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1.
Annu Rev Genomics Hum Genet ; 25(1): 183-209, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38640230

RESUMEN

Mycobacterium tuberculosis is considered by many to be the deadliest microbe, with the estimated annual cases numbering more than 10 million. The bacteria, including Mycobacterium africanum, are classified into nine major lineages and hundreds of sublineages, each with different geographical distributions and levels of virulence. The phylogeographic patterns can be a result of recent and early human migrations as well as coevolution between the bacteria and various human populations, which may explain why many studies on human genetic factors contributing to tuberculosis have not been replicable in different areas. Moreover, several studies have revealed the significance of interactions between human genetic variations and bacterial genotypes in determining the development of tuberculosis, suggesting coadaptation. The increased availability of whole-genome sequence data from both humans and bacteria has enabled a better understanding of these interactions, which can inform the development of vaccines and other control measures.


Asunto(s)
Genoma Bacteriano , Mycobacterium tuberculosis , Tuberculosis , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/patogenicidad , Tuberculosis/microbiología , Tuberculosis/genética , Genómica , Variación Genética , Filogenia , Genotipo , Evolución Molecular , Filogeografía , Interacciones Huésped-Patógeno/genética
2.
Plant J ; 119(1): 404-412, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38646817

RESUMEN

The main bottleneck in the application of biotechnological breeding methods to woody species is due to the in vitro regeneration recalcitrance shown by several genotypes. On the other side, woody species, especially grapevine (Vitis vinifera L.), use most of the pesticides and other expensive inputs in agriculture, making the development of efficient approaches of genetic improvement absolutely urgent. Genome editing is an extremely promising technique particularly for wine grape genotypes, as it allows to modify the desired gene in a single step, preserving all the quality traits selected and appreciated in elite varieties. A genome editing and regeneration protocol for the production of transgene-free grapevine plants, exploiting the lipofectamine-mediated direct delivery of CRISPR-Cas9 ribonucleoproteins (RNPs) to target the phytoene desaturase gene, is reported. We focused on Nebbiolo (V. vinifera), an extremely in vitro recalcitrant wine genotype used to produce outstanding wines, such as Barolo and Barbaresco. The use of the PEG-mediated editing method available in literature and employed for highly embryogenic grapevine genotypes did not allow the proper embryo development in the recalcitrant Nebbiolo. Lipofectamines, on the contrary, did not have a negative impact on protoplast viability and plant regeneration, leading to the obtainment of fully developed edited plants after about 5 months from the transfection. Our work represents one of the first examples of lipofectamine use for delivering editing reagents in plant protoplasts. The important result achieved for the wine grape genotype breeding could be extended to other important wine grape varieties and recalcitrant woody species.


Asunto(s)
Sistemas CRISPR-Cas , Edición Génica , Genotipo , Lípidos , Protoplastos , Vitis , Vitis/genética , Edición Génica/métodos , Protoplastos/metabolismo , Ribonucleoproteínas/genética , Ribonucleoproteínas/metabolismo , Vino , Genoma de Planta/genética , Oxidorreductasas/genética , Oxidorreductasas/metabolismo
3.
Am J Hum Genet ; 109(9): 1667-1679, 2022 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-36055213

RESUMEN

African populations are the most diverse in the world yet are sorely underrepresented in medical genetics research. Here, we examine the structure of African populations using genetic and comprehensive multi-generational ethnolinguistic data from the Neuropsychiatric Genetics of African Populations-Psychosis study (NeuroGAP-Psychosis) consisting of 900 individuals from Ethiopia, Kenya, South Africa, and Uganda. We find that self-reported language classifications meaningfully tag underlying genetic variation that would be missed with consideration of geography alone, highlighting the importance of culture in shaping genetic diversity. Leveraging our uniquely rich multi-generational ethnolinguistic metadata, we track language transmission through the pedigree, observing the disappearance of several languages in our cohort as well as notable shifts in frequency over three generations. We find suggestive evidence for the rate of language transmission in matrilineal groups having been higher than that for patrilineal ones. We highlight both the diversity of variation within Africa as well as how within-Africa variation can be informative for broader variant interpretation; many variants that are rare elsewhere are common in parts of Africa. The work presented here improves the understanding of the spectrum of genetic variation in African populations and highlights the enormous and complex genetic and ethnolinguistic diversity across Africa.


