Trypanosoma cruzi infection induces DNA double-strand breaks and activates DNA damage response pathway in host epithelial cells.

Trypanosoma cruzi, the etiological agent of Chagas disease, invades many cell types affecting numerous host-signalling pathways. During the T. cruzi infection, we demonstrated modulations in the host RNA polymerase II activity with the downregulation of ribonucleoproteins affecting host transcription and splicing machinery. These alterations could be a result of the initial damage to the host DNA caused by the presence of the parasite, however, the mechanisms are not well understood. Herein, we examined whether infection by T. cruzi coincided with enhanced DNA damage in the host cell. We studied the engagement of the DNA damage response (DDR) pathways at the different time points (0-24 h post-infection, hpi) by T. cruzi in LLC-MK2 cells. In response to double-strand breaks (DSB), maximum phosphorylation of the histone variant H2AX is observed at 2hpi and promotes recruitment of the DDR p53-binding protein (53BP1). During T. cruzi infection, Ataxia-telangiectasia mutated protein (ATM) and DNA-PK protein kinases remained active in a time-dependent manner and played roles in regulating the host response to DSB. The host DNA lesions caused by the infection are likely orchestrated by the non-homologous end joining (NHEJ) pathway to maintain the host genome integrity.

Vegetable substrates as an alternative for the inclusion of lactic acid bacteria with probiotic potential in food matrices.

Vegetable substrates are food matrices with micronutrients, antioxidants, and fiber content with a high potential for bioprocesses development. In addition, they have been recognized as essential sources of a wide range of phytochemicals that, individually or in combination, can act as bioactive compounds with potential benefits to health due to their antioxidant and antimicrobial activity and recently due to their status as prebiotics in the balance of the human intestinal microbiota. This systematic review explores the benefits of lactic fermentation of plant matrices such as fruits, vegetables, legumes, and cereals by bacteria with probiotic potential, guaranteeing cell viability (106-107 CFU/mL) and generating bioactive metabolic products for modulation of the gut microbiome.

Identification of Biomarkers Related to the Efficacy of Radiotherapy in Pancreatic Cancer.

BACKGROUND/AIM: Pancreatic cancer (PC) has one of the highest mortality rates, with an overall five-year survival rate of only 7%. When diagnosed, PC is limited to the pancreas in only 20% of patients, whereas in 50% it has already metastasized. This is due to its late diagnosis, which makes the treatments used, such as radiotherapy, difficult, and reduces survival rates. Therefore, the importance of this study in detecting genes that may become possible biomarkers for this type of tumor, especially regarding the human secretome, is highlighted. These genes participate in pathways that are responsible for tumor migration and resistance to therapies, along with other important factors. MATERIALS AND METHODS: To achieve these goals, the following online tools and platforms have been expanded to discover and validate these biomarkers: The Human Protein Atlas database, the Xena Browser platform, Gene Expression Omnibus, the EnrichR platform and the Kaplan-Meier Plotter platform. RESULTS: Our study adopted a methodology that allows the identification of potential biomarkers related to the effectiveness of radiotherapy in PC. Inflammatory pathways were predominantly enriched, related to the regulation of biological processes, primarily in cytokine-derived proteins, which are responsible for tumor progression and other processes that contribute to the development of the disease. CONCLUSION: Radiotherapy treatment demonstrated greater efficacy when used in conjunction with other forms of therapy since it decreased the expression of essential genes involved in several inflammatory pathways linked to tumor progression.

Bio-yogurt with the inclusion of phytochemicals from carrots (Daucus carota): a strategy in the design of functional dairy beverage with probiotics.

The development of yogurt with functional characteristics from bioactive compounds such as fiber, antioxidants, and probiotics represents a novel strategy in designing value-added dairy beverages. However, biotechnological challenges are present in these bioprocesses, such as the selection of probiotic strains, as well as the correlation with the physicochemical characteristics of the fermentative metabolism of probiotic microorganisms. Therefore, yogurt could be a vehicle for including probiotic bacteria, bioactive compounds, and phytochemicals that allow synergistic effects in the development of bioprocesses with potential benefits for the host's health. Therefore, this article aims to review the current conditions of bio-yogurt production, discuss the physicochemical and bioactive composition (sugars, fiber, vitamins), and include phytochemicals from carrots to establish synergistic relationships with probiotic microorganisms to obtain a functional dairy beverage.

Navigating the boundaries between metabolism and epigenetics in trypanosomes.

