderly women’s functional performance, anthropometric or metabolic characteristics. The TUG test completion time showed positive correlations with age, body mass index, waist circumference, and fat percentage (s = 0.315; p < 0.001; s = 0.238; p = 0.005; s = 0.174; p = 0.039; s = 0.207; p = 0.014), respectively. Negative correlations were found between the TUG test with absolute handgrip strength (s = - 0.314; p < 0.001) and relative handgrip strength (s = - 0.380; p < 0.001). Conclusion: In our study, there were no influences from ACTN3 gene polymorphisms on the functional performance of the elderly women, which is influenced by other factors. RESUMO Objetivo: analisar as potenciais influências do polimorfismo genético R/X do gene ACTN3 e das características antropométricas e metabólicas no desempenho funcional de mulheres idosas atendidas na atenção primária em saúde. Método: Cento e quarenta e uma idosas foram avaliadas em relação as características antropométricas, metabólicas, funcionais, aspectos clínicos, cognitivos e demográficos. Foram determinadas as frequências de alelos e genótipos do polimorfismo do gene ACTN3. Resultados: 141 idosas (68,30 ± 6,18 anos) foram avaliadas. Não foram observadas diferenças significativas (p > 0,05) entre os genótipos RR e RX/XX no desempenho funcional, características antropométricas ou metabólicas das idosas. O tempo de realização do TUG apresentou correlações positivas com idade, índice de massa corporal, circunferência da cintura e percentual de gordura (s = 0,315; p < 0,001; s = 0,238; p = 0,005; s = 0,174; p = 0,039; s = 0,207; p = 0,014) respectivamente. Correlações negativas foram observadas entre o TUG com força de preensão manual absoluta (s = - 0,314; p < 0,001) e relativa (s = - 0,380; p < 0,001). Conclusão: Em nosso estudo, não foram observadas influências dos polimorfismos do gene ACTN3 no desempenho funcional das idosas, sendo este, influenciado por outros fatores.

Formas atípicas da Esclerose Lateral Amiotrófica (ELA) representam apresentações clínicas com evolução, história natural, achados laboratoriais e neurofisiológicos pouco habituais em relação às formas típicas do adulto. A ELA juvenil representa forma bastante rara, pouco reconhecida em nosso meio, caracterizada por sintomas e sinais motores iniciados antes dos 25 anos de idade, com base monogênica definida em 40% dos casos. O perfil clínico e genético associado à ELA juvenil é desconhecido no cenário brasileiro. Objetivos: Caracterização dos aspectos clínicos e genéticos relacionados a pacientes brasileiros com ELA juvenil e análise de novas correlações clínico-genéticas em casos de início juvenil de ELA. Métodos: Foi realizado estudo clínico retrospectivo pela análise de registros médicos de 1350 pacientes acompanhados em um centro de referência em Doença do Neurônio Motor/ELA, entre janeiro de 2001 e dezembro de 2020. Foram considerados critérios de inclusão: (i) pacientes com formas provável ou definitiva da ELA em forma típica ou atípica, segundo critérios de El Escorial revisado e de Awaji-Shima; (ii) sinais e sintomas motores iniciados antes dos 25 anos de idade; (iii) exclusão de outros diagnósticos diferenciais; (iv) não preencher critérios de exclusão; e (v) estar de acordo com o Termo de Consentimento Livre e Esclarecido ou de Assentimento. Foram critérios de exclusão: (i) sintomas e sinais motores iniciados após os 25 anos; (ii) indivíduos assintomáticos, com alteração genética isolada relacionada à ELA; (iii) critério diagnóstico ELA possível de acordo com critérios neurofisiológicos de El Escorial revisado e de Awaji- Shima; (iv) diagnóstico de outra forma de Doença do Neurônio Motor; e (v) ausência de consentimento ou assentimento. Foram revisados aspectos clínicos, laboratoriais, neurofisiológicos, radiológicos, pontuações nas escalas de estadiamento de King’s College e Milano-Torino e na ALS Functional Rating Scale-Revised (ALSFRS-R), perfil cognitivo captado pelo teste cognitivo e comportamental ECAS, bem como análise de variantes genéticas observadas em painéis genéticos de sequenciamento de próxima geração ou no sequenciamento completo do exoma. Resultados: Total de 61 pacientes preencheram critérios de inclusão para ELA juvenil, sendo 31 pacientes do sexo feminino. A idade média ao início dos sintomas foi de foi de 16,6 (±7,7) anos e ao diagnóstico de 26,3 (±12,1) anos. Um total de 72% dos casos de ELA juvenil apresentava início espinal e dez pacientes foram a óbito no período do estudo. Contexto definidor de ELA familiar foi observado em 40,9% dos pacientes e consanguinidade familiar em 31,1% dos casos. Foram observadas as seguintes associações com formas monogênicas de ELA: SPG11 (n=12), ALS2 (n=7), SOD1 (n=5), FUS (n=3), ZFYVE26 (n=3), VAPB (n=3), SPAST (n=2), KIF5A (n=2), PRKRA (n=2), SPTLC1 (n=1), SORL1 (n=1), WASHC5 (n=1), BSCL2 (n=1), GARS (n=1), SETX (n=1), ERCC2 (n=1), MAPT (n=1) e