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1.
BMC Infect Dis ; 20(1): 750, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33050903

RESUMO

BACKGROUND: Tuberculosis (TB) is caused by Mycobacterium tuberculosis complex (MTBC). Mapping the genetic diversity of MTBC in high TB burden country like Ethiopia is important to understand principles of the disease transmission and to strengthen the regional TB control program. The aim of this study was to investigate the genetic diversity of Mycobacterium tuberculosis complex (MTBC) isolates circulating in the South Omo, southern Ethiopia. METHODS: MTBC isolates (N = 156) were genetically analyzed using spacer oligotyping (spoligotyping) and mycobacterial interspersed repetitive unit-variable number of tandem repeat (MIRU-VNTR) typing. Major lineages and lineages were identified using MTBC databases. Logistic regression was used to correlate patient characteristics with strain clustering. RESULTS: The study identified Euro-American (EA), East-African-Indian (EAI), Indo-Oceanic (IO), Lineage_7/Aethiops vertus, Mycobacterium bovis and Mycobacterium africanum major lineages in proportions of 67.3% (105/156), 22.4% (35/156), 6.4% (10/156), 1.9% (3/156), 1.3% (2/156) and 0.6% (1/156), respectively. Lineages identified were Delhi/CAS 23.9% (37/155), Ethiopia_2 20.6% (32/155), Haarlem 14.2% (22/155), URAL 14.2%(22/155), Ethiopia_3 8.4% (13/155), TUR 6.5% (10/155), Lineage_7/Aethiops vertus 1.9% (3/155), Bovis 1.3% (2/155), LAM 1.3% (2/155), EAI 0.6% (1/155), X 0.6% (1/155) and Ethiopia H37Rv-like strain 0.6% (1/155). Of the genotyped isolates 5.8% (9/155) remained unassigned. The recent transmission index (RTI) was 3.9%. Orphan strains compared to shared types (AOR: 0.09, 95% CI: 0.04-0.25) were associated with reduced odds of clustering. The dominant TB lineage in pastoral areas was EAI and in non-pastoral areas was EA. CONCLUSION: The epidemiological data, highly diverse MTBC strains and a low RTI in South Omo, provide information contributing to the TB Control Program of the country.


Assuntos
Variação Genética , Mycobacterium bovis/genética , Mycobacterium tuberculosis/genética , Tuberculose Pulmonar/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Etiópia/epidemiologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Repetições Minissatélites/genética , Epidemiologia Molecular , Reação em Cadeia da Polimerase Multiplex , Mycobacterium bovis/isolamento & purificação , Mycobacterium tuberculosis/isolamento & purificação , Escarro/microbiologia , Tuberculose Pulmonar/microbiologia , Adulto Jovem
2.
Nat Commun ; 11(1): 4954, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009396

RESUMO

Genetic variation is of crucial importance for crop improvement. Landraces are valuable sources of diversity, but for quantitative traits efficient strategies for their targeted utilization are lacking. Here, we map haplotype-trait associations at high resolution in ~1000 doubled-haploid lines derived from three maize landraces to make their native diversity for early development traits accessible for elite germplasm improvement. A comparative genomic analysis of the discovered haplotypes in the landrace-derived lines and a panel of 65 breeding lines, both genotyped with 600k SNPs, points to untapped beneficial variation for target traits in the landraces. The superior phenotypic performance of lines carrying favorable landrace haplotypes as compared to breeding lines with alternative haplotypes confirms these findings. Stability of haplotype effects across populations and environments as well as their limited effects on undesired traits indicate that our strategy has high potential for harnessing beneficial haplotype variation for quantitative traits from genetic resources.


Assuntos
Haplótipos/genética , Característica Quantitativa Herdável , Zea mays/genética , Biblioteca Gênica , Variação Genética , Genoma de Planta , Estudo de Associação Genômica Ampla , Haploidia , Melhoramento Vegetal , Análise de Componente Principal , Zea mays/crescimento & desenvolvimento
3.
Am J Bot ; 107(9): 1296-1308, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-33001458