Epigenetic marks enable cells to acquire new biological features that favor their adaptation to environmental changes. These marks are chemical modifications on chromatin-associated proteins and nucleic acids that lead to changes in the chromatin landscape and may eventually affect gene expression. The chemical tags of these epigenetic marks are comprised of intermediate cellular metabolites. The number of discovered associations between metabolism and epigenetics has increased, revealing how environment influences gene regulation and phenotype diversity. This connection is relevant to all organisms but underappreciated in digenetic parasites, which must adapt to different environments as they progress through their life cycles. This review speculates and proposes associations between epigenetics and metabolism in trypanosomes, which are protozoan parasites that cause human and livestock diseases.

Immunogenetics of HLA-B: SNP, allele, and haplotype diversity in populations from different continents and ancestry backgrounds.

HLA-B is among the most variable gene in the human genome. This gene encodes a key molecule for antigen presentation to CD8+ T lymphocytes and NK cell modulation. Despite the myriad of studies evaluating its coding region (with an emphasis on exons 2 and 3), few studies evaluated introns and regulatory sequences in real population samples. Thus, HLA-B variability is probably underestimated. We applied a bioinformatics pipeline tailored for HLA genes on 5347 samples from 80 different populations, which includes more than 1000 admixed Brazilians, to evaluate the HLA-B variability (SNPs, indels, MNPs, alleles, and haplotypes) in exons, introns, and regulatory regions. We observed 610 variable sites throughout HLA-B; the most frequent variants are shared worldwide. However, the haplotype distribution is geographically structured. We detected 920 full-length haplotypes (exons, introns, and untranslated regions) encoding 239 different protein sequences. HLA-B gene diversity is higher in admixed populations and Europeans while lower in African ancestry individuals. Each HLA-B allele group is associated with specific promoter sequences. This HLA-B variation resource may improve HLA imputation accuracy and disease-association studies and provide evolutionary insights regarding HLA-B genetic diversity in human populations.

Navigating the boundaries between metabolism and epigenetics in trypanosomes

Epigenetic marks enable cells to acquire new biological features that favor their adaptation to environmental changes. These marks are chemical modifications on chromatin-associated proteins and nucleic acids that lead to changes in the chromatin landscape and may eventually affect gene expression. The chemical tags of these epigenetic marks are comprised of intermediate cellular metabolites. The number of discovered associations between metabolism and epigenetics has increased, revealing how environment influences gene regulation and phenotype diversity. This connection is relevant to all organisms but underappreciated in digenetic parasites, which must adapt to different environments as they progress through their life cycles. This review speculates and proposes associations between epigenetics and metabolism in trypanosomes, which are protozoan parasites that cause human and livestock diseases.

Promoting adequate and healthy food in early childhood education: a systematic review / Promoção da alimentação adequada e saudável na educação infantil: uma revisão sistemática

Abstract Objectives: to identify and describe the characteristics of studies that address the promotion of adequate and healthy food in early childhood education units and their repercussions on the school community. Methods: the search and selection were performed according to the PRISMA recommendations in the Medline databases via OVID, EMBASE and LILACS. Data extraction took placeusing a table developed by the authors. The evaluation of the quality of the evidence of the studies was carried out through the risk of bias using an adapted scale. Result: twelve articles that met the eligibility criteria were selected. All studies were applied in public or private educational institutions with a median of 236 participants. In the analysis of food and nutrition education activities, the most adopted with preschoolers were playful; with the parents it was the meetings and counseling; and with the professionals it was the training. The methodological qualification of the studies was considered low, which may be related to their limitations included in this review, mainly due to the types of designs adopted, the time and lack of continuity of interventions and sample size. Conclusion: food and nutrition education activities seem to be a promising strategy in knowledge, adoption of healthy eating practices and transmission of values in the school community.

