When humans moved from Asia toward the Americas over 18,000 y ago and eventually peopled the New World they encountered a new environment with extreme climate conditions and distinct dietary ...resources. These environmental and dietary pressures may have led to instances of genetic adaptation with the potential to influence the phenotypic variation in extant Native American populations. An example of such an event is the evolution of the fatty acid desaturases (FADS) genes, which have been claimed to harbor signals of positive selection in Inuit populations due to adaptation to the cold Greenland Arctic climate and to a protein-rich diet. Because there was evidence of intercontinental variation in this genetic region, with indications of positive selection for its variants, we decided to compare the Inuit findings with other Native American data. Here, we use several lines of evidence to show that the signal of FADS-positive selection is not restricted to the Arctic but instead is broadly observed throughout the Americas. The shared signature of selection among populations living in such a diverse range of environments is likely due to a single and strong instance of local adaptation that took place in the common ancestral population before their entrance into the New World. These first Americans peopled the whole continent and spread this adaptive variant across a diverse set of environments.
Next-generation sequencing (NGS) technologies have become the standard for data generation in studies of population genomics, as the 1000 Genomes Project (1000G). However, these techniques are known ...to be problematic when applied to highly polymorphic genomic regions, such as the human leukocyte antigen (HLA) genes. Because accurate genotype calls and allele frequency estimations are crucial to population genomics analyses, it is important to assess the reliability of NGS data. Here, we evaluate the reliability of genotype calls and allele frequency estimates of the single-nucleotide polymorphisms (SNPs) reported by 1000G (phase I) at five HLA genes (HLA-A, -B, -C, -DRB1, and -DQB1). We take advantage of the availability of HLA Sanger sequencing of 930 of the 1092 1000G samples and use this as a gold standard to benchmark the 1000G data. We document that 18.6% of SNP genotype calls in HLA genes are incorrect and that allele frequencies are estimated with an error greater than ±0.1 at approximately 25% of the SNPs in HLA genes. We found a bias toward overestimation of reference allele frequency for the 1000G data, indicating mapping bias is an important cause of error in frequency estimation in this dataset. We provide a list of sites that have poor allele frequency estimates and discuss the outcomes of including those sites in different kinds of analyses. Because the HLA region is the most polymorphic in the human genome, our results provide insights into the challenges of using of NGS data at other genomic regions of high diversity.
The inference of genetic ancestry plays an increasingly prominent role in clinical, population, and forensic genetics studies. Several genotyping strategies and analytical methodologies have been ...developed over the last few decades to assign individuals to specific biogeographic regions. However, despite these efforts, ancestry inference in populations with a recent history of admixture, such as those in Brazil, remains a challenge. In admixed populations, proportion and components of genetic ancestry vary on different levels: (i) between populations; (ii) between individuals of the same population, and (iii) throughout the individual's genome. The present study evaluated 1171 admixed Brazilian samples to compare the genetic ancestry inferred by tri-/tetra-hybrid admixture models and evaluated different marker sets from those with small numbers of ancestry informative markers panels (AIMs), to high-density SNPs (HDSNP) and whole-genome-sequence (WGS) data. Analyses revealed greater variation in the correlation coefficient of ancestry components within and between admixed populations, especially for minority ancestral components. We also observed positive correlation between the number of markers in the AIMs panel and HDSNP/WGS. Furthermore, the greater the number of markers, the more accurate the tri-/tetra-hybrid admixture models.
The American continent was the last to be occupied by modern humans, and native populations bear the marks of recent expansions, bottlenecks, natural selection, and population substructure. Here we ...investigate how this demographic history has shaped genetic variation at the strongly selected HLA loci. In order to disentangle the relative contributions of selection and demography process, we assembled a dataset with genome-wide microsatellites and HLA-A, -B, -C, and -DRB1 typing data for a set of 424 Native American individuals. We find that demographic history explains a sizeable fraction of HLA variation, both within and among populations. A striking feature of HLA variation in the Americas is the existence of alleles which are present in the continent but either absent or very rare elsewhere in the world. We show that this feature is consistent with demographic history (i.e., the combination of changes in population size associated with bottlenecks and subsequent population expansions). However, signatures of selection at HLA loci are still visible, with significant evidence selection at deeper timescales for most loci and populations, as well as population differentiation at HLA loci exceeding that seen at neutral markers.
In this study, the chemical composition of the essential oil (EO) extracted from Croton blanchetianus Baill leaves was identified, and antimicrobial and antibiofilm activities against Staphylococcus ...aureus, Staphylococcus epidermidis, and Escherichia coli strains were determined. Moreover, the effects of EO in combination with ampicillin and tetracycline were investigated. Thirty‐four components, mainly mono‐and sesquiterpenes that represented 94.05 % of the chemical composition, were identified in the EO. The EO showed bacteriostatic and bactericidal activities against all strains tested. Furthermore, the EO showed a synergistic effect with ampicillin and tetracycline. EO significantly inhibited biofilm formation and reduced the number of viable cells in biofilms. The EO may be a promising natural product for preventing bacterial biofilm infections.
The analysis of genomic data (~400,000 autosomal SNPs) enabled the reliable estimation of inbreeding levels in a sample of 541 individuals sampled from a highly admixed Brazilian population isolate ...(an African-derived quilombo in the State of São Paulo). To achieve this, different methods were applied to the joint information of two sets of markers (one complete and another excluding loci in patent linkage disequilibrium). This strategy allowed the detection and exclusion of markers that biased the estimation of the average population inbreeding coefficient (Wright's fixation index FIS), which value was eventually estimated as around 1% using any of the methods we applied. Quilombo demographic inferences were made by analyzing the structure of runs of homozygosity (ROH), which were adapted to cope with a highly admixed population with a complex foundation history. Our results suggest that the amount of ROH <2Mb of admixed populations should be somehow proportional to the genetic contribution from each parental population.