Asunto(s)
Variación Genética , Genética de Población , África Austral , Población Negra/genética , Estructuras Genéticas , Variación Genética/genética , Humanos
4.
J Virol ; 98(8): e0099024, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39007617

RESUMEN

Respiratory syncytial virus (RSV) is a common cause of respiratory infection that often leads to hospitalization of infected younger children and older adults. RSV is classified into two strains, A and B, each with several subgroups or genotypes. One issue with the definition of these subgroups is the lack of a unified method of identification or genotyping. We propose that genotyping strategies based on the genes coding for replication-associated proteins could provide critical information on the replication capacity of the distinct subgroups, while clearly distinguishing genotypes. Here, we analyzed the virus replication-associated genes N, P, M2, and L from de novo assembled RSV A sequences obtained from 31 newly sequenced samples from hospitalized patients in Philadelphia and 78 additional publicly available sequences from different geographic locations within the United States. In-depth analysis and annotation of variants in the replication-associated proteins identified the polymerase protein L as a robust target for genotyping RSV subgroups. Importantly, our analysis revealed non-synonymous variations in L that were consistently accompanied by conserved changes in its co-factor P or the M2-2 protein, suggesting associations and interactions between specific domains of these proteins. Similar associations were seen among sequences of the related human metapneumovirus. These results highlight L as an alternative to other RSV genotyping targets and demonstrate the value of in-depth analyses and annotations of RSV sequences as it can serve as a foundation for subsequent in vitro and clinical studies on the efficiency of the polymerase and fitness of different virus isolates.IMPORTANCEGiven the historical heterogeneity of respiratory syncytial virus (RSV) and the disease it causes, there is a need to understand the properties of the circulating RSV strains each season. This information would benefit from an informative and consensus method of genotyping the virus. Here, we carried out a variant analysis that shows a pattern of specific variations among the replication-associated genes of RSV A across different seasons. Interestingly, these variation patterns, which were also seen in human metapneumovirus sequences, point to previously defined interactions of domains within these genes, suggesting co-variation in the replication-associated genes. Our results also suggest a genotyping strategy that can prove to be particularly important in understanding the genotype-phenotype correlation in the era of RSV vaccination, where selective pressure on the virus to evolve is anticipated. More importantly, the categorization of pneumoviruses based on these patterns may be of prognostic value.


Asunto(s)
Genotipo , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Proteínas Virales , Replicación Viral , Humanos , Virus Sincitial Respiratorio Humano/genética , Virus Sincitial Respiratorio Humano/clasificación , Infecciones por Virus Sincitial Respiratorio/virología , Replicación Viral/genética , Proteínas Virales/genética , Filogenia , Variación Genética , Lactante , Estados Unidos , Preescolar , Philadelphia
5.
J Virol ; 98(5): e0042424, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38629837

RESUMEN

Chronic hepatitis B virus (HBV) infections are strongly associated with liver cirrhosis, inflammation, and hepatocellular carcinoma. In this context, the viral HBx protein is considered as a major factor influencing HBV-associated pathogenesis through deregulation of multiple cellular signaling pathways and is therefore a potential target for prognostic and therapeutic applications. However, HBV-associated pathogenesis differs significantly between genotypes, with the relevant factors and in particular the contribution of the genetic diversity of HBx being largely unknown. To address this question, we studied the specific genotype-dependent impact of HBx on cellular signaling pathways, focusing in particular on morphological and functional parameters of mitochondria. To exclusively investigate the impact of HBx of different genotypes on integrity and function of mitochondria in the absence of additional viral factors, we overexpressed HBx in Huh7 or HepG2 cells. Key signaling pathways were profiled by kinome analysis and correlated with expression levels of mitochondrial and pathogenic markers. Conclusively, HBx of genotypes A and G caused strong disruption of mitochondrial morphology alongside an induction of PTEN-induced putative kinase 1/Parkin-mediated mitophagy. These effects were only moderately dysregulated by genotypes B and E, whereas genotypes C and D exhibit an intermediate effect in this regard. Accordingly, changes in mitochondrial membrane potential and elevated reactive oxygen species production were associated with the HBx-mediated dysfunction among different genotypes. Also, genotype-related differences in mitophagy induction were identified and indicated that HBx-mediated changes in the mitochondria morphology and function strongly depend on the genotype. This indicates a relevant role of HBx in the process of genotype-dependent liver pathogenesis of HBV infections and reveals underlying mechanisms.IMPORTANCEThe hepatitis B virus is the main cause of chronic liver disease worldwide and differs in terms of pathogenesis and clinical outcome among the different genotypes. Furthermore, the viral HBx protein is a known factor in the progression of liver injury by inducing aberrant mitochondrial structures and functions. Consequently, the selective removal of dysfunctional mitochondria is essential to maintain overall cellular homeostasis and cell survival. Consistent with the intergenotypic difference of HBV, our data reveal significant differences regarding the impact of HBx of different genotypes on mitochondrial dynamic and function and thereby on radical oxygen stress levels within the cell. We subsequently observed that the induction of mitophagy differs significantly across the heterogenetic HBx proteins. Therefore, this study provides evidence that HBx-mediated changes in the mitochondria dynamics and functionality strongly depend on the genotype of HBx. This highlights an important contribution of HBx in the process of genotype-dependent liver pathogenesis.