Resumo Objetivos: identificar e descrever as características de estudos que abordam a promoção da alimentação adequada e saudável em unidades de educação infantil e suas repercussões na comunidade escolar. Métodos: a busca e seleção foram realizadas segundo as recomendações do PRISMA nas bases de dados Medline via OVID, EMBASE e LILACS. A extração de dados ocorreu utilizando uma tabela elaborada pelas autoras. A avaliação da qualidade das evidências dos estudos foi realizada por meio do risco de viés utilizando uma escala adaptada. Resultados: foram selecionados 12 artigos que atenderam aos critérios de elegibilidade. Todos os estudos foram aplicados em instituições de ensino públicas ou privadas com uma mediana de 236 participantes. Na análise das atividades de educação alimentar e nutricional, as mais adotadas com os pré-escolares foram as lúdicas; com os pais foram as reuniões e aconselhamentos; e com os profissionais foram as capacitações. A qualificação metodológica dos estudos foi considerada baixa, podendo estar relacionada às limitações dos próprios estudos incluídos nesta revisão, principalmente pelos tipos de desenhos adotados, o tempo e a falta de continuidade das intervenções e tamanho amostrai. Conclusão: atividades de educação alimentar e nutricional parecem ser uma estratégia promissora na disseminação do conhecimento, adoção de práticas alimentares saudáveis e transmissão de valores na comunidade escolar.

Uso de belimumabe em paciente com lúpus eritematoso sistêmico refratário ao tratamento convencional: relato de caso / Use of belimumab in a patient with systemic lupus erythematosus refractory to conventional treatment: case report

O lúpus eritematoso sistêmico (LES) é uma doença de caráter imunomediado, ocasionada por fatores hormonais, ambientais e genéticos. Caracteriza-se pela presença de autoanticorpos reativos para diferentes células e tecidos, apresentando manifestações clínicas diversificadas, períodos de exacerbação e remissão, o que dificulta o tratamento desses pacientes. Este relato de caso destaca o progresso do uso de anticorpo monoclonal humano em uma paciente do gênero feminino, diagnosticada com LES em maio de 2019, aos 30 anos, e, por ser refratária ao tratamento medicamentoso convencional, utilizou o tratamento com anticorpo monoclonal humano belimumabe, com início em setembro de 2019. O belimumabe é um anticorpo monoclonal humano que se liga à proteína estimuladora de linfócito B (BLyS) solúvel, inclusive dos autorreativos, e desta maneira, reduz a diferenciação de linfócitos B em plasmócitos, diminuindo os níveis de IgG sérica e dos anticorpos anti-dsDNA, além de melhorar o quadro clínico dos pacientes. Apesar de ser um medicamento biológico de alto custo, diminui drasticamente os sintomas clínicos do LES, possibilitando a redução do uso do corticoide e os efeitos consequentes de seu uso, além de reestabelecer os parâmetros laboratoriais alterados pela doença, sem alteração de indicadores hepáticos e renais. O LES não tem cura, logo, o objetivo do tratamento é diminuir os sintomas e conter as fases ativas da doença.

Systemic lupus erythematosus is an immune-mediated disease caused by hormonal, environmental and genetic factors. It is characterized by the presence of reactive autoantibodies to different cells and tissues, with diverse clinical manifestations and periods of exacerbation and remission, which complicates treatment. This case report highlights progress with the use of a human monoclonal antibody in a woman diagnosed with systemic lupus erythematosus in May 2019 (at age 30). Since she was refractory to conventional drugs, belimumab treatment was begun in September 2019. Belimumab is a human monoclonal antibody that binds to soluble B lymphocyte-stimulating proteins, including self-reactive ones, and reduces the differentiation of B lymphocytes into plasma cells, decreasing the serum IgG and anti-dsDNA antibody levels, in addition to improving patient clinical status. Despite being a high-cost biological drug, it drastically reduces the clinical symptoms of systemic lupus erythematosus, enabling reduced used of corticosteroids and their effects, in addition to reestablishing laboratory parameters altered by the disease, without changing liver and kidney indicators. Since systemic lupus erythematosus has no cure, the goal of treatment is to reduce symptoms and the active phases of the disease.

MUC22, HLA-A, and HLA-DOB variants and COVID-19 in resilient super-agers from Brazil.

Background: Although aging correlates with a worse prognosis for Covid-19, super elderly still unvaccinated individuals presenting mild or no symptoms have been reported worldwide. Most of the reported genetic variants responsible for increased disease susceptibility are associated with immune response, involving type I IFN immunity and modulation; HLA cluster genes; inflammasome activation; genes of interleukins; and chemokines receptors. On the other hand, little is known about the resistance mechanisms against SARS-CoV-2 infection. Here, we addressed polymorphisms in the MHC region associated with Covid-19 outcome in super elderly resilient patients as compared to younger patients with a severe outcome. Methods: SARS-CoV-2 infection was confirmed by RT-PCR test. Aiming to identify candidate genes associated with host resistance, we investigated 87 individuals older than 90 years who recovered from Covid-19 with mild symptoms or who remained asymptomatic following positive test for SARS-CoV-2 as compared to 55 individuals younger than 60 years who had a severe disease or died due to Covid-19, as well as to the general elderly population from the same city. Whole-exome sequencing and an in-depth analysis of the MHC region was performed. All samples were collected in early 2020 and before the local vaccination programs started. Results: We found that the resilient super elderly group displayed a higher frequency of some missense variants in the MUC22 gene (a member of the mucins' family) as one of the strongest signals in the MHC region as compared to the severe Covid-19 group and the general elderly control population. For example, the missense variant rs62399430 at MUC22 is two times more frequent among the resilient super elderly (p = 0.00002, OR = 2.24). Conclusion: Since the pro-inflammatory basal state in the elderly may enhance the susceptibility to severe Covid-19, we hypothesized that MUC22 might play an important protective role against severe Covid-19, by reducing overactive immune responses in the senior population.

Factors associated with paid work after the dam failure: Brumadinho Health Project.

OBJECTIVE: To analyze the factors associated with paid work, after the dam failure, based on geographic strata, among men and women residing in Brumadinho, Minas Gerais. METHODS: Baseline data from participants of the Brumadinho Health Project, aged 18 years or older, obtained through a questionnaire, between July and November 2021 (n=2,783) were used. The dependent variable was paid work after the dam failure and the explanatory variables were geographic stratum, age, education, race/skin color, self-perception of health and employment relationship before the event. The adjusted analysis was estimated by logistic regression. All analyses were performed separately for men and women. RESULTS: Paid work after the dam failure was reported by 58.3% (95%CI 55.0-61.6) of the participants, with the highest prevalence among men (71.4%; 95%CI 67.1-75.3) compared to women (48.6%; 95%CI 44.3-52.8) (p<0.001). After adjustments, the results showed that the population who was directly exposed to the disaster was less likely to have a paid work after it, both for women (OR=0.68; 95%CI 0.48-0.95) and for men (OR=0.48; 95%CI 0.30-0.78). In addition, women directly exposed to the disaster and who reported being self-employed before it were less likely to have a paid work, compared to women who reported being employed with or without a formal contract. CONCLUSION: Participation in the labor market is determined by several factors. Thus, intersectoral policies are necessary the population's demands of life and work are met in disaster situations.

Effects of the Finishing Protocols and Oral Hygiene Procedures in the Microhardness and Surface Roughness of CAD/CAM Ceramics

ABSTRACT: The objective of this in vitro study was to evaluate the effects of finishing protocols and oral hygiene procedures on the surface and mechanical properties of CAD/CAM ceramics. Specimens (n = 96, (15x10x2mm) of the leucite glass-ceramic (LGC) and feldspathic ceramic (FP) received mechanical polishing or glazing. Surface roughness (Ra) and microhardness (VHN) were obtained with a profilometer and a hardness tester, respectively, before and after each oral hygiene procedure (TB: toothbrushing; PB: prophylaxis with paste and rubber cup; and BJ: prophylaxis with bicarbonate jet). ANOVA, paired t and Tukey's tests were applied (a=0.05). For both materials, only BJ affected Ra's values when mechanical polishing was performed. Moreover, no significant variations in VHN were observed only for LGC glazed with TB. Significant Ra and VHN changes in both materials were observed with BJ. Besides, BJ exhibited similar effects to TB on VHN, regardless of the material and finishing protocol used. Changes in mechanical and surface properties varied with the finishing protocol and the oral hygiene method. In general, prophylaxis with bicarbonate jet was the most harmful method for both materials and the type of finishing protocol did not have a protective effect against changes produced by oral hygiene methods.

RESUMEN: El objetivo de este estudio in vitro fue evaluar los efectos de los protocolos de acabado y los procedimientos de higiene oral sobre la superficie y las propiedades mecánicas de las cerámicas CAD/CAM. Los especímenes (n = 96, (15x10x2mm) de vitrocerámica de leucita (LGC) y cerámica feldespática (FP) recibieron pulido mecánico o glaseado. La rugosidad de la superficie (Ra) y la microdureza (VHN) se obtuvieron con un perfilómetro y un probador de dureza, respectivamente, antes y después de cada procedimiento de higiene oral (TB: cepillado dental; PB: profilaxis con pasta y vaso de hule; y BJ: profilaxis con chorro de bicarbonato). Se aplicaron ANOVA, t pareada y prueba de Tukey (a=0.05). Para ambos materiales, solo BJ afectó los valores de Ra cuando se realizó el pulido mecánico. Además, no se observaron variaciones significativas en VHN solo para LGC vidriado con TB. Se observaron cambios significativos de Ra y VHN en ambos materiales con BJ. Además, BJ exhibió efectos similares a TB en VHN, independientemente del material y protocolo de acabado utilizado Los cambios en las propiedades mecánicas y superficiales variaron con el protocolo de acabado y el método de higiene oral. En general, la profilaxis con chorro de bicarbonato fue el método más perjudicial, tanto los materiales como el tipo de protocolo de acabado no tuvieron un efecto protector frente a los cambios producidos por los métodos de higiene oral.

