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1.
Ann Lab Med ; 41(2): 129-138, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33063674

RESUMEN

Since its first report in December 2019, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly emerged as a pandemic affecting nearly all countries worldwide. As the COVID-19 pandemic progresses, the need to identify genetic risk factors for susceptibility to this serious illness has emerged. Host genetic factors, along with other risk factors may help determine susceptibility to respiratory tract infections. It is hypothesized that the ACE2 gene, encoding angiotensin-converting enzyme 2 (ACE2), is a genetic risk factor for SARS-CoV-2 infection and is required by the virus to enter cells. Together with ACE2, transmembrane protease serine 2 (TMPRSS2) and dipeptidyl peptidase-4 (DPP4) also play an important role in disease severity. Evaluating the role of genetic variants in determining the direction of respiratory infections will help identify potential drug target candidates for further study in COVID-19 patients. We have summarized the latest reports demonstrating that ACE2 variants, their expression, and epigenetic factors may influence an individual's susceptibility to SARS-CoV-2 infection and disease outcome.


Asunto(s)
Betacoronavirus/genética , Infecciones por Coronavirus/patología , Variación Genética , Neumonía Viral/patología , Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/virología , Dipeptidil Peptidasa 4/genética , Dipeptidil Peptidasa 4/metabolismo , Susceptibilidad a Enfermedades , Expresión Génica , Humanos , Pandemias , Peptidil-Dipeptidasa A/química , Peptidil-Dipeptidasa A/genética , Peptidil-Dipeptidasa A/metabolismo , Neumonía Viral/virología , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismo , Índice de Severidad de la Enfermedad
2.
BMC Infect Dis ; 20(1): 816, 2020 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-33167886

RESUMEN

BACKGROUND: The prevalence of Staphylococcus aureus varies depending on the healthcare facility, region and country. To understand its genetic diversity, transmission, dissemination, epidemiology and evolution in a particular geographical location, it is important to understand the similarities and variations in the population being studied. This can be achieved by using various molecular characterisation techniques. This study aimed to provide detailed molecular characterisation of South African mecA-positive S. aureus blood culture isolates by describing the SCCmec types, spa types and to lesser extent, the sequence types obtained from two consecutive national surveillance studies. METHODS: S. aureus blood culture isolates from a national laboratory-based and enhanced surveillance programme were identified and antimicrobial susceptibility testing was performed using automated systems. A real-time PCR assay confirmed the presence of the methicillin-resistance determinant, mecA. Conventional PCR assays were used to identify the SCCmec type and spa type, which was subsequently analysed using the Ridom StaphType™ software. Multilocus sequence typing was performed on selected isolates using conventional methods. MRSA clones were defined by their sequence type (ST), SCCmec type and spa type. RESULTS: A detailed description of findings is reported in this manuscript. SCCmec type III predominated overall followed by type IV. A total of 71 different spa types and 24 novel spa types were observed. Spa type t037 was the most common and predominated throughout followed by t1257. Isolates were multidrug resistant; isolates belonging to all SCCmec types were resistant to most of the antibiotics with the exception of type I; isolates with spa type t045 showed resistance to all antibiotics except vancomycin. The most diverse SCCmec-spa type complex was composed of the SCCmec type IV element and 53 different spa types. CONCLUSION: Although ST data was limited, thereby limiting the number of clones that could be identified, the circulating clones were relatively diverse.


Asunto(s)
Proteínas Bacterianas/genética , Variación Genética , Secuencias Repetitivas Esparcidas/genética , Staphylococcus aureus Resistente a Meticilina/genética , Proteínas de Unión a las Penicilinas/genética , Infecciones Estafilocócicas/epidemiología , Proteína Estafilocócica A/genética , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Proteínas Bacterianas/sangre , Cultivo de Sangre , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple/genética , Humanos , Meticilina/farmacología , Meticilina/uso terapéutico , Resistencia a la Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Proteínas de Unión a las Penicilinas/sangre , Reacción en Cadena en Tiempo Real de la Polimerasa , Sudáfrica/epidemiología , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Vancomicina/farmacología , Vancomicina/uso terapéutico
3.
PLoS One ; 15(11): e0240345, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33170902