RESUMO

PREMISE: Recent phylogeographic work suggests the existence of latitudinal gradients in genetic diversity in northern Mexican plants, but very few studies have examined plants of the Chihuahuan Desert. Tidestromia lanuginosa is a morphologically variable annual species whose distribution includes the Chihuahuan Desert Region. Here we undertook phylogeographic analyses of chloroplast loci in this species to test whether genetic diversity and differentiation of Mexican populations of T. lanuginosa change along a latitudinal gradient and whether diversity is higher in Coahuila, consistent with ideas of lower plant community turnover during the Pleistocene. METHODS: Haplotype network, maximum likelihood tree, and Bayesian phylogenetic haplotype were reconstructed, and genetic diversity was assessed among 26 populations. Barrier analysis was used to explore barriers to gene flow. RESULTS: Four major population groups were identified, corresponding with physiographic provinces in Mexico. Each population group displayed high levels of genetic structure, haplotype, and nucleotide diversity. Diversity was highest in southern populations across the species as a whole and among the Chihuahuan Desert populations. CONCLUSIONS: Tidestromia lanuginosa provides an important example of high phylogeographic and genetic diversity in plants of northern Mexico. Barriers to gene flow among the major population groups have most likely been due to a combination of orographic, climatic, and edaphic variables. The high genetic diversity of T. lanuginosa in southern and central Coahuila is consistent with the hypothesis of full-glacial refugia for arid-adapted plants in this area, and highlights the importance of this region as a center of diversity for the Chihuahuan Desert flora.


Assuntos
Variação Genética , Refúgio de Vida Selvagem , Teorema de Bayes , México , Filogenia
4.
Front Immunol ; 11: 2008, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013857

RESUMO

Coronavirus disease (COVID-19), caused by the virus SARS-CoV-2, is already responsible for more than 4.3 million confirmed cases and 295,000 deaths worldwide as of May 15, 2020. Ongoing efforts to control the pandemic include the development of peptide-based vaccines and diagnostic tests. In these approaches, HLA allelic diversity plays a crucial role. Despite its importance, current knowledge of HLA allele frequencies in South America is very limited. In this study, we have performed a literature review of datasets reporting HLA frequencies of South American populations, available in scientific literature and/or in the Allele Frequency Net Database. This allowed us to enrich the current scenario with more than 12.8 million data points. As a result, we are presenting updated HLA allelic frequencies based on country, including 91 alleles that were previously thought to have frequencies either under 5% or of an unknown value. Using alleles with an updated frequency of at least ≥5% in any South American country, we predicted epitopes in SARS-CoV-2 proteins using NetMHCpan (I and II) and MHC flurry. Then, the best predicted epitopes (class-I and -II) were selected based on their binding to South American alleles (Coverage Score). Class II predicted epitopes were also filtered based on their three-dimensional exposure. We obtained 14 class-I and four class-II candidate epitopes with experimental evidence (reported in the Immune Epitope Database and Analysis Resource), having good coverage scores for South America. Additionally, we are presenting 13 HLA-I and 30 HLA-II novel candidate epitopes without experimental evidence, including 16 class-II candidates in highly exposed conserved areas of the NTD and RBD regions of the Spike protein. These novel candidates have even better coverage scores for South America than those with experimental evidence. Finally, we show that recent similar studies presenting candidate epitopes also predicted some of our candidates but discarded them in the selection process, resulting in candidates with suboptimal coverage for South America. In conclusion, the candidate epitopes presented provide valuable information for the development of epitope-based strategies against SARS-CoV-2, such as peptide vaccines and diagnostic tests. Additionally, the updated HLA allelic frequencies provide a better representation of South America and may impact different immunogenetic studies.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Epitopos de Linfócito T/imunologia , Frequência do Gene , Antígenos HLA/genética , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Proteínas do Envelope Viral/imunologia , Alelos , Sequência de Aminoácidos , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Variação Genética , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/virologia , América do Sul/epidemiologia , Vacinas de Subunidades/imunologia , Vacinas Virais/imunologia
5.
Front Immunol ; 11: 2008, 2020.
Artigo em Inglês | MEDLINE | ID: covidwho-781995