Asunto(s)
Virus de la Hepatitis B , Dinámicas Mitocondriales , Transducción de Señal , Transactivadores , Proteínas Reguladoras y Accesorias Virales , Humanos , Carcinoma Hepatocelular/virología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/genética , Genotipo , Células Hep G2 , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/metabolismo , Virus de la Hepatitis B/fisiología , Hepatitis B Crónica/virología , Hepatitis B Crónica/metabolismo , Hepatitis B Crónica/patología , Potencial de la Membrana Mitocondrial , Mitocondrias/metabolismo , Mitofagia , Especies Reactivas de Oxígeno/metabolismo , Transactivadores/metabolismo , Transactivadores/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Proteínas Reguladoras y Accesorias Virales/metabolismo
6.
Trends Immunol ; 43(8): 640-656, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35842266

RESUMEN

Tuberculosis (TB), the world's deadliest bacterial infection, afflicts more human males than females, with a male/female (M/F) ratio of 1.7. Sex disparities in TB prevalence, pathophysiology, and clinical manifestations are widely reported, but the underlying biological mechanisms remain largely undefined. This review assesses epidemiological data on sex disparity in TB, as well as possible underlying hormonal and genetic mechanisms that might differentially modulate innate and adaptive immune responses in males and females, leading to sex differences in disease susceptibility. We consider whether this sex disparity can be extended to the efficacy of vaccines and discuss novel animal models which may offer mechanistic insights. A better understanding of the biological factors underpinning sex-related immune responses in TB may enable sex-specific personalized therapies for TB.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis , Animales , Susceptibilidad a Enfermedades , Femenino , Humanos , Inmunidad , Masculino , Tuberculosis/genética
7.
J Infect Dis ; 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-39387651

RESUMEN

BACKGROUND: We observed a discrepancy between dengue NS1 antigen test and molecular diagnostics, with the emergence of (DENV) serotype 3 in Sri Lanka and sought to understand the cause for the rise in cases and high failure rates of molecular diagnostics. METHODS: Whole genomic sequencing was carried out in 22 DENV-3 samples. Phylogenetic and molecular clock analysis were done for genotype assignment and to understand the rate of evolution. Mutation analysis was done to understand the reasons for PCR non-detection. RESULTS: We identified two DENV-3 genotypes (I and III) co-circulating. DENV-3 genotype III strains shared a common ancestor with a sequence from India collected in 2022, while DENV-3 genotype I, was found to share a common ancestor with DENV-3 sequences from China. DENV-3 genotype III was detected by the modified CDC DENV-3 primers whereas, genotype I evaded detection due to key mutations at forward and reverse primer binding sites. We identified point mutations, C744T and A756G of the forward primer binding sites and in position G795A of the reverse primer binding sites which were not identified in DENV-3 genotype III. Furthermore, our Sri Lankan DENV-3 strains demonstrated a high root to tip ratio, compared to the previous DENV-3 sequences, indicating a high mutation rate during the points of sampling (year 2017 to 2023). CONCLUSION: The co-circulation of multiple genotypes associated with an increase in cases highlights the importance of continuous surveillance of DENVs to identify mutations resulting in non-detection by diagnostics and differences in virulence.