RESUMEN

In late December 2019, an emerging viral infection COVID-19 was identified in Wuhan, China, and became a global pandemic. Characterization of the genetic variants of SARS-CoV-2 is crucial in following and evaluating it spread across countries. In this study, we collected and analyzed 3,067 SARS-CoV-2 genomes isolated from 55 countries during the first three months after the onset of this virus. Using comparative genomics analysis, we traced the profiles of the whole-genome mutations and compared the frequency of each mutation in the studied population. The accumulation of mutations during the epidemic period with their geographic locations was also monitored. The results showed 782 variants sites, of which 512 (65.47%) had a non-synonymous effect. Frequencies of mutated alleles revealed the presence of 68 recurrent mutations, including ten hotspot non-synonymous mutations with a prevalence higher than 0.10 in this population and distributed in six SARS-CoV-2 genes. The distribution of these recurrent mutations on the world map revealed that certain genotypes are specific to geographic locations. We also identified co-occurring mutations resulting in the presence of several haplotypes. Moreover, evolution over time has shown a mechanism of mutation co-accumulation which might affect the severity and spread of the SARS-CoV-2. The phylogentic analysis identified two major Clades C1 and C2 harboring mutations L3606F and G614D, respectively and both emerging for the first time in China. On the other hand, analysis of the selective pressure revealed the presence of negatively selected residues that could be taken into considerations as therapeutic targets. We have also created an inclusive unified database (http://covid-19.medbiotech.ma) that lists all of the genetic variants of the SARS-CoV-2 genomes found in this study with phylogeographic analysis around the world.


Asunto(s)
Betacoronavirus/genética , Variación Genética , Genoma Viral , Betacoronavirus/clasificación , Betacoronavirus/aislamiento & purificación , China , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Evolución Molecular , Humanos , Pandemias , Filogenia , Neumonía Viral/patología , Neumonía Viral/virología , Estructura Terciaria de Proteína , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/genética , Proteínas Virales/química , Proteínas Virales/genética
4.
Nat Commun ; 11(1): 5482, 2020 10 30.
Artículo en Inglés | MEDLINE | ID: mdl-33127893

RESUMEN

The current human reference genome is predominantly derived from a single individual and it does not adequately reflect human genetic diversity. Here, we analyze 338 high-quality human assemblies of genetically divergent human populations to identify missing sequences in the human reference genome with breakpoint resolution. We identify 127,727 recurrent non-reference unique insertions spanning 18,048,877 bp, some of which disrupt exons and known regulatory elements. To improve genome annotations, we linearly integrate these sequences into the chromosomal assemblies and construct a Human Diversity Reference. Leveraging this reference, an average of 402,573 previously unmapped reads can be recovered for a given genome sequenced to ~40X coverage. Transcriptomic diversity among these non-reference sequences can also be directly assessed. We successfully map tens of thousands of previously discarded RNA-Seq reads to this reference and identify transcription evidence in 4781 gene loci, underlining the importance of these non-reference sequences in functional genomics. Our extensive datasets are important advances toward a comprehensive reference representation of global human genetic diversity.


Asunto(s)
Variación Genética , Genoma Humano , Población/genética , Mapeo Cromosómico , Biología Computacional , Expresión Génica , Genómica , Técnicas de Genotipaje , Humanos , Anotación de Secuencia Molecular , RNA-Seq , Análisis de Secuencia de ADN , Transcriptoma , Secuenciación Completa del Genoma
5.
N Engl J Med ; 383(18): 1746-1756, 2020 10 29.
Artículo en Inglés | MEDLINE | ID: mdl-33027564