RESUMO

Coronavirus disease (COVID-19), caused by the virus SARS-CoV-2, is already responsible for more than 4.3 million confirmed cases and 295,000 deaths worldwide as of May 15, 2020. Ongoing efforts to control the pandemic include the development of peptide-based vaccines and diagnostic tests. In these approaches, HLA allelic diversity plays a crucial role. Despite its importance, current knowledge of HLA allele frequencies in South America is very limited. In this study, we have performed a literature review of datasets reporting HLA frequencies of South American populations, available in scientific literature and/or in the Allele Frequency Net Database. This allowed us to enrich the current scenario with more than 12.8 million data points. As a result, we are presenting updated HLA allelic frequencies based on country, including 91 alleles that were previously thought to have frequencies either under 5% or of an unknown value. Using alleles with an updated frequency of at least ≥5% in any South American country, we predicted epitopes in SARS-CoV-2 proteins using NetMHCpan (I and II) and MHC flurry. Then, the best predicted epitopes (class-I and -II) were selected based on their binding to South American alleles (Coverage Score). Class II predicted epitopes were also filtered based on their three-dimensional exposure. We obtained 14 class-I and four class-II candidate epitopes with experimental evidence (reported in the Immune Epitope Database and Analysis Resource), having good coverage scores for South America. Additionally, we are presenting 13 HLA-I and 30 HLA-II novel candidate epitopes without experimental evidence, including 16 class-II candidates in highly exposed conserved areas of the NTD and RBD regions of the Spike protein. These novel candidates have even better coverage scores for South America than those with experimental evidence. Finally, we show that recent similar studies presenting candidate epitopes also predicted some of our candidates but discarded them in the selection process, resulting in candidates with suboptimal coverage for South America. In conclusion, the candidate epitopes presented provide valuable information for the development of epitope-based strategies against SARS-CoV-2, such as peptide vaccines and diagnostic tests. Additionally, the updated HLA allelic frequencies provide a better representation of South America and may impact different immunogenetic studies.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Epitopos de Linfócito T/imunologia , Frequência do Gene , Antígenos HLA/genética , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Proteínas do Envelope Viral/imunologia , Alelos , Sequência de Aminoácidos , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Variação Genética , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/virologia , América do Sul/epidemiologia , Vacinas de Subunidades/imunologia , Vacinas Virais/imunologia
6.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 2353-2356, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018479

RESUMO

Genome-wide association studies have identified genetic variants including rs13143308T in the homeobox gene Pitx2 associated with atrial fibrillation (AF) populations. However, the molecular mechanisms leading to AF due to the rs13143308T variant are poorly understood. Therefore, this study aims to investigate the effects of this variant-induced alteration in calcium handling on properties of Ca2+-transients (CaT) and spontaneous calcium-release events (SCaEs). Based on recent experimental data on variants-induced alterations in ryanodine receptor channels (RyR) and sarcoplasmic reticulum (SR) calcium ATPase 2a (SERCA2a), we incorporated modifications to calcium handling into a previously published model of the human atrial cardiomyocyte with a spatial representation of calcium wave propagation. We identified that the rs13143308T variant has a higher incidence of spontaneous membrane depolarizations and amplitude of CaT than atrial myocytes without this variant. We showed a higher density of SCaEs and content of SR Ca2+ in atrial myocytes with the rs13143308T risk variant. Further computational analysis revealed that these calcium-mediated triggered activities were mainly linked to the gain of SERCA2a function but not the RyR2 dysfunction. Taken together, our model provides a powerful tool for assessing the impact of genetic variants in Pitx2, and these simulated results enhance our understanding of the molecular mechanisms underlying Pitx2-induced AF.


Assuntos
Fibrilação Atrial , Cálcio , Fibrilação Atrial/genética , Cálcio/metabolismo , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Canal de Liberação de Cálcio do Receptor de Rianodina/genética
7.
Viruses ; 12(10)2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-33050264

RESUMO

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), responsible for the ongoing coronavirus disease (COVID-19) pandemic, is frequently shed in faeces during infection, and viral RNA has recently been detected in sewage in some countries. We have investigated the presence of SARS-CoV-2 RNA in wastewater samples from South-East England between 14th January and 12th May 2020. A novel nested RT-PCR approach targeting five different regions of the viral genome improved the sensitivity of RT-qPCR assays and generated nucleotide sequences at sites with known sequence polymorphisms among SARS-CoV-2 isolates. We were able to detect co-circulating virus variants, some specifically prevalent in England, and to identify changes in viral RNA sequences with time consistent with the recently reported increasing global dominance of Spike protein G614 pandemic variant. Low levels of viral RNA were detected in a sample from 11th February, 3 days before the first case was reported in the sewage plant catchment area. SARS-CoV-2 RNA concentration increased in March and April, and a sharp reduction was observed in May, showing the effects of lockdown measures. We conclude that viral RNA sequences found in sewage closely resemble those from clinical samples and that environmental surveillance can be used to monitor SARS-CoV-2 transmission, tracing virus variants and detecting virus importations.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Esgotos/virologia , Betacoronavirus/isolamento & purificação , Inglaterra/epidemiologia , Monitoramento Ambiental , Variação Genética , Genoma Viral/genética , Humanos , Pandemias , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de DNA , Águas Residuárias/virologia
8.
Zootaxa ; 4801(1): zootaxa.4801.1.3, 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-33056672