8.
Physiol Genomics ; 56(2): 179-193, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38047312

RESUMEN

Epigenetic alterations such as dysregulation of miRNAs have been reported to play important roles in interactions between genetic and environmental factors. In this study, we tested the hypothesis that induction of lung inflammation by inhaled allergens triggers a sex-specific miRNA regulation that is dependent on chromosome complement and hormonal milieu. We challenged the four core genotypes (FCGs) model through intranasal sensitization with a house dust mite (HDM) solution (or PBS as a control) for 5 wk. The FCG model allows four combinations of gonads and sex chromosomes: 1) XX mice with ovaries (XXF), 2) XY mice with testes (XYM), 3) XX mice with testes (XXM), and 4) XY mice with ovaries (XYF). Following the challenge (n = 5-7/group), we assessed the expression of 84 inflammatory miRNAs in lung tissue using a PCR array and cytokine levels in bronchoalveolar lavage fluid (BAL) by a multiplex protein assay (n = 4-7 animals/group). Our results showed higher levels of the chemokine KC (an Il-8 homolog) and IL-7 in BAL from XYF mice challenged with HDM. In addition, IL-17A was significantly higher in BAL from both XXF and XYF mice. A three-way interaction among treatment, gonads, and sex chromosome revealed 60 of 64 miRNAs that differed in expression depending on genotype; XXF, XXM, XYF, and XYM mice had 45, 32, 4, and 52 differentially expressed miRNAs, respectively. Regulatory networks of miRNAs identified in this study were implicated in pathways associated with asthma. Female gonadal hormonal effects may alter miRNA expression and contribute to the higher susceptibility of females to asthma.NEW & NOTEWORTHY miRNAs play important roles in regulating gene and environmental interactions. However, their role in mediating sex differences in allergic responses and lung diseases has not been elucidated. Our study used a targeted omics approach to characterize the contributions of gonadal hormones and chromosomal components to lung responses to an allergen challenge. Our results point to the influence of sex hormones in miRNA expression and proinflammatory markers in allergic airway inflammation.


Asunto(s)
Asma , MicroARNs , Femenino , Animales , Ratones , Masculino , Citocinas/genética , MicroARNs/genética , MicroARNs/metabolismo , Pulmón/metabolismo , Cromosomas Sexuales/genética , Cromosomas Sexuales/metabolismo , Asma/genética , Asma/metabolismo , Inflamación/genética , Inflamación/metabolismo , Líquido del Lavado Bronquioalveolar , Hormonas Gonadales/genética , Hormonas Gonadales/metabolismo , Modelos Animales de Enfermedad
9.
Physiol Genomics ; 56(2): 235-245, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38047309

RESUMEN

Sex differences in allergic inflammation have been reported, but the mechanisms underlying these differences remain unknown. Contributions of both sex hormones and sex-related genes to these mechanisms have been previously suggested in clinical and animal studies. Here, Four-Core Genotypes (FCG) mouse model was used to study the inflammatory response to house dust mite (HDM) challenge and identify differentially expressed genes (DEGs) and regulatory pathways in lung tissue. Briefly, adult mice (8-10 wk old) of the FCG (XXM, XXF, XYM, XYF) were challenged intranasally with 25 µg of HDM or vehicle (PBS-control group) 5 days/wk for 5 wk (n = 3/10 group). At 72 h after the last exposure, we analyzed the eosinophils and neutrophils in the bronchoalveolar lavage (BAL) of FCG mice. We extracted lung tissue and determined DEGs using Templated Oligo-Sequencing (TempO-Seq). DEG analysis was performed using the DESeq2 package and gene enrichment analysis was done using Ingenuity Pathway Analysis. A total of 2,863 DEGs were identified in the FCG. Results revealed increased eosinophilia and neutrophilia in the HDM-treated group with the most significantly expressed genes in XYF phenotype and a predominant effect of female hormones vs. chromosomes. Regardless of the sex hormones, mice with female chromosomes had more downregulated genes in the HDM group but this was reversed in the control group. Interestingly, genes associated with inflammatory responses were overrepresented in the XXM and XYF genotypes treated with HDM. Sex hormones and chromosomes contribute to inflammatory responses to HDM challenge, with female hormones exerting a predominant effect mediated by inflammatory DEGs.NEW & NOTEWORTHY Gene expression profiling helps to provide deep insight into the global view of disease-related mechanisms and responses to therapy. Using the Four-Core Genotype mouse model, our findings revealed the influence of sex hormones and sex chromosomes in the gene expression of lungs exposed to an aeroallergen (House Dust Mite) and identified sex-specific pathways to better understand sex disparities associated with allergic airway inflammation.