RESUMEN

BACKGROUND: The cause of most fetal anomalies is not determined prenatally. Exome sequencing has transformed genetic diagnosis after birth, but its usefulness for prenatal diagnosis is still emerging. Nonimmune hydrops fetalis (NIHF), a fetal abnormality that is often lethal, has numerous genetic causes; the extent to which exome sequencing can aid in its diagnosis is unclear. METHODS: We evaluated a series of 127 consecutive unexplained cases of NIHF that were defined by the presence of fetal ascites, pleural or pericardial effusions, skin edema, cystic hygroma, increased nuchal translucency, or a combination of these conditions. The primary outcome was the diagnostic yield of exome sequencing for detecting genetic variants that were classified as either pathogenic or likely pathogenic according to the criteria of the American College of Medical Genetics and Genomics. Secondary outcomes were the percentage of cases associated with specific genetic disorders and the proportion of variants that were inherited. RESULTS: In 37 of the 127 cases (29%), we identified diagnostic genetic variants, including those for disorders affecting the RAS-MAPK cell-signaling pathway (known as RASopathies) (30% of the genetic diagnoses); inborn errors of metabolism and musculoskeletal disorders (11% each); lymphatic, neurodevelopmental, cardiovascular, and hematologic disorders (8% each); and others. Prognoses ranged from a relatively mild outcome to death during the perinatal period. Overall, 68% of the cases (25 of 37) with diagnostic variants were autosomal dominant (of which 12% were inherited and 88% were de novo), 27% (10 of 37) were autosomal recessive (of which 95% were inherited and 5% were de novo), 1 was inherited X-linked recessive, and 1 was of uncertain inheritance. We identified potentially diagnostic variants in an additional 12 cases. CONCLUSIONS: In this large case series of 127 fetuses with unexplained NIHF, we identified a diagnostic genetic variant in approximately one third of the cases. (Funded by the UCSF Center for Maternal-Fetal Precision Medicine and others; ClinicalTrials.gov number, NCT03412760.).


Asunto(s)
Variación Genética , Hidropesía Fetal/diagnóstico , Hidropesía Fetal/genética , Diagnóstico Prenatal , Secuenciación del Exoma Completo , Femenino , Humanos , Embarazo , Pronóstico
6.
Zool Res ; 41(6): 705-708, 2020 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-33045776

RESUMEN

Since the first reported severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in December 2019, coronavirus disease 2019 (COVID-19) has become a global pandemic, spreading to more than 200 countries and regions worldwide. With continued research progress and virus detection, SARS-CoV-2 genomes and sequencing data have been reported and accumulated at an unprecedented rate. To meet the need for fast analysis of these genome sequences, the National Genomics Data Center (NGDC) of the China National Center for Bioinformation (CNCB) has established an online coronavirus analysis platform, which includes de novoassembly, BLAST alignment, genome annotation, variant identification, and variant annotation modules. The online analysis platform can be freely accessed at the 2019 Novel Coronavirus Resource (2019nCoVR) (https://bigd.big.ac.cn/ncov/online/tools).


Asunto(s)
Betacoronavirus/genética , Biología Computacional/métodos , Infecciones por Coronavirus/diagnóstico , Genoma Viral/genética , Genómica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Neumonía Viral/diagnóstico , Animales , Betacoronavirus/clasificación , Betacoronavirus/fisiología , China , Biología Computacional/organización & administración , Infecciones por Coronavirus/virología , Variación Genética , Humanos , Internet , Anotación de Secuencia Molecular , Pandemias , Neumonía Viral/virología
7.
Nat Commun ; 11(1): 4954, 2020 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-33009396

RESUMEN

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.


Asunto(s)
Haplotipos/genética , Carácter Cuantitativo Heredable , Zea mays/genética , Biblioteca de Genes , Variación Genética , Genoma de Planta , Estudio de Asociación del Genoma Completo , Haploidia , Fitomejoramiento , Análisis de Componente Principal , Zea mays/crecimiento & desarrollo
8.
Nat Commun ; 11(1): 5451, 2020 10 28.
Artículo en Inglés | MEDLINE | ID: mdl-33116142