RESUMO

More than 100 species have been referred to Rhamdia since its description, but in the last revision of the genus more than two decades ago, only eleven species have been considered as valid. Rhamdia quelen was then redefined to include 47 junior synonyms, resulting in a species with a large distribution in the Neotropics, from Mexico to Argentina. Populations of Rhamdia from west of the Andes have been recently removed from the synonymy of R. quelen, and currently there are 27 species recognized in the genus. Most cis-Andean populations, however, remain referred to the R. quelen species complex. In this paper, we use species delimitation methods and multilocus phylogenetic analyses to delimit the species contained in the R. quelen species complex in cis-Andean river drainages. Eighteen MOTUs in the gene tree were recovered with high support. We further demonstrate that the previous designation of a neotype for R. quelen is invalid, and has to be replaced by the proper designation of a neotype from the type locality of the species. The neotype is designated herein and R. quelen is diagnosed and redescribed.


Assuntos
Peixes-Gato , Animais , Variação Genética , Filogenia , América do Sul
9.
Acta amaz ; 50(3): 204-212, jul. - set. 2020.
Artigo em Inglês | LILACS | ID: biblio-1118824

RESUMO

Rosewood, Aniba rosaeodora is an endangered species in Amazon forests and its natural stands have been heavily depleted due to over-exploitation for the cosmetic industry. This study aimed to investigate the genetic diversity and population structure of 90 rosewood accessions from eight localities in the Peruvian Amazon through 11 Inter Simple Sequence Repeats (ISSR) primers. The ISSR primers produced a sum of 378 bands, of which 375 (99.2%) were polymorphic, with an average polymorphism information content (PIC) value of 0.774. The mean effective number of alleles (Ne), Shannon informative index (I), gene diversity (He) and total gene diversity (Ht) were 1.485, 0.294, 0.453 and 0.252, respectively. Analysis of molecular variance (AMOVA) showed the presence of maximum variability within populations (88%). The Structure algorithm, neighbor joining and principal coordinate analysis (PCoA) grouped the 90 rosewood accessions into three main populations (A, B and C). Diversity indices at the inter-population level revealed a greater genetic diversity in population A, due to higher gene flow. The neighbor-joining analysis grouped populations A and B, while population C was found to be divergent at the inter population level. We concluded that population A reflects higher genetic diversity and should be prioritized for future management and conservation plans. (AU)


Assuntos
Variação Genética , Espécies em Perigo de Extinção , Fluxo Gênico
10.
Acta amaz ; 50(3): 232-238, jul. - set. 2020.
Artigo em Inglês | LILACS | ID: biblio-1118836

RESUMO

The genus Bryconcomprises fish species of significant socioeconomic and biological importance in Brazil. Despite that, the genetic knowledge about these species is scarce, especially regardingBrycon falcatus. Thus, the objective of this study was to evaluate the transferability of heterologous microsatellite primers inB. falcatus for the first time. Heterologous primers obtained from B. opalinus, B. hilarii, B. insignis, B. orbignyanus, B. amazonicus, Prochilodus argenteus, Prochilodus lineatus, Piaractus mesopotamicus, and Colossoma macropomum were evaluated. The primers that showed the best amplification patterns were applied to a sample of 22 individuals and the genetic parameters were calculated. Nine primers displayed satisfactory cross-amplification withB. falcatus: BoM5 (Brycon opalinus); Bh8, Bh13 and Bh16 (B. hilarii); Borg59 (B. orbignyanus); Bag22 (B. amazonicus); Par12 and Par80 (P. argenteus), and Cm1A8 (C. macropomum). The genetic parameters (number of alleles, effective alleles, allele richness, and expected and observed heterozygosity) and the polymorphic information content (PIC) confirmed the viability of these primers for population genetics analyses. Our study demonstrates the potential of transferability of microsatellite markers from related species and even different genera to B. falcatus, providing usefull tools for future population genetic studies in this species. (AU)


Assuntos
Variação Genética , Repetições de Microssatélites , Parâmetros/classificação , Genética Populacional
12.
PLoS One ; 15(9): e0238344, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32881907

RESUMO

A novel severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) causing COVID-19 pandemic in humans, recently emerged and has exported in more than 200 countries as a result of rapid spread. In this study, we have made an attempt to investigate the SARS-CoV-2 genome reported from 13 different countries, identification of mutations in major coronavirus proteins of these different SARS-CoV-2 genomes and compared with SARS-CoV. These thirteen complete genome sequences of SARS-CoV-2 showed high identity (>99%) to each other, while they shared 82% identity with SARS-CoV. Here, we performed a very systematic mutational analysis of SARS-CoV-2 genomes from different geographical locations, which enabled us to identify numerous unique features of this viral genome. This includes several important country-specific unique mutations in the major proteins of SARS-CoV-2 namely, replicase polyprotein, spike glycoprotein, envelope protein and nucleocapsid protein. Indian strain showed mutation in spike glycoprotein at R408I and in replicase polyprotein at I671T, P2144S and A2798V,. While the spike protein of Spain & South Korea carried F797C and S221W mutation, respectively. Likewise, several important country specific mutations were analyzed. The effect of mutations of these major proteins were also investigated using various in silico approaches. Main protease (Mpro), the therapeutic target protein of SARS with maximum reported inhibitors, was thoroughly investigated and the effect of mutation on the binding affinity and structural dynamics of Mpro was studied. It was found that the R60C mutation in Mpro affects the protein dynamics, thereby, affecting the binding of inhibitor within its active site. The implications of mutation on structural characteristics were determined. The information provided in this manuscript holds great potential in further scientific research towards the design of potential vaccine candidates/small molecular inhibitor against COVID19.


Assuntos
Betacoronavirus/genética , Cisteína Endopeptidases/genética , Genoma Viral , Mutação , Proteínas do Nucleocapsídeo/genética , Glicoproteína da Espícula de Coronavírus/genética , Proteínas do Envelope Viral/genética , Proteínas não Estruturais Virais/genética , Betacoronavirus/classificação , Cisteína Endopeptidases/química , Variação Genética , Simulação de Dinâmica Molecular , Proteínas do Nucleocapsídeo/química , Filogenia , Glicoproteína da Espícula de Coronavírus/química , Proteínas do Envelope Viral/química , Proteínas não Estruturais Virais/química
13.
Zhongguo Zhong Yao Za Zhi ; 45(15): 3659-3665, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32893555

RESUMO

As a traditional Chinese medicinal material, Chrysosplenium is urgently needed for genetic resource investigation and protection research due to the decrease of its wild resources in recent years. After investigating the wild resources, we conducted genetic polymorphism and clustering studies of 24 species(a total of 36 samples) of Chrysosplenium using SRAP technique. The results showed that a total of 374 polymorphic bands were obtained using 18 pairs of SRAP primers to amplify these samples, on average of 20.7 bands for each primer pair. We used the biological software to analyze the population's genetic parameter and got the N_a value as 2.000 0, N_(e )value as 1.408 4, the average Nei's index as 0.263 5, and the average Shannon information index as 0.419 1. UPGMA cluster analysis showed that all the samples can be divided into three major groups at the genetic similarity coefficient of 0.70: there are 18 species(24 samples) gathered for the Ⅰ groups, 3 species or variation(7 samples) for Ⅱ groups, and 3 species(5 samples) for Ⅲ groups. The differences of these Chrysosplenium species at the molecular level are consistent with that of their geographical and ecological distribution. At the same time, we used SRAP technology to construct 36 DNA digital fingerprints of Chrysosplenium and obtained the unique molecular identification band type of each material. These results will provide effective methods and reliable basis for the identification, protection and genetic diversity analysis of the germplasm resources of Chrysosplenium, and lay a foundation for the further development and utilization of them.