PLA2G6 (n=1). Dois casos se relacionaram a dupla associação genética: SPG11 com TBK1; e SPAST com SPG7. A base genética monogênica permaneceu indeterminada em 19,7% dos casos. Menores pontuações iniciais no ALSFRS-R foram vistas nas formas associadas aos genes SOD1, ALS2, PRKRA e FUS. Taxas de queda anual do ALSFRS-R superiores à média foram vistas nas formas FUS e ALS2, e inferiores nas formas KIF5A, SPG11 e PRKRA. As menores pontuações médias do ECAS foram vistas nos casos associados aos genes FUS e SPG11 e as maiores ao gene SPAST. Leucoencefalopatia, atrofia cortical e de corpo caloso foram as alterações mais comumente observadas nos estudos radiológicos. Conclusões: O perfil clínico e genético da ELA juvenil é bastante complexo e heterogêneo no Brasil, sendo preponderantes as formas ligadas aos genes SPG11, ALS2 e SOD1. Novas associações genéticas puderam ser estabelecidas a partir deste estudo, mostrando importante sobreposição genética com as paraparesias espásticas hereditárias, neuropatias hereditárias e outras condições neurodegenerativas. Disfunção cognitiva é achado frequente e pouco reconhecido na ELA juvenil. Atypical forms of Amyotrophic Lateral Sclerosis (ALS) represent unusual clinical presentation with distinct clinical course, natural history, laboratory and neurophysiological findings in relation to typical adult-onset ALS. Juvenile ALS represents an extremely rare and underrecognized condition with motor symptoms and signs starting before age 25 years and showing a definite monogenic basis in 40% of cases. Clinical and genetic profile associated with juvenile ALS is unknown in Brazil. Objectives: Characterization of clinical and genetic aspects of Brazilian patients with juvenile ALS and establishment of new genetic correlations. Methods: A retrospective clinical study was performed with the analysis of medical records from 1350 patients followed-up in a specialized center in Motor Neuron Disease/ALS, in the period between January 2001 and December 2020. Inclusion criteria: (i) patients with typical or atypical ALS forms with probable or definitive diagnosis of ALS, regarding the revised El Escorial and Awaji-Shima criteria; (ii) onset of motor symptoms before age 25 years; (iii) exclusion of other differential diagnosis; (iv) patients do not fulfill exclusion criteria; and (v) agreement with the informed consent form. Exclusion criteria: (i) onset of motor symptoms after age 25 years; (ii) asymptomatic individuals, with isolated abnormal genetic findings related to ALS; (iii) patients with possible diagnosis of ALS according to El Escorial and Awaji-Shima criteria; (iv) confirmed diagnosis of other Motor Neuron Disease; and (v) disagreement with the informed consent form. Clinical, laboratory, neurophysiological and neuroimaging aspects, individual performance in King’s College and Milano-Torino staging scale and in ALS Functional Rating Scale-Revised, cognitive and behavioral profile in ECAS scale, and analysis of genetic variants obtained in next- generation sequencing or Whole-exome sequencing tests were all evaluated. Results: 61 patients with juvenile ALS fulfilled inclusion criteria (31 female patients). Mean age at motor symptom-onset was 16,6 (±7,7) years and at diagnosis of 26,3 (±12,1) years. A total of 72% of cases presented with spinal-onset ALS and ten patients died during the study period. Familial ALS was observed in 40,9% of cases and familial consanguinity was present in 31,1% of cases. Genetically-defined juvenile ALS cases included: SPG11 (n=12), ALS2 (n=7), SOD1 (n=5), FUS (n=3), ZFYVE26 (n=3), VAPB (n=3), SPAST (n=2), KIF5A (n=2), PRKRA (n=2), SPTLC1 (n=1), SORL1 (n=1), WASHC5 (n=1), BSCL2 (n=1), GARS (n=1), SETX (n=1), ERCC2 (n=1), MAPT (n=1) and PLA2G6 (n=1). Two cases presented with double genetic association: SPG11 with TBK1; and SPAST with SPG7. Undetermined monogenic basis was observed in 19,7% of cases. Lower initial scores in ALSFRS-R has been observed in patients with juvenile ALS associated with SOD1, ALS2, PRKRA and FUS genes. Higher year decrease taxes of ALSFRS-R were seen in FUS and ALS2 gene cases, and lower taxes in KIF5A, SPG11 and PRKRA gene forms. The lower mean values in ECAS score has been observed in FUS and SPG11 gene subtypes and the higher mean values with SPAST gene variants. Leukoencephalopathy, cortical atrophy, and thin corpus callosum were the most common abnormal radiological findings observed. Conclusion: Clinical and genetic profile of juvenile ALS is complex and heterogeneous in Brazil, with the main presentations associated with SPG11, ALS2 and SOD1 genes. New genetic associations could be established with this study, disclosing the importance of genetic overlap with Hereditary spastic paraplegia, Inherited neuropathies, and other neurodegenerative disorders. Cognitive dysfunction is a common and underrecognized complication of juvenile ALS.