RESUMEN

The genetics of phenotypic responses to changing environments remains elusive. Using whole-genome quantitative gene expression as a model, here we study how the genetic architecture of regulatory variation in gene expression changed in a population of fully sequenced inbred Drosophila melanogaster strains when flies developed in different environments (25 °C and 18 °C). We find a substantial fraction of the transcriptome exhibited genotype by environment interaction, implicating environmentally plastic genetic architecture of gene expression. Genetic variance in expression increases at 18 °C relative to 25 °C for most genes that have a change in genetic variance. Although the majority of expression quantitative trait loci (eQTLs) for the gene expression traits in the two environments are shared and have similar effects, analysis of the environment-specific eQTLs reveals enrichment of binding sites for two transcription factors. Finally, although genotype by environment interaction in gene expression could potentially disrupt genetic networks, the co-expression networks are highly conserved across environments. Genes with higher network connectivity are under stronger stabilizing selection, suggesting that stabilizing selection on expression plays an important role in promoting network robustness.


Asunto(s)
Drosophila melanogaster/genética , Interacción Gen-Ambiente , Animales , Femenino , Expresión Génica , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Genes de Insecto , Variación Genética , Genotipo , Masculino , Sitios de Carácter Cuantitativo , RNA-Seq , Temperatura , Transcriptoma
9.
Front Cell Infect Microbiol ; 10: 575613, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33123498

RESUMEN

Background: The ongoing pandemic of SARS-COV-2 has already infected more than eight million people worldwide. The majority of COVID-19 patients either are asymptomatic or have mild symptoms. Yet, about 15% of the cases experience severe complications and require intensive care. Factors determining disease severity are not yet fully characterized. Aim: Here, we investigated the within-host virus diversity in COVID-19 patients with different clinical manifestations. Methods: We compared SARS-COV-2 genetic diversity in 19 mild and 27 severe cases. Viral RNA was extracted from nasopharyngeal samples and sequenced using the Illumina MiSeq platform. This was followed by deep-sequencing analyses of SARS-CoV-2 genomes at both consensus and sub-consensus sequence levels. Results: Consensus sequences of all viruses were very similar, showing more than 99.8% sequence identity regardless of the disease severity. However, the sub-consensus analysis revealed significant differences in within-host diversity between mild and severe cases. Patients with severe symptoms exhibited a significantly (p-value 0.001) higher number of variants in coding and non-coding regions compared to mild cases. Analysis also revealed higher prevalence of some variants among severe cases. Most importantly, severe cases exhibited significantly higher within-host diversity (mean = 13) compared to mild cases (mean = 6). Further, higher within-host diversity was observed in patients above the age of 60 compared to the younger age group. Conclusion: These observations provided evidence that within-host diversity might play a role in the development of severe disease outcomes in COVID-19 patients; however, further investigations are required to elucidate this association.


Asunto(s)
Betacoronavirus/clasificación , Betacoronavirus/genética , Variación Genética/genética , Genoma Viral/genética , Índice de Severidad de la Enfermedad , Adulto , Anciano , Secuencia de Consenso/genética , Infecciones por Coronavirus/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/patología , ARN Viral/genética , Factores de Riesgo , Análisis de Secuencia de ARN , Adulto Joven
10.
Med Sci (Paris) ; 36(10): 945-948, 2020 Oct.
Artículo en Francés | MEDLINE | ID: mdl-33026341

RESUMEN

More than 10 million enslaved Africans were transported to the Americas between 1500 and 1900. Recent genetic studies investigate regional African ancestry components in present-day Africa-Americans, and allow comparison with the extensive records documenting these deportations. The genetic evidence generally agrees with the historical records but brings additional insights in this dark episode of human history.