Assuntos
Impressões Digitais de DNA , Variação Genética , Análise por Conglomerados , Marcadores Genéticos , Filogenia , Polimorfismo Genético
14.
Proc Biol Sci ; 287(1934): 20201111, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32873205

RESUMO

How genetic variation arises and persists over evolutionary time despite the depleting effects of natural selection remains a long-standing question. Here, we investigate the impacts of two extreme forms of population regulation-at the level of the total, mixed population (hard selection) and at the level of local, spatially distinct patches (soft selection)-on the emergence and fate of diversity under strong divergent selection. We find that while the form of population regulation has little effect on rates of diversification, it can modulate the long-term fate of genetic variation, diversity being more readily maintained under soft selection compared to hard selection. The mechanism responsible for coexistence is negative frequency-dependent selection which, while present initially under both forms of population regulation, persists over the long-term only under soft selection. Importantly, coexistence is robust to continued evolution of niche specialist types under soft selection but not hard selection. These results suggest that soft selection could be a general mechanism for the maintenance of ecological diversity over evolutionary time scales.


Assuntos
Evolução Biológica , Seleção Genética , Animais , Ecossistema , Variação Genética , Densidade Demográfica
15.
Proc Biol Sci ; 287(1934): 20200962, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32873209

RESUMO

Although polyploidy is widespread across the plant Tree of Life, its long-term evolutionary significance is still poorly understood. Here, we examine the effects of polyploidy in explaining the large-scale evolutionary patterns within angiosperms by focusing on a single family exhibiting extensive interspecific variation in chromosome numbers. We inferred ploidy from haploid chromosome numbers for 80% of species in the most comprehensive species-level chronogram for the Brassicaceae. After evaluating a total of 94 phylogenetic models of diversification, we found that ploidy influences diversification rates across the Brassicaceae. We also found that despite diversifying at a similar rate to diploids, polyploids have played a significant role in driving present-day differences in species richness among clades. Overall, in addition to highlighting the complexity in the evolutionary consequences of polyploidy, our results suggest that rare successful polyploids persist while significantly contributing to the long-term evolution of clades. Our findings further indicate that polyploidy has played a major role in driving the long-term evolution of the Brassicaceae and highlight the potential of polyploidy in shaping present-day diversity patterns across the plant Tree of Life.


Assuntos
Brassicaceae/genética , Diploide , Poliploidia , Evolução Biológica , Variação Genética , Genoma de Planta , Magnoliopsida , Filogenia , Ploidias
16.
Nat Commun ; 11(1): 4719, 2020 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948767

RESUMO

A small number of de novo assembled human genomes have been reported to date, and few have been complemented with population-based genetic variation, which is particularly important for North Africa, a region underrepresented in current genome-wide references. Here, we combine long- and short-read whole-genome sequencing data with recent assembly approaches into a de novo assembly of an Egyptian genome. The assembly demonstrates well-balanced quality metrics and is complemented with variant phasing via linked reads into haploblocks, which we associate with gene expression changes in blood. To construct an Egyptian genome reference, we identify genome-wide genetic variation within a cohort of 110 Egyptian individuals. We show that differences in allele frequencies and linkage disequilibrium between Egyptians and Europeans may compromise the transferability of European ancestry-based genetic disease risk and polygenic scores, substantiating the need for multi-ethnic genome references. Thus, the Egyptian genome reference will be a valuable resource for precision medicine.


Assuntos
Grupos Étnicos/genética , Genética Populacional , Genômica , Egito , Frequência do Gene , Variação Genética , Genoma Humano , Humanos , Desequilíbrio de Ligação , Masculino , Medicina de Precisão , Sequenciamento Completo do Genoma
17.
Genome Res ; 30(10): 1434-1448, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32878977

RESUMO

The human pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the major pandemic of the twenty-first century. We analyzed more than 4700 SARS-CoV-2 genomes and associated metadata retrieved from public repositories. SARS-CoV-2 sequences have a high sequence identity (>99.9%), which drops to >96% when compared to bat coronavirus genome. We built a mutation-annotated reference SARS-CoV-2 phylogeny with two main macro-haplogroups, A and B, both of Asian origin, and more than 160 sub-branches representing virus strains of variable geographical origins worldwide, revealing a rather uniform mutation occurrence along branches that could have implications for diagnostics and the design of future vaccines. Identification of the root of SARS-CoV-2 genomes is not without problems, owing to conflicting interpretations derived from either using the bat coronavirus genomes as an outgroup or relying on the sampling chronology of the SARS-CoV-2 genomes and TMRCA estimates; however, the overall scenario favors haplogroup A as the ancestral node. Phylogenetic analysis indicates a TMRCA for SARS-CoV-2 genomes dating to November 12, 2019, thus matching epidemiological records. Sub-haplogroup A2 most likely originated in Europe from an Asian ancestor and gave rise to subclade A2a, which represents the major non-Asian outbreak, especially in Africa and Europe. Multiple founder effect episodes, most likely associated with super-spreader hosts, might explain COVID-19 pandemic to a large extent.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/epidemiologia , Genoma Viral/genética , Pneumonia Viral/epidemiologia , Animais , Ásia/epidemiologia , Sequência de Bases/genética , Quirópteros/virologia , Mapeamento Cromossômico , Europa (Continente)/epidemiologia , Evolução Molecular , Variação Genética/genética , Humanos , Pandemias , Filogenia , Filogeografia , Homologia de Sequência do Ácido Nucleico
19.
PLoS One ; 15(9): e0237792, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32881892