Purpose To identify novel genes associated with intellectual disability (ID) in four unrelated families. Methods Here, through exome sequencing and international collaboration, we report eight individuals from four unrelated families of diverse geographic origin with biallelic loss-of-function variants in UBE4A. Results Eight evaluated individuals presented with syndromic intellectual disability and global developmental delay. Other clinical features included hypotonia, short stature, seizures, and behavior disorder. Characteristic features were appreciated in some individuals but not all; in some cases, features became more apparent with age. We demonstrated that UBE4A loss-of-function variants reduced RNA expression and protein levels in clinical samples. Mice generated to mimic patient-specific Ube4a loss-of-function variant exhibited muscular and neurological/behavioral abnormalities, some of which are suggestive of the clinical abnormalities seen in the affected individuals. Conclusion These data indicate that biallelic loss-of-function variants in UBE4A cause a novel intellectual disability syndrome, suggesting that UBE4A enzyme activity is required for normal development and neurological function.

SARS-CoV-2 virus emerged in December 2019 and has rapidly spread around the world. In January 2020, the first genome sequence was available, with approximately 30000 bases. Since then, the virus accumulated diverse mutations, leading to the emergence of different lineages. In this work, a review was carried out on the gold standard method for SARS-CoV-2 detection, addressing the factors that may contribute to the achievement of false negative or false positive results. An in-silico analysis identified the formation of primer and/or probe homodimers in the China CDC (ORF1ab target), Charité (E gene) and HKU (N gene) diagnostic kits; and heterodimers in the China CDC (N gene), Charité (E gene), and US CDC (N2 and N3 genes) kits, these being the kits more likely to generate false results. In this work, 34 genomes of SARS-CoV-2 were sequenced, from samples obtained between July/20 and July/21 in Ceará. These sequences, analyzed together with sequences deposited in the GISAID database in this period for Ceará, revealed the occurrence of 8 lineages between March and December 2020. The most prevalent strain was B.1.1.33 (n=45), followed by B.1 (n=21), B.1.212 (n=19) and P.2 (n=14). In this work, 202 SNVs (Single Nucleotide Variant) were identified among the 34 sequenced genomes. Mutations with >40% prevalence include p.F924F and p. P4715, both in ORF1ab; p.D614G in the S gene; p.I33T in ORF6; p.R203K, p.R203R, p.G204R and p.I292T in the N gene. The only mutation detected in 100% of our sequenced genomes was D614G in the S gene. Genomic surveillance of circulating lineages allows us to monitor the pandemic, assisting in government decision-making and in monitoring the virus. In GISAID database, few SARS-CoV-2 genomes come from samples collected in the first months of the pandemic in Ceará. Our data aim to fill these gaps and contribute to a better understanding of SARS-CoV-2 variants genetic diversity and their prevalence in Ceará.state. O vírus SARS-CoV-2 foi identificado em dezembro de 2019 e se espalhou rapidamente pelo mundo. Em janeiro de 2020, o primeiro genoma estava disponível, com aproximadamente 30000 bases. Desde então, o vírus acumulou diversas mutações, levando ao surgimento de diferentes linhagens. Neste trabalho, foi realizada uma revisão sobre o método padrão ouro para a detecção do SARS-CoV-2, abordando diversos fatores que podem contribuir para a obtenção de resultados falsos negativos ou falsos positivos. Uma análise in silico identificou a formação de homodímeros de iniciadores e/ou sondas nos kits de diagnóstico China CDC (ORF1ab target), Charité (gene E) e HKU (gene N); e heterodímeros nos kits China CDC (gene N), Charité (gene E), e US CDC (genes N2 e N3), sendo esses os kits mais passíveis de gerarem resultados falsos. Neste trabalho, também foi realizado o sequenciamento de 34 genomas do SARS-CoV-2, isolados entre julho/20 e julho/21 no Ceará. Essas sequencias, analisadas em conjunto com sequencias depositadas no banco de dados GISAID neste período para o Ceará, revelaram a ocorrência de 8 linhagens entre março e dezembro de 2020. A linhagem mais prevalente foi a B.1.1.33 (n=45), seguida por B.1 (n=21), B.1.212 (n=19) e P.2 (n=14). Além da identificação das linhagens circulantes, esse trabalho proporcionou a identificação de 202 SNVs (Variantes de Nucleotídeo Único), entre os 34 genomas sequenciados. Mutações com >40% de prevalência incluem p.F924F e p. P4715, ambos em ORF1ab; p.D614G no gene S; p.I33T em ORF6; p.R203K, p.R203R, p.G204R e p.I292T no gene N. A única mutação detectada em todos os 34 genomas sequenciados foi a D614G no gene S. A vigilância genômica das linhagens circulantes nos permite monitorar a pandemia, auxiliando na tomada de decisões do governo e no rastreamento do vírus. No banco de dados GISAID, poucos genomas de SARS-CoV-2 são provenientes de amostras coletadas nos primeiros meses da pandemia no Ceará. Nossos dados visam preencher essas lacunas e contribuir para o melhor entendimento da diversidade genética das variantes e sua prevalência no estado do Ceará.

CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior The inclusion of human diversity in genetic studies contributes not only to a better understanding of our history but also to solving biomedical issues such as disease susceptibility, response to medical treatments and elucidation of complex traits. Geneticists have known for more than a decade that focusing on people of European ancestry exacerbates health disparities, and genetic advances can not be applied to those who need it most. Thus, this thesis presents works that contribute to changing this scenario, seeking to increase the visibility of the genetic richness that exists beyond populations of European ancestry. Here, I present research findings that include admixed and non-admixed populations with diverse ancestries, from South American natives to Africans and Asians. The first chapter is a mini-review of the history of humanity on the American continent, told by the genetics of modern and ancient populations, from the arrival of the first humans to the process of admixture, where we also present complementary discussions about the updates of the discoveries made since the publication of this article in 2020. In chapter 2, we present an article published by my group that solves important questions in the Andean and Amazon genetic history, through methods of population genetics. In chapter 3, I devote myself to the methods of scanning these adaptive signatures and create a multi-methodological pipeline for the study of natural selection to minimize the chance of obtaining false positives. Chapter 4 is an important addition to genetically neglected populations and would be a complementary part of our chapter 1, where we applied advances with polygenic risk scores to admixed populations such as the Brazilian. Exploring the diversity of human genetics is not only important for neglected populations, but it is also essential to increase the capacity to make new discoveries. Thus, in the attachments, we present five articles exemplifying how the genomic mosaic of non-European populations is a rich source of information from different perspectives, including medical, historical and evolutionary aspects. The work presented here shows in different ways how the effort to generate data from underrepresented populations makes important contributions to science. A inclusão da diversidade humana nos estudos genéticos contribui não apenas para a melhor compreensão da nossa história, mas tambem para resolver questões biomédicas, como suscetibilidade a doenças, resposta a tratamentos médicos e elucidação de fenótipos complexos. Geneticistas sabem há mais de uma década, que o foco em pessoas de ancestralidade europeia agrava as disparidades de acesso a saúde por parte das populações globais, e os avanços genéticos não são levados a quem mais precisa. Assim, esta tese apresenta trabalhos que contribuem para mudar esse cenário, buscando aumentar a visibilidade da riqueza genética que existe além das populações de ancestralidade europeia. Aqui, apresento resultados de pesquisas que incluem populações miscigenadas e não-miscigenadas com ancestralidades diversas, desde nativos sulamericanos, até africanos e asiáticos. O primeiro capítulo é uma mini revisão da história da humanidade no continente americano, contada pela genética de populações atuais e antigas, desde a chegada dos primeiros seres humanos até o processo de miscigenação, onde tambem apresento discussões complementares sobre às atualizações das descobertas feitas desde a publicação desse artigo em 2020. No capitulo 2, apresento um artigo publicado pelo meu grupo que resolve questões importantes da história genética andina e amazônica, por meio de métodos de genética de populações. No capitulo 3 me aprofundo nos métodos de varredura dessas assinaturas adaptativas e crio um pipeline de estudo de seleção natural multi-metodológico para diminuir ao maximo a chance de se obter falsos-positivos. O Capitulo 4 é uma adição importante para às populações geneticamente negligenciadas e seria uma parte complementar ao nosso capitulo 1, onde eu aplico os avanços com scores poligenicos de riscos às populaçoes miscigenadas, como a Brasileira. Explorar a diversidade da genética humana não é importante apenas para as populações negligenciadas, mas também é essencial para aumentar a capacidade de fazer novas descobertas. Assim, apresento nos anexos, cinco artigos exemplificando como o mosaico genômico de populações não europeias é uma rica fonte de informações de diferentes perspectivas, incluindo aspectos médicos, históricos e evolutivos. O trabalho aqui apresentado mostra de diversas formas como o esforço de geração de dados a partir de populações sub-representadas traz importantes contribuições para a ciência.

he aims of this study were to investigate the genetic variability and the genotype × environment interaction for quality and yield traits in common bean (Phaseolus vulgaris L.), to evaluate the degree of informativeness of the evaluations of grain quality in only one environment, to estimate genetic parameters for grain quality traits, and to select lines with superior grain quality. We evaluated 81 carioca common bean lines in preliminary line trials in several environments for nutritional, technological, and commercial quality and selected the 20 superior lines, which were evaluated in validation trials in nine environments. Individual and combined ANOVAs were performed for all the traits. Correlations were estimated between Fe and Zn concentrations and yield; adaptability and phenotypic stability were analyzed; and superior genotypes were selected based on the Mulamba & Mock index. It is possible to increase the Fe, Zn, and crude protein concentrations and reduce cooking time; however, increasing crude fiber is a challenge. Preliminary evaluation of the quality traits in only one environment was effective and sufficient for selection of genotypes superior in Fe concentration, crude fiber, crude protein, and cooking time; and genetic gains can be obtained from selection for these traits. Genetic and phenotypic correlations were observed between Fe and Zn concentrations. The lines CNFC 16627, CNFC 16518, CNFC 16602, CNFC 16615, and CNFC 16520 are superior based on the selection index and are recommended for breeding for grain quality in carioca common bean. Made available in DSpace on 2021-09-10T15:05:59Z (GMT). No. of bitstreams: 1 cs.pdf: 249903 bytes, checksum: ef9f181f778db91831b3f000202db229 (MD5) Previous issue date: 2021

INTRODUCTION: The treatment of human and animal sporotrichosis is often performed with antifungal agents; however, the emergence of antifungal-resistant strains of Sporothrix species has been reported. We aimed to discuss the ability of Sporothrix species in developing resistance to the conventional antifungals and mechanisms for this. METHODOLOGY: Published data on databases (PubMed, Science Direct, Google Scholar) were investigated using a combination of keywords from 2008 to 2019 by the StArt tool. RESULTS: The minimal inhibitory concentrations values based on the Clinical and Laboratory Standards Institute (CLSI) from eight references were classified according to the epidemiological cutoff values in wild-type or non-wild-type strains. In this way, non-wild-type S. schenckii and, mainly, S. brasiliensis isolates were recognized on itraconazole, amphotericin B, terbinafine, and voriconazole, which are strains that deserve more attention toward antifungal control, with a probable risk of mutation to antifungal resistance. Among the few reviewed studied on antifungal resistance, the melanin production capacity (DHN-melanin, L-DOPA melanin, and pyomelanin), the low genetic diversity due to the abnormal number of chromosomes, and the mutation in cytochrome P450 are some of the factors for developing resistance mechanism. CONCLUSIONS: The emergence of Sporothrix species with in vitro antifungal resistance was evidenced and the possible mechanisms for resistance development may be due to the melanin production capacity, genetic diversity and mutations in cytochrome P450. Further studies should be carried out targeting gene expression for the development of antifungal resistance on Sporothrix species in order to prospect new therapeutic targets for human and veterinary use.

Size grading is a common management practice in fish farming to minimize growth variability. Such practice has not been established for pirarucu Arapaima gigas. Therefore, the present study assessed the effect of size grading on the growth of pirarucu. Juvenile pirarucu were divided into three groups: ungraded fish (U: mean initial weight 1.12 kg), small fish (S: mean initial weight 0.81 kg), and large fish (L: mean initial weight 1.36 kg), and reared for 129 days (phase I) and 158 additional days (phase II), consecutively. No significant difference was observed in the final length, specific growth rate, biomass, survival and feed conversion rate between fish groups. Ungraded fish presented a greater decrease in the coefficient of variation for weight in phase I than in phase II. Size sorting resulted in significantly higher growth after 287 days of farming in the L-graded fish (9.49 kg, final weight), followed by the ungraded group (8.80 kg) and S-graded group (8.01 kg). However, the mean weight of pooled S- and L-graded fish was similar to the ungraded fish group in phase I and phase II, indicating that grading did not improve the general performance of pirarucu in captivity. Made available in DSpace on 2020-03-17T00:37:39Z (GMT). No. of bitstreams: 1 CNPASA2020lajar.pdf: 787820 bytes, checksum: b928c656748c056eddc119958a51f226 (MD5) Previous issue date: 2020

Submitted by José Carlos de Oliveira Junior (j.oliveira-junior@unesp.br) on 2022-04-04T20:51:54Z No. of bitstreams: 1 Dissertação José Carlos - E. urophylla.pdf: 1955749 bytes, checksum: 9adcb06fd910d021f0d9044b8e66179f (MD5) Approved for entry into archive by Joao Josue Barbosa (joao.barbosa@unesp.br) on 2022-04-05T18:23:43Z (GMT) No. of bitstreams: 1 oliveira_junior_jc_me_ilha.pdf: 1954267 bytes, checksum: d0422a3bc2c1e6596d27c8574bfe4340 (MD5) Made available in DSpace on 2022-04-05T18:23:43Z (GMT). No. of bitstreams: 1 oliveira_junior_jc_me_ilha.pdf: 1954267 bytes, checksum: d0422a3bc2c1e6596d27c8574bfe4340 (MD5) Previous issue date: 2022-02-22 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Grande produtor de eucalipto, o estado do Mato Grosso do Sul tem uma base genética restrita ao clone AEC 144, o que implica na busca de genótipos adequados à região. Para tanto, o melhoramento sob diferentes estratégias de seleção tem papel fundamental na escolha dos materiais, mas demandam recursos e tempo. Por isso, uma alternativa a fim de diminuir o tempo é imprescindível, como a seleção precoce, associada às ferramentas moleculares, para avaliar a melhor recombinação entre genitores e estimar parâmetros mais criteriosos, importantes para a formação de pomares de sementes por mudas (PSM) e fornecer matéria prima de qualidade para a produção de celulose e madeira para serraria. O objetivo desta dissertação foi de verificar a variação genética em um teste de progênies de segunda geração de Eucalyptus urophylla (TP2G-TP-EU), tanto para características de crescimento como diâmetro a altura do peito, (DAP) e altura, quanto para o módulo de elasticidade, pensando na qualidade da madeira para serraria. Além disso, também foram avaliados os ganhos esperados e a diversidade genética com diferentes estratégias de seleção, e a correlação genética entre DAP e altura para a seleção precoce, com o intuito de formar um PSM de segunda geração, ao indicar as melhores recombinações por DAP entre os genitores selecionados. O TP2G-TP-EU foi instalado em 2016 em Selvíria-MS, oriundo de um PSM com 298 progênies. Seu delineamento experimental é em blocos casualizados, com 23 progênies, 30 repetições, com uma planta por parcela, em espaçamento 3 x 1,5 m. A altura (m) e o DAP (cm) foram mensurados entre 2017 e 2021, e o módulo de elasticidade (MOEd), coletado somente em 2021, usando o Treesonic, aparelho capaz de medir o MOEd da madeira em pé. As estimativas dos componentes de variância e parâmetros genéticos foram obtidas por REML/BLUP. A partir do valor aditivo individual, foram estimados os ganhos genéticos esperados para cada estratégia de seleção (S1 - individual; S2 - entre e dentro de progênies e S3 - dentro). Houve diferença significativa quanto ao LRT para os caracteres avaliados. O maior ganho genético esperado, para o DAP, ocorreu na S1 (6,68%). Houve alta correlação entre altura e DAP, seja em idades iguais ou diferentes. A correlação da posição dos indivíduos ao longo dos cinco anos do TP foi moderada a elevada (> 59%), com destaque entre o quarto e o quinto ano (97%), indicativo de potencial para a prática de seleção precoce para o estabelecimento de um PSM de segunda geração. Os 10 melhores cruzamentos foram selecionados para clonagem, por possuírem DAP com 75% de produtividade a mais do que a média, com 17,7 cm superiores à média geral (de 22,83 cm). A diferença entre as estratégias foi alta, sem comprometer a perda de alelos conforme o avanço dos ciclos de seleção. Para o modelo de elasticidade da madeira, as herdabilidades individuais foram médias, indicando potencial para o melhoramento dessa variável. Concluindo, a seleção individual é uma boa estratégia a ser aplicada nesta população apresentando maiores ganhos genéticos esperados, dando avanços nos siclos de melhoramento. Eucalyptus major producer, Mato Grosso do Sul state has a restricted genetic base to AEC 144 clone, which implies suitable genotypes search to the region. Therefore, breeding under different selection strategies plays a fundamental role in materials' choice, and require resources and time. Thus, an alternative to reduce time is essential, such as early selection, associated with molecular tools, to evaluate the best recombination between parents and estimate more careful parameters, important for seedlings seed orchards (SSO) formation and provide quality raw material for pulp and wood for sawmills production. The aim of this dissertation was to verify genetic variation in an Eucalyptus urophylla second-generation progenies of Eucalyptus urophylla test (TP2G-TP-EU), for growth characteristics as diameter at breast height (DBH) and height, as for elasticity modulus, considering wood quality for sawmills. Furthermore, the expected gains and genetic diversity with different selection strategies were also evaluated, and also the genetic correlation between DBH and height for early selection, in order to form a second-generation SSO, by indicating best DBH recombinations between selected parents. TP2G-TP-EU was installed in 2016 at Selvíria-MS, from a SSO with 298 progenies. Its experimental design is in randomized blocks, with 23 progenies, 30 replications, one plant per plot, spaced 3 x 1.5 m. Height (m) and DBH (cm) were measured between 2017 and 2021, and elasticity modulus (MOEd) was collected only in 2021, with Treesonic, device capable of measuring standing wood MOEd. Variance components and genetic parameters estimates were obtained by REML/BLUP. Based on individual additive value, expected genetic gains for each selection strategy were estimated (S1 - individual; S2 - between and within progenies and S3 - within). There was a significant difference regarding LRT for the evaluated characters. The highest expected genetic gain for DAP occurred in S1 (6.68%). There was a high correlation between height and DBH, whether at the same or different ages. Individuals' position correlation over PT five years was moderate to high (> 59%), with emphasis between the fourth and fifth year (97%), indicative of potential for early selection practice for a second-generation SSO establishment. 10 best crosses were selected for cloning, as they had DBH with 75% more productivity than average, with 17.7 cm higher than general average (22.83 cm). Difference between strategies was high, without compromising alleles loss as the selection cycles advanced. For wood elasticity model, individual heritabilities were average, indicating potential for this character improvement. In conclusion, individual selection is a good strategy to be applied in this population, presenting greater expected genetic gains, giving advances in breeding cycles. FAPESP: 2020/02059-6

Whole-genome sequence analyses have significantly contributed to the understanding of virulence and evolution of the Mycobacterium tuberculosis complex (MTBC), the causative pathogens of tuberculosis. Most MTBC evolutionary studies are focused on single nucleotide polymorphisms and deletions, but rare studies have evaluated gene content, whereas none has comprehensively evaluated pseudogenes. Accordingly, we describe an extensive study focused on quantifying and predicting possible functions of MTBC and Mycobacterium canettii pseudogenes. Using NCBI’s PGAP-detected pseudogenes, we analysed 25 837 pseudogenes from 158 MTBC and M. canetii strains and combined transcriptomics and proteomics of M. tuberculosis H37Rv to gain insights about pseudogenes' expression. Our results indicate significant variability concerning rate and conservancy of in silico predicted pseudogenes among different ecotypes and lineages of tuberculous mycobacteria and pseudogenization of important virulence factors and genes of the metabolism and antimicrobial resistance/tolerance. We show that in silico predicted pseudogenes contribute considerably to MTBC genetic diversity at the population level. Moreover, the transcription machinery of M. tuberculosis can fully transcribe most pseudogenes, indicating intact promoters and recent pseudogene evolutionary emergence. Proteomics of M. tuberculosis and close evaluation of mutational lesions driving pseudogenization suggest that few in silico predicted pseudogenes are likely capable of neofunctionalization, nonsense mutation reversal, or phase variation, contradicting the classical definition of pseudogenes. Such findings indicate that genome annotation should be accompanied by proteomics and protein function assays to improve its accuracy. While indels and insertion sequences are the main drivers of the observed mutational lesions in these species, population bottlenecks and genetic drift are likely the evolutionary processes acting on pseudogenes' emergence over time. Our findings unveil a new perspective on MTBC’s evolution and genetic diversity.

BACKGROUND Erythema nodosum leprosum (ENL) is an acute and systemic inflammatory reaction of leprosy characterised by painful nodules and involvement of various organs. Thalidomide is an immunomodulatory and anti-inflammatory drug currently used to treat this condition. Cereblon (CRBN) protein is the primary target of thalidomide, and it has been pointed out as necessary for the efficacy of this drug in others therapeutics settings. OBJECTIVES In this study, we aimed to evaluate the influence of CRBN gene variants on the dose of thalidomide as well as its adverse effects during treatment of ENL. METHODS A total of 103 ENL patients in treatment with thalidomide were included in this study. DNA samples were obtained from saliva and molecular analysis of CRBN gene were performed to investigate the variants rs1620675, rs1672770 and rs4183. Different genotypes of CRBN variants were evaluated in relation to their influence on the dose of thalidomide and on the occurrence of adverse effects. FINDINGS No association was found between CRBN variants and thalidomide dose variation. However, the genotypes of rs1672770 showed association with gastrointestinal effects (p = 0.040). Moreover, the haplotype DEL/C/T (rs4183/rs1672770/rs1620675) was also associated with gastrointestinal adverse effects (p = 0.015). MAIN CONCLUSIONS Our results show that CRBN variants affect the treatment of ENH with thalidomide, especially on the adverse effects related to the drug.

Genealogical data comprised 45,711 animals born between 1901 and 2016, with 48,127 animals in the pedigree file. Population structure was analyzed in terms of pedigree completeness, individual inbreeding coefficient (F), generation interval (L), rate of inbreeding (ΔF), effective population size (Ne), effective number of founders (ff), and effective number of ancestors (fa). The herd initially consisted of 13 bulls and 14 cows, and there were variations in the number of selected bulls and cows throughout the analyzed period, with 2,575 bulls, 13,691 cows, and 45,711 births recorded at the end of 2016. In total, 48.81% of the cows had only one progeny. Most dams (47.59%) were between three and seven years old, with a mean L in the population of 7.9 years. According to the results, 52.75% of the cows, 44.92% of the bulls, and 63.71% of the calves of the Guzerat breed in the northern region of Brazil showed some degree of inbreeding, with small-magnitude coefficients (0.56, 0.83, and 0.71% for cows, bulls, and calves, respectively). This fluctuation did not hinder the genetic evolution of the herd in the region. The effective population size does not seem to compromise the maintenance of genetic variability in the breed.

This study aimed to analyze the genetic variability of Coffea canephora population with 190 genotypes from cultivar ?ES8152?, based on morphoagronomic characteristics and vegetation index, to identify the most important characteristics for genetic divergence and compare them with commercial clones. The experiment was installed, in 2019, at the Bananal do Norte Experimental Farm/INCAPER, Cachoeiro de Itapemirim, ES, Brazil. The experiment was carried out in Federer?s augmented block design with three blocks, four common treatments (commercial clones A1, LB1, V8 and V12) and 190 regular treatments, genotypes from the seed production field of the conilon coffee cultivar ?ES8152?. At 24 months of age 14 morphoagronomic characteristics and vegetation index were evaluated. Descriptive analysis of the data, the estimation of the Standardized Euclidean Distance (ED) followed by the grouping by the methods of Tocher, UPGMA and principal coordinates, in addition to the relative importance of the characters estimated by the Singh methodology were performed. The most distant genotypes were 62 and 83 (ED=2.620) and the closest were 42 and 160 (ED=0.208). Genotype 83 stood out as the most distant among the others. The optimization and hierarchical groupings allowed the identification of genotypes 15, 81, 107 and 184 as similar to commercial clones. The discard analysis of variables recommended the elimination of the vegetation index and average internode length of the next diversity analysis. Principal coordinate analysis found phenotypic similarity of the genotypes 30, 81, 115, 141 and 163 with the clone V12, of the genotype 119 with the clone A1 and genotype 17 with clone LB1. The study, of morphoagronomic characters, allowed to detection the genetic diversity existing in the materials evaluated, indicating those with phenotypic similarity with the commercial clones, being possible the early identification of promising genotypes, agronomically superior, to start a breeding program for clonal selection, recurrent selection and controlled crosses to maximize heterosis. Made available in DSpace on 2022-08-25T13:20:45Z (GMT). No. of bitstreams: 1 Genetic-variability-of-conilon-coffee-population-from-cultivar.pdf: 1369713 bytes, checksum: d7b694376348a17e814b8f5f6eaab3ae (MD5) Previous issue date: 2022

Introduction: Although potential relationships with genetic variants of MLCK2, AMPD1 and COL5A1 have been detected in molecular studies evaluating sports performance from the genetic perspective, there are limited data in terms of muscle endurance and physical fitness. Materials and Methods: This study aimed to evaluate these variants in terms of lower limb muscle endurance and physical fitness in thirty-three soccer players. Genotypes were determined by High Resolution Melting (HRM) analysis in qPCR after genomic DNA was isolated from buccal swab samples from the participants. Measurements of lower limb muscle endurance, the dynamic leap and balance test (DLBT), and the standing broad jump test (SBJ) were taken for all the participants. Results: Greater height (p = 0.006), higher DLBT (p = 0.016) and SBJ (p = 0.033) scores, as well as greater left hip adduction (p

Oligogenic inheritance of autism spectrum disorder (ASD) has been supported by several studies. However, little is known about how the risk variants interact and converge on causative neurobiological pathways. We identified in an ASD proband deleterious compound heterozygous missense variants in the Reelin (RELN) gene, and a de novo splicing variant in the Cav3.2 calcium channel (CACNA1H) gene. Here, by using iPSC-derived neural progenitor cells (NPCs) and a heterologous expression system, we show that the variant in Cav3.2 leads to increased calcium influx into cells, which overactivates mTORC1 pathway and, consequently, further exacerbates the impairment of Reelin signaling. Also, we show that Cav3.2/mTORC1 overactivation induces proliferation of NPCs and that both mutant Cav3.2 and Reelin cause abnormal migration of these cells. Finally, analysis of the sequencing data from two ASD cohorts—a Brazilian cohort of 861 samples, 291 with ASD; the MSSNG cohort of 11,181 samples, 5,102 with ASD—revealed that the co-occurrence of risk variants in both alleles of Reelin pathway genes and in one allele of calcium channel genes confer significant liability for ASD. Our results support the notion that genes with co-occurring deleterious variants tend to have interconnected pathways underlying oligogenic forms of ASD.