Asunto(s)
Afroamericanos/genética , Personas Esclavizadas , Esclavización/historia , Genética de Población , África , Océano Atlántico , Comercio/historia , ADN Mitocondrial/análisis , ADN Mitocondrial/genética , Personas Esclavizadas/historia , Flujo Génico/fisiología , Variación Genética , Historia del Siglo XVI , Historia del Siglo XVII , Historia del Siglo XVIII , Historia del Siglo XIX , Humanos , Patrón de Herencia/genética , Estados Unidos
11.
PLoS One ; 15(10): e0239758, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33057367

RESUMEN

OBJECTIVE: People with HIV (PWH) continue to experience sensory neuropathy and neuropathic pain in the combination antiretroviral therapy (cART) era for unclear reasons. This study evaluated the role of iron in a previously reported association of iron-loading hemochromatosis (HFE) gene variants with reduced risk of neuropathy in PWH who received more neurotoxic cART, since an iron-related mechanism also might be relevant to neuropathic symptoms in PWH living in low-resource settings today. DESIGN: This time-to-event analysis addressed the impact of systemic iron levels on the rapidity of neuropathy onset in PWH who initiated cART. METHODS: Soluble transferrin receptor (sTFR), the sTFR-ferritin index of iron stores, and high-sensitivity C-reactive protein (hsCRP) levels were determined in stored baseline sera from participants of known HFE genotype from AIDS Clinical Trials Group (ACTG) Study 384, a multicenter randomized clinical trial that evaluated cART strategies. Associations with incident neuropathy were evaluated in proportional-hazards, time-to-event regression models, adjusting for potential confounders. RESULTS: Of 151 eligible participants with stored serum who were included in the original genetic study, 43 had cART-associated neuropathy; 108 had sufficient serum for analysis, including 30 neuropathy cases. Carriers of HFE variants had higher systemic iron (lower sTFR and sTFR-ferritin index) and lower hsCRP levels than non-carriers (all p<0.05). Higher sTFR or iron stores, the HFE 187C>G variant, and lower baseline hsCRP were associated with significantly delayed neuropathy in self-reported whites (n = 28; all p-values<0.05), independent of age, CD4+ T-cell count, plasma HIV RNA, and cART regimen. CONCLUSIONS: Higher iron stores, the HFE 187C>G variant, and lower hsCRP predicted delayed onset of neuropathy among self-reported white individuals initating cART. These findings require confirmation but may have implications for cART in HIV+ populations in areas with high endemic iron deficiency, especially those PWH in whom older, more neurotoxic antiretroviral drugs are occasionally still used.


Asunto(s)
Antirretrovirales/efectos adversos , Terapia Antirretroviral Altamente Activa/efectos adversos , Variación Genética/genética , Proteína de la Hemocromatosis/genética , Hierro/metabolismo , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/genética , Adulto , Antirretrovirales/uso terapéutico , Femenino , Ferritinas/genética , Genotipo , Infecciones por VIH/tratamiento farmacológico , Hemocromatosis/genética , Heterocigoto , Humanos , Masculino , Neuralgia/inducido químicamente , Neuralgia/genética , Receptores de Transferrina/genética
12.
BMC Bioinformatics ; 21(1): 452, 2020 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-33050876

RESUMEN

BACKGROUND: Any two unrelated people differ by about 20,000 missense mutations (also referred to as SAVs: Single Amino acid Variants or missense SNV). Many SAVs have been predicted to strongly affect molecular protein function. Common SAVs (> 5% of population) were predicted to have, on average, more effect on molecular protein function than rare SAVs (< 1% of population). We hypothesized that the prevalence of effect in common over rare SAVs might partially be caused by common SAVs more often occurring at interfaces of proteins with other proteins, DNA, or RNA, thereby creating subgroup-specific phenotypes. We analyzed SAVs from 60,706 people through the lens of two prediction methods, one (SNAP2) predicting the effects of SAVs on molecular protein function, the other (ProNA2020) predicting residues in DNA-, RNA- and protein-binding interfaces. RESULTS: Three results stood out. Firstly, SAVs predicted to occur at binding interfaces were predicted to more likely affect molecular function than those predicted as not binding (p value < 2.2 × 10-16). Secondly, for SAVs predicted to occur at binding interfaces, common SAVs were predicted more strongly with effect on protein function than rare SAVs (p value < 2.2 × 10-16). Restriction to SAVs with experimental annotations confirmed all results, although the resulting subsets were too small to establish statistical significance for any result. Thirdly, the fraction of SAVs predicted at binding interfaces differed significantly between tissues, e.g. urinary bladder tissue was found abundant in SAVs predicted at protein-binding interfaces, and reproductive tissues (ovary, testis, vagina, seminal vesicle and endometrium) in SAVs predicted at DNA-binding interfaces. CONCLUSIONS: Overall, the results suggested that residues at protein-, DNA-, and RNA-binding interfaces contributed toward predicting that common SAVs more likely affect molecular function than rare SAVs.


Asunto(s)
Aminoácidos/genética , Variación Genética , Ácidos Nucleicos/metabolismo , Proteínas/genética , Proteínas/metabolismo , Secuencia de Bases , Femenino , Humanos , Sustancias Macromoleculares/metabolismo , Masculino , Modelos Moleculares , Mutación Missense/genética , Unión Proteica , Reproducibilidad de los Resultados
13.
Nat Commun ; 11(1): 5445, 2020 10 28.
Artículo en Inglés | MEDLINE | ID: mdl-33116115

RESUMEN

Single-cell RNA sequencing studies on gene co-expression patterns could yield important regulatory and functional insights, but have so far been limited by the confounding effects of differentiation and cell cycle. We apply a tailored experimental design that eliminates these confounders, and report thousands of intrinsically covarying gene pairs in mouse embryonic stem cells. These covariations form a network with biological properties, outlining known and novel gene interactions. We provide the first evidence that miRNAs naturally induce transcriptome-wide covariations and compare the relative importance of nuclear organization, transcriptional and post-transcriptional regulation in defining covariations. We find that nuclear organization has the greatest impact, and that genes encoding for physically interacting proteins specifically tend to covary, suggesting importance for protein complex formation. Our results lend support to the concept of post-transcriptional RNA operons, but we further present evidence that nuclear proximity of genes may provide substantial functional regulation in mammalian single cells.


Asunto(s)
Núcleo Celular/genética , Redes Reguladoras de Genes , Mapas de Interacción de Proteínas , Animales , Línea Celular , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Técnicas de Inactivación de Genes , Variación Genética , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Células Madre Embrionarias de Ratones/citología , Células Madre Embrionarias de Ratones/metabolismo , RNA-Seq , Ribonucleasa III/deficiencia , Ribonucleasa III/genética , Ribonucleasa III/metabolismo , Análisis de la Célula Individual , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Transcriptoma
14.
Nat Commun ; 11(1): 5442, 2020 10 28.
Artículo en Inglés | MEDLINE | ID: mdl-33116128

RESUMEN

Miscanthus is a perennial wild grass that is of global importance for paper production, roofing, horticultural plantings, and an emerging highly productive temperate biomass crop. We report a chromosome-scale assembly of the paleotetraploid M. sinensis genome, providing a resource for Miscanthus that links its chromosomes to the related diploid Sorghum and complex polyploid sugarcanes. The asymmetric distribution of transposons across the two homoeologous subgenomes proves Miscanthus paleo-allotetraploidy and identifies several balanced reciprocal homoeologous exchanges. Analysis of M. sinensis and M. sacchariflorus populations demonstrates extensive interspecific admixture and hybridization, and documents the origin of the highly productive triploid bioenergy crop M. × giganteus. Transcriptional profiling of leaves, stem, and rhizomes over growing seasons provides insight into rhizome development and nutrient recycling, processes critical for sustainable biomass accumulation in a perennial temperate grass. The Miscanthus genome expands the power of comparative genomics to understand traits of importance to Andropogoneae grasses.


Asunto(s)
Poaceae/genética , Biomasa , Cromosomas de las Plantas/genética , Elementos Transponibles de ADN , Diploidia , Evolución Molecular , Regulación de la Expresión Génica de las Plantas , Variación Genética , Genoma de Planta , Genómica , Modelos Genéticos , Filogenia , Poaceae/clasificación , Poaceae/crecimiento & desarrollo , Poliploidía , Saccharum/genética , Estaciones del Año , Sorghum/genética
15.
Nat Commun ; 11(1): 5432, 2020 10 28.
Artículo en Inglés | MEDLINE | ID: mdl-33116134

RESUMEN

Adeno-associated virus (AAV) forms the basis for several commercial gene therapy products and for countless gene transfer vectors derived from natural or synthetic viral isolates that are under intense preclinical evaluation. Here, we report a versatile pipeline that enables the direct side-by-side comparison of pre-selected AAV capsids in high-throughput and in the same animal, by combining DNA/RNA barcoding with multiplexed next-generation sequencing. For validation, we create three independent libraries comprising 183 different AAV variants including widely used benchmarks and screened them in all major tissues in adult mice. Thereby, we discover a peptide-displaying AAV9 mutant called AAVMYO that exhibits superior efficiency and specificity in the musculature including skeletal muscle, heart and diaphragm following peripheral delivery, and that holds great potential for muscle gene therapy. Our comprehensive methodology is compatible with any capsids, targets and species, and will thus facilitate and accelerate the stratification of optimal AAV vectors for human gene therapy.


Asunto(s)
Proteínas de la Cápside/genética , Dependovirus/genética , Vectores Genéticos , Músculos/metabolismo , Músculos/virología , Animales , Cápside , Código de Barras del ADN Taxonómico , Femenino , Biblioteca de Genes , Terapia Genética/métodos , Variación Genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Ratones , Ratones Endogámicos C57BL , Mutación , Especificidad de Órganos
16.
Nat Commun ; 11(1): 5441, 2020 10 28.
Artículo en Inglés | MEDLINE | ID: mdl-33116138

RESUMEN

With global warming and climate change, breeding crop plants tolerant to high-temperature stress is of immense significance. tRNA 2-thiolation is a highly conserved form of tRNA modification among living organisms. Here, we report the identification of SLG1 (Slender Guy 1), which encodes the cytosolic tRNA 2-thiolation protein 2 (RCTU2) in rice. SLG1 plays a key role in the response of rice plants to high-temperature stress at both seedling and reproductive stages. Dysfunction of SLG1 results in plants with thermosensitive phenotype, while overexpression of SLG1 enhances the tolerance of plants to high temperature. SLG1 is differentiated between the two Asian cultivated rice subspecies, indica and japonica, and the variations at both promoter and coding regions lead to an increased level of thiolated tRNA and enhanced thermotolerance of indica rice varieties. Our results demonstrate that the allelic differentiation of SLG1 confers indica rice to high-temperature tolerance, and tRNA thiolation pathway might be a potential target in the next generation rice breeding for the warming globe.


Asunto(s)
Genes de Plantas , Oryza/genética , Oryza/fisiología , Termotolerancia/genética , Termotolerancia/fisiología , Variación Genética , Calentamiento Global , Modelos Biológicos , Fitomejoramiento , Proteínas de Plantas/genética , Proteínas de Plantas/fisiología , Regiones Promotoras Genéticas , Procesamiento Postranscripcional del ARN/genética , Procesamiento Postranscripcional del ARN/fisiología , ARN de Planta/metabolismo , ARN de Transferencia/metabolismo , Tionucleótidos/metabolismo
18.
Zootaxa ; 4801(1): zootaxa.4801.1.3, 2020 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-33056672

RESUMEN

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.


Asunto(s)
Bagres , Animales , Variación Genética , Filogenia , América del Sur
19.
Am J Bot ; 107(9): 1296-1308, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-33001458

RESUMEN

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.


Asunto(s)
Variación Genética , Refugio de Fauna , Teorema de Bayes , México , Filogenia
20.
BMC Infect Dis ; 20(1): 750, 2020 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-33050903

RESUMEN

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.


Asunto(s)
Variación Genética , Mycobacterium bovis/genética , Mycobacterium tuberculosis/genética , Tuberculosis Pulmonar/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Etiopía/epidemiología , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Repeticiones de Minisatélite/genética , Epidemiología Molecular , Reacción en Cadena de la Polimerasa Multiplex , Mycobacterium bovis/aislamiento & purificación , Mycobacterium tuberculosis/aislamiento & purificación , Esputo/microbiología , Tuberculosis Pulmonar/microbiología , Adulto Joven
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