Helminth and ectoparasitic faunas of the Harris's hawk, Parabuteo unicinctus (Accipitriformes: Accipitridae), in Chile: new data on host-parasite associations for Neotropical raptors.

Birds of prey harbor a wide spectrum of various parasites, mostly with a heteroxenous life cycle. However, most reports on their parasites come from Europe. Although the Harris's hawk (Parabuteo unicinctus) is a widespread species in America, parasitological surveys on this hawk are mostly focused on coprological findings and ectoparasites, with poor attention paid to helminths. The aim of this study was to gather new and additional data on host-parasite associations for the Harris's hawk. Twenty-nine birds from central and southern Chile were necropsied. Further, nine birds from a rehabilitation center and 22 museum specimens were inspected for ectoparasites. Sixty-eight percent of birds hosted at least one parasite species. Four lice species, one mite species and eight helminth species (five nematodes, two platyhelminthes and one acanthocephalan) were recorded. Parasitic lice Colpocephalum nanum and Nosopon chanabense, and a nematode Cyathostoma (Hovorkonema) americana were recorded for the first time in raptors from the Neotropics. A feather mite, Pseudalloptinus sp., nematodes, Physaloptera alata and Microtetrameres sp., and a trematode Neodiplostomim travassosi, were recorded for the first time in Chile. The presence of diverse heteroxenous helminths reported here in the Harris's hawk could be explained by the generalist diet of this raptor.

Probiotics in anthocyanin-rich fruit beverages: research and development for novel synbiotic products.

Anthocyanin-rich fruit beverages are of special interest as functional products due to their antioxidant activity, antimicrobial properties against pathogens, and, more recently, evidence of prebiotic potential. The stability and bioactivity of anthocyanins, probiotics, prebiotics, and synbiotics have been extensively documented in beverage models and reviewed separately. This review summarizes the most recent works and methodologies used for the development of probiotic and synbiotic beverages based on anthocyanin-rich fruits with a synergistic perspective. Emphasis is made on key optimization factors and strategies that have allowed probiotic cultures to reach the minimum recommended doses to obtain health benefits at the end of the shelf life. The development of these beverages is limited by the high acidity and high content of phenolic compounds in anthocyanin-rich fruits. However, a proper selection of probiotic strains and strategies for their media adaptation may improve their viability in the beverages. Fermentation increases the viability of the probiotic cultures, improves the safety and stability of the product, and may increase its antioxidant capacity. Moreover, fermentation metabolites may synergistically enhance probiotic health benefits. On the other hand, the inoculation of probiotics without fermentation allows for synbiotic beverages with milder changes in terms of physicochemical and sensory attributes.

Filamentous fungi from textile effluent and their potential application for bioremediation process.

The inappropriate disposal of toxic compounds generated by industrial activity has considerably impacted the environment. Microbial communities inhabiting contaminated sites may represent ecological alternatives for the decontamination of environments. The present work aimed to search the potential of fungi isolated from wastewater treatment plant of a textile industry for bioremediation processes. Twenty-three fungi previously isolated from textile effluent were evaluated for their abilities to degrade pollutants using heavy metal and hydrocarbon tolerance assays. One isolate was subjected to pyrene degradation due its ability to tolerate hydrocarbon. The majority of isolates were resistant to at least two metals tested, i.e. chrome, copper, lead and aluminum. Isolates Penicillium sp. ITF 2, Penicillium rubens ITF 4, Penicillium sp. ITF 12 and ITF 20 (not identified) showed tolerance to tested heavy metals in all concentrations. ITF 12 and ITF 20 were able to tolerate benzene, toluene and hexane, separately. ITF 12 was able to degrade 24.9% of pyrene after 5 days of cultivation. The results encourage future studies to optimize the tolerance and degradation assay using the isolates that showed the best results, as well as studies on the treatment of environments contaminated with heavy metals and hydrocarbons, including industrial textile effluents.

Filamentous fungi from textile effluent and their potential application for bioremediation process.

The inappropriate disposal of toxic compounds generated by industrial activity has considerably impacted the environment. Microbial communities inhabiting contaminated sites may represent ecological alternatives for the decontamination of environments. The present work aimed to search the potential of fungi isolated from wastewater treatment plant of a textile industry for bioremediation processes. Twenty-three fungi previously isolated from textile effluent were evaluated for their abilities to degrade pollutants using heavy metal and hydrocarbon tolerance assays. One isolate was subjected to pyrene degradation due its ability to tolerate hydrocarbon. The majority of isolates were resistant to at least two metals tested, i.e. chrome, copper, lead and aluminum. Isolates Penicillium sp. ITF 2, Penicillium rubens ITF 4, Penicillium sp. ITF 12 and ITF 20 (not identified) showed tolerance to tested heavy metals in all concentrations. ITF 12 and ITF 20 were able to tolerate benzene, toluene and hexane, separately. ITF 12 was able to degrade 24.9% of pyrene after 5 days of cultivation. The results encourage future studies to optimize the tolerance and degradation assay using the isolates that showed the best results, as well as studies on the treatment of environments contaminated with heavy metals and hydrocarbons, including industrial textile effluents.

Feasibility indicators of telemedicine for patients with dementia in a public hospital in Northeast Brazil during the COVID-19 pandemic.

BACKGROUND: The use of telemedicine has become a fundamental tool in healthcare in recent years, especially at times of Covid-19 pandemic. Currently, there are several telemedicine tools that are simple, inexpensive, and effective means of communication. This article aims to describe indicators of feasibility including patient recruitment, attendance, discomfort (internet connection issues and/or noncompliant patient behavior), satisfaction, and travel time and cost savings of virtual telemedicine consultations for patients with dementia. METHODS: The study was conducted at the Geriatrics Department of Hospital Universitário Walter Cantídio (HUWC) in Fortaleza, Brazil, between May 1st and December 31, 2020. The eligibility criteria included previous diagnosis of dementia syndrome and receiving care at the hospital's dementia outpatient clinic in face-to-face consultations in the preceding 12 months. Patients were excluded if they did not feel comfortable with virtual consultations, did not have the required communication technology available or their caregiver was not available to attend the remote consultation. The patients were recruited from the outpatient dementia clinic's medical appointment scheduling list. The intervention was designed as a one-time consultation and it included treatment approaches and health promotion recommendations. RESULTS: Patient recruitment, attendance and discomfort rates were 85.5%, 97.7% and 9.4%, respectively. To attend face-to-face visits, they reported an average travel time (including the consultation) of 233.21 minutes and average total cost of 60.61 reais (around USD 11). The study intervention was well accepted among the patients and their caregivers with 97.6% being satisfied. Many were happy to avoid long waits in crowded medical waiting rooms and the risk of covid-19 contagion. CONCLUSIONS: We found good recruitment, attendance, and acceptance rates of remote care for the follow-up of dementia patients as well as low discomfort rates. TRIAL REGISTRATION: Brazilian Trial Registry (REBEC) RBR-9xs978.

Whole-genome sequencing of 1,171 elderly admixed individuals from São Paulo, Brazil.

As whole-genome sequencing (WGS) becomes the gold standard tool for studying population genomics and medical applications, data on diverse non-European and admixed individuals are still scarce. Here, we present a high-coverage WGS dataset of 1,171 highly admixed elderly Brazilians from a census-based cohort, providing over 76 million variants, of which ~2 million are absent from large public databases. WGS enables identification of ~2,000 previously undescribed mobile element insertions without previous description, nearly 5 Mb of genomic segments absent from the human genome reference, and over 140 alleles from HLA genes absent from public resources. We reclassify and curate pathogenicity assertions for nearly four hundred variants in genes associated with dominantly-inherited Mendelian disorders and calculate the incidence for selected recessive disorders, demonstrating the clinical usefulness of the present study. Finally, we observe that whole-genome and HLA imputation could be significantly improved compared to available datasets since rare variation represents the largest proportion of input from WGS. These results demonstrate that even smaller sample sizes of underrepresented populations bring relevant data for genomic studies, especially when exploring analyses allowed only by WGS.