An immunogenetic view of COVID-19 Aguiar, Vitor R C; Augusto, Danillo G; Castelli, Erick C ...
Genetics and molecular biology,
01/2021, Letnik:
44, Številka:
1 Suppl 1
Journal Article
Recenzirano
Odprti dostop
Meeting the challenges brought by the COVID-19 pandemic requires an interdisciplinary approach. In this context, integrating knowledge of immune function with an understanding of how genetic ...variation influences the nature of immunity is a key challenge. Immunogenetics can help explain the heterogeneity of susceptibility and protection to the viral infection and disease progression. Here, we review the knowledge developed so far, discussing fundamental genes for triggering the innate and adaptive immune responses associated with a viral infection, especially with the SARS-CoV-2 mechanisms. We emphasize the role of the HLA and KIR genes, discussing what has been uncovered about their role in COVID-19 and addressing methodological challenges of studying these genes. Finally, we comment on questions that arise when studying admixed populations, highlighting the case of Brazil. We argue that the interplay between immunology and an understanding of genetic associations can provide an important contribution to our knowledge of COVID-19.
The aim of this study was to evaluate dietary supplementation of different levels of dehydrated bocaiuva pulp (DBP) on the productive performance of laying quails, and on lipid oxidation, and quality ...in their eggs. A total of 120 quails were distributed in a completely randomized design with six treatments (0%, 0.1%, 0.2%, 0.3%, 0.4% and 0.5% of DBP), five replicates and four birds per experimental unit. To evaluate lipid oxidation, the eggs were collected on five consecutive days at the end of the trial and distributed in a completely randomized experimental design in a 6 × 5 factorial scheme (eggs from quails fed different levels of DBP × evaluated fresh and after 7, 14, 21 and 28 days). The antioxidant potential of diets was improved (p < 0.05) when the DBP was added estimated as 2,2'‐azinobis‐3‐ethylbenzothiazolin‐6‐sulfonic acid (ABTS) free radical scavenging capacity. No effect (p > 0.05) was observed on feed intake, hen‐day egg production and feed conversion (kg/kg and kg/dz). There were no changes (p > 0.05) in the egg weight, Haugh unit, yolk index or eggshell percentage. Although no difference was observed (p > 0.05), when comparing each level with the control, a negative linear effect (p < 0.05) on specific gravity was observed. In addition, only the treatment with 0.5% pulp exhibited lower (p < 0.05) eggshell thickness compared with the control (0%). Thiobarbituric acid reactive substances (TBARS) analysis showed that as the dietary pulp level was increased, malondialdehyde content decreased linearly (p < 0.05) in the egg yolks, regardless of the storage period. Inclusion of DBP in the diets had no effect (p > 0.05) on the concentration of conjugated dienes in the eggs. The diets containing DBP showed a potential antioxidant effect, reducing the degree of lipid oxidation in egg yolk. However, no beneficial effects were observed on performance and egg quality.
•Delayed or insufficient humoral immune response to SARS-CoV-2 in patients with Turner syndrome (TS).•Lower interferon-γ production in volunteers with TS after stimulation with toll-like receptors ...7/8 agonists.•Higher cytotoxic activity by cluster of differentiation 8+ and natural killer cells after phorbol myristate acetate (PMA)/ionomycin stimuli in TS.
The X-chromosome contains the largest number of immune-related genes, which play a major role in COVID-19 symptomatology and susceptibility. Here, we had a unique opportunity to investigate, for the first time, COVID-19 outcomes in six unvaccinated young Brazilian patients with Turner syndrome (TS; 45, X0), including one case of critical illness in a child aged 10 years, to evaluate their immune response according to their genetic profile.
A serological analysis of humoral immune response against SARS-CoV-2, phenotypic characterization of antiviral responses in peripheral blood mononuclear cells after stimuli, and the production of cytotoxic cytokines of T lymphocytes and natural killer cells were performed in blood samples collected from the patients with TS during the convalescence period. Whole exome sequencing was also performed.
Our volunteers with TS showed a delayed or insufficient humoral immune response to SARS-CoV-2 (particularly immunoglobulin G) and a decrease in interferon-γ production by cluster of differentiation (CD)4+ and CD8+ T lymphocytes after stimulation with toll-like receptors 7/8 agonists. In contrast, we observed a higher cytotoxic activity in the volunteers with TS than the volunteers without TS after phorbol myristate acetate/ionomycin stimulation, particularly granzyme B and perforin by CD8+ and natural killer cells. Interestingly, two volunteers with TS carry rare genetic variants in genes that regulate type I and III interferon immunity.
Following previous reports in the literature for other conditions, our data showed that patients with TS may have an impaired immune response against SARS-CoV-2. Furthermore, other medical conditions associated with TS could make them more vulnerable to COVID-19.
The mutation age and local ancestry of chromosomal segments harbouring mutations associated with autosomal recessive (AR) disorders in Brazilian admixed populations remain unknown; additionally, ...inbreeding levels for these affected individuals continue to be estimated based on genealogical information. Here, we calculated inbreeding levels using a runs of homozygosity approach, mutation age and local ancestry to infer the origin of each chromosomal segments containing disorder-causing mutations in KLC2, IMPA1, MED25 and WNT7A. Genotyped data were generated from 18 patients affected by AR diseases and combined to the 1000 genome project (1KGP) and Simons genome diversity project (SGDP) databases to infer local ancestry. We found a major European contribution for mutated haplotypes with recent mutation age and inbreeding values found only in Native American and Middle East individuals. These results contribute to identifying the origin of and to understanding how these diseases are maintained and spread in Brazilian and world populations.
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