Asunto(s)
Alérgenos , Pulmón , Femenino , Ratones , Masculino , Animales , Alérgenos/metabolismo , Pulmón/metabolismo , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Pyroglyphidae , Inflamación/genética , Inflamación/metabolismo , Hormonas Esteroides Gonadales/metabolismo , Genotipo , Expresión Génica , Hormonas/metabolismo , Líquido del Lavado Bronquioalveolar
10.
Physiol Genomics ; 56(6): 417-425, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38640403

RESUMEN

Evidence abounds that gut microbiome components are associated with sex disparities in the immune system. However, it remains unclear whether the observed sex disparity in asthma incidence is associated with sex-dependent differences in immune-modulating gut microbiota, and/or its influence on allergic airway inflammatory processes. Using a mouse model of house dust mite (HDM)-induced allergic inflammation and the four core genotypes (FCGs) model, we have previously reported sex differences in lung inflammatory phenotypes. Here, we investigated associations of gut microbiomes with these phenotypes by challenging FCG mice [mouse with female sex chromosome and male gonad (XXM), mouse with female sex chromosome and female gonad (XXF), mouse with male sex chromosome and male gonad (XYM), and mouse with male sex chromosome and female gonad (XYF); n = 7/group] with HDM (25 µg) or PBS intranasally for 5 wk and collecting fecal samples. We extracted fecal DNA and analyzed the 16S microbiome via Targeted Metagenomic Sequencing. We compared α and ß diversity across genotypes and assessed the Firmicutes/Bacteroidetes (F/B) ratio. When comparing baseline and after exposure for the FCG, we found that the gut F/B ratio was only increased in the XXM genotype. We also found that α diversity was significantly increased in all FCG mice upon HDM challenge, with the highest increase in the XXF, and the lowest in the XXM genotypes. Similarly, ß diversity of the microbial community was also affected by challenge in a gonad- and chromosome-dependent manner. In summary, our results indicated that HDM treatment, gonads, and sex chromosomes significantly influence the gut microbial community composition. We concluded that allergic lung inflammation may be affected by the gut microbiome in a sex-dependent manner involving both hormonal and genetic influences.NEW & NOTEWORTHY Recently, the gut microbiome and its role in chronic respiratory disease have been the subject of extensive research and the establishment of its involvement in immune functions. Using the FCG mouse model, our findings revealed the influence of gonads and sex chromosomes on the microbial community structure before and after exposure to HDM. Our data provide a potential new avenue to better understand mediators of sex disparities associated with allergic airway inflammation.


Asunto(s)
Modelos Animales de Enfermedad , Microbioma Gastrointestinal , Animales , Microbioma Gastrointestinal/genética , Femenino , Masculino , Ratones , Cromosomas Sexuales/genética , Asma/inmunología , Asma/microbiología , Asma/genética , Pyroglyphidae/inmunología , Inflamación/genética , Inflamación/inmunología , Inflamación/microbiología , Genotipo , Gónadas/microbiología , Hipersensibilidad/inmunología , Hipersensibilidad/microbiología , Hipersensibilidad/genética , Caracteres Sexuales
11.
BMC Genomics ; 25(1): 64, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38229016