RESUMO

BACKGROUND: Ewing sarcoma (EwS) is a rare, aggressive solid tumor of childhood, adolescence and young adulthood associated with pathognomonic EWSR1-ETS fusion oncoproteins altering transcriptional regulation. Genome-wide association studies (GWAS) have identified 6 common germline susceptibility loci but have not investigated low-frequency inherited variants with minor allele frequencies below 5% due to limited genotyped cases of this rare tumor. METHODS: We investigated the contribution of rare and low-frequency variation to EwS susceptibility in the largest EwS genome-wide association study to date (733 EwS cases and 1,346 unaffected controls of European ancestry). RESULTS: We identified two low-frequency variants, rs112837127 and rs2296730, on chromosome 20 that were associated with EwS risk (OR = 0.186 and 2.038, respectively; P-value < 5×10-8) and located near previously reported common susceptibility loci. After adjusting for the most associated common variant at the locus, only rs112837127 remained a statistically significant independent signal (OR = 0.200, P-value = 5.84×10-8). CONCLUSIONS: These findings suggest rare variation residing on common haplotypes are important contributors to EwS risk. IMPACT: Motivate future targeted sequencing studies for a comprehensive evaluation of low-frequency and rare variation around common EwS susceptibility loci.


Assuntos
Loci Gênicos , Predisposição Genética para Doença , Variação Genética , Células Germinativas/metabolismo , Sarcoma de Ewing/genética , Estudo de Associação Genômica Ampla , Humanos , Desequilíbrio de Ligação/genética , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética
20.
ACS Chem Neurosci ; 11(19): 2944-2961, 2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-32870641

RESUMO

A significant proportion of people who test positive for COVID-19 have chemosensory deficits. However, the reported prevalence of these deficits in smell and taste varies widely, and the reason for the differences between studies is unclear. We determined the pooled prevalence of such chemosensory deficits in a systematic review and meta-analysis. We searched the COVID-19 portfolio of the National Institutes of Health for studies that reported the prevalence of smell or taste deficits or both in patients diagnosed with COVID-19. One-hundred-four studies reporting on 38 198 patients qualified and were subjected to a systematic review and meta-analysis. Estimated random prevalence of olfactory dysfunction was 43.0%, that of taste dysfunction was 44.6%, and that of overall chemosensory dysfunction was 47.4%. We examined the effects of age, gender, disease severity, and ethnicity on chemosensory dysfunction. Prevalence of smell or taste dysfunction or both decreased with older age, male gender, and disease severity. Ethnicity was highly significant: Caucasians had a three times higher prevalence of chemosensory dysfunctions (54.8%) than Asians (17.7%). The finding of geographic differences points to two causes that are not mutually exclusive. A virus mutation (D614G) may cause differing infectivity, while at the host level genetic, ethnicity-specific variants of the virus-binding entry proteins may facilitate virus entry in the olfactory epithelium and taste buds. Both explanations have major implications for infectivity, diagnosis, and management of the COVID-19 pandemic.


Assuntos
Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Infecções por Coronavirus/fisiopatologia , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Transtornos do Olfato/etnologia , Pneumonia Viral/fisiopatologia , Fatores Etários , Betacoronavirus/genética , Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Grupos Étnicos , Variação Genética , Humanos , Transtornos do Olfato/epidemiologia , Transtornos do Olfato/fisiopatologia , Pandemias , Peptidil Dipeptidase A/genética , Pneumonia Viral/epidemiologia , Prevalência , Serina Endopeptidases/genética , Índice de Gravidade de Doença , Fatores Sexuais
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