RESUMEN

BACKGROUND: Largemouth bass (Micropterus salmoides) has significant economic value as a high-yielding fish species in China's freshwater aquaculture industry. Determining the major genes related to growth traits and identifying molecular markers associated with these traits serve as the foundation for breeding strategies involving gene pyramiding. In this study, we screened restriction-site associated DNA sequencing (RAD-seq) data to identify single nucleotide polymorphism (SNP) loci potentially associated with extreme growth differences between fast-growth and slow-growth groups in the F1 generation of a largemouth bass population. RESULTS: We subsequently identified associations between these loci and specific candidate genes related to four key growth traits (body weight, body length, body height, and body thickness) based on SNP genotyping. In total, 4,196,486 high-quality SNPs were distributed across 23 chromosomes. Using a population-specific genotype frequency threshold of 0.7, we identified 30 potential SNPs associated with growth traits. Among the 30 SNPs, SNP19140160, SNP9639603, SNP9639605, and SNP23355498 showed significant associations; three of them (SNP9639603, SNP9639605, and SNP23355498) were significantly associated with one trait, body length, in the F1 generation, and one (SNP19140160) was significantly linked with four traits (body weight, height, length, and thickness) in the F1 generation. The markers SNP19140160 and SNP23355498 were located near two growth candidate genes, fam174b and ppip5k1b, respectively, and these candidate genes were closely linked with growth, development, and feeding. The average body weight of the group with four dominant genotypes at these SNP loci in the F1 generation population (703.86 g) was 19.63% higher than that of the group without dominant genotypes at these loci (588.36 g). CONCLUSIONS: Thus, these four markers could be used to construct a population with dominant genotypes at loci related to fast growth. These findings demonstrate how markers can be used to identify genes related to fast growth, and will be useful for molecular marker-assisted selection in the breeding of high-quality largemouth bass.


Asunto(s)
Lubina , Polimorfismo de Nucleótido Simple , Animales , Lubina/genética , Frecuencia de los Genes , Genotipo , Peso Corporal/genética
12.
Plant Cell Physiol ; 65(5): 729-736, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38288629

RESUMEN

Genome-editing tools such as the clustered regularly interspaced short palindromic repeats/Cas9 (CRISPR/Cas9) system have become essential tools for increasing the efficiency and accuracy of plant breeding. Using such genome-editing tools on maize, one of the most important cereal crops of the world, will greatly benefit the agriculture and the mankind. Conventional genome-editing methods typically used for maize involve insertion of a Cas9-guide RNA expression cassette and a selectable marker in the genome DNA; however, using such methods, it is essential to eliminate the inserted DNA cassettes to avoid legislative concerns on gene-modified organisms. Another major hurdle for establishing an efficient and broadly applicable DNA-free genome-editing system for maize is presented by recalcitrant genotypes/cultivars, since cell/tissue culture and its subsequent regeneration into plantlets are crucial for producing transgenic and/or genome-edited maize. In this study, to establish a DNA-free genome-editing system for recalcitrant maize genotypes/cultivars, Cas9-gRNA ribonucleoproteins were directly delivered into zygotes isolated from the pollinated flowers of the maize-B73 cultivar. The zygotes successfully developed and were regenerated into genome-edited plantlets by co-culture with phytosulfokine, a peptide phytohormone. The method developed herein made it possible to obtain DNA- and selectable-marker-free genome-edited recalcitrant maize genotypes/cultivars with high efficiency. This method can advance the molecular breeding of maize and other important cereals, regardless of their recalcitrant characteristics.


Asunto(s)
Sistemas CRISPR-Cas , Edición Génica , Genoma de Planta , Zea mays , Zea mays/genética , Edición Génica/métodos , Plantas Modificadas Genéticamente , Cigoto/metabolismo , Fitomejoramiento/métodos , ARN Guía de Sistemas CRISPR-Cas/genética , ADN de Plantas/genética
13.
Clin Gastroenterol Hepatol ; 22(5): 1024-1036.e2, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38145725

RESUMEN

BACKGROUND & AIMS: PNPLA3 G-allele is an important determinant of disease severity in nonalcoholic fatty liver disease (NAFLD). Here, we investigated the effect of age, body mass index (BMI), and type 2 diabetes mellitus (T2DM) on the relationship between PNPLA3 G-allele and advanced fibrosis in adults and children with histologically characterized NAFLD. METHODS: A total of 1047 children and 2057 adults were included. DNA was genotyped for rs738409 in duplicate. Primary outcome of interest was advanced fibrosis (fibrosis stage ≥3). Regression analyses were performed after controlling for relevant covariates. An additive model was used to assess the effect of PNPLA3 G-allele (CC vs CG vs GG). RESULTS: PNPLA3 G-allele was significantly associated with advanced fibrosis in children (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.16-2.09) and adults (OR, 1.55; 95% CI, 1.16-1.54). Across the cohort, older age significantly increased the risk for advanced fibrosis for PNPLA3 CC (OR, 1.019; 95% CI, 1.013-1.026), CG (OR, 1.024; 95% CI, 1.018-1.030), and GG (OR, 1.03; 95% CI, 1.023-1.037) genotypes. BMI significantly increased the relationship between PNPLA3 genotypes and advanced fibrosis in children and adults. A BMI of 30 kg/m2 was the cutoff beyond which PNPLA3 G-allele had exponential effect on the risk for advanced fibrosis in children and adults. T2DM significantly worsened the relationship between PNPLA3 G-allele and advanced fibrosis in children and adults (interaction P < .01 for both). CONCLUSIONS: Age, BMI, and T2DM modify the risk of advanced fibrosis associated with PNPLA3 G-allele. Preventing or reversing T2DM and obesity in persons carrying PNPLA3 G-allele may lower the risk for advanced fibrosis in NAFLD.


Asunto(s)
Aciltransferasas , Índice de Masa Corporal , Diabetes Mellitus Tipo 2 , Lipasa , Cirrosis Hepática , Proteínas de la Membrana , Enfermedad del Hígado Graso no Alcohólico , Fosfolipasas A2 Calcio-Independiente , Humanos , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/patología , Lipasa/genética , Proteínas de la Membrana/genética , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Masculino , Adulto , Niño , Persona de Mediana Edad , Adolescente , Factores de Edad , Cirrosis Hepática/genética , Adulto Joven , Anciano , Genotipo , Predisposición Genética a la Enfermedad
14.
BMC Plant Biol ; 24(1): 856, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39266950

RESUMEN

BACKGROUND: The frequency and severity of abiotic stress events, especially drought, are increasing due to climate change. The plant root is the most important organ for water uptake and the first to be affected by water limitation. It is therefore becoming increasingly important to include root traits in studies on drought stress tolerance. However, phenotyping under field conditions remains a challenging task. In this study, plants were grown in a hydroponic system with polyethylene glycol as an osmotic stressor and in sand pots to examine the root system of eleven spring barley genotypes. The root anatomy of two genotypes with different response to drought was investigated microscopically. RESULTS: Root diameter increased significantly (p < 0.05) under polyethylene glycol treatment by 54% but decreased significantly (p < 0.05) by 12% under drought stress in sand pots. Polyethylene glycol treatment increased root tip diameter (51%) and reduced diameter of the elongation zone (14%) compared to the control. Under drought stress, shoot mass of plants grown in sand pots showed a higher correlation (r = 0.30) with the shoot mass under field condition than polyethylene glycol treated plants (r = -0.22). CONCLUSION: These results indicate that barley roots take up polyethylene glycol by the root tip and polyethylene glycol prevents further water uptake. Polyethylene glycol-triggered osmotic stress is therefore unsuitable for investigating root morphology traits in barley. Root architecture of roots grown in sand pots is more comparable to roots grown under field conditions.


Asunto(s)
Hordeum , Raíces de Plantas , Polietilenglicoles , Hordeum/efectos de los fármacos , Hordeum/anatomía & histología , Hordeum/crecimiento & desarrollo , Hordeum/fisiología , Hordeum/genética , Raíces de Plantas/anatomía & histología , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/crecimiento & desarrollo , Polietilenglicoles/farmacología , Sequías , Genotipo , Estrés Fisiológico
15.
BMC Plant Biol ; 24(1): 576, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38890568

RESUMEN

BACKGROUND: Little leaf disease caused by phytoplasma infection is a significant threat to eggplant (also known as brinjal) cultivation in India. This study focused on the molecular characterisation of the phytoplasma strains and insect vectors responsible for its transmission and screening of brinjal germplasm for resistance to little leaf disease. RESULTS: Surveys conducted across districts in the Tamil Nadu state of India during 2021-2022 showed a higher incidence of phytoplasma during the Zaid (March to June), followed by Kharif (June to November) and Rabi (November to March) seasons with mean incidence ranging from 22 to 27%. As the name indicates, phytoplasma infection results in little leaf (reduction in leaf size), excessive growth of axillary shoots, virescence, phyllody, stunted growth, leaf chlorosis and witches' broom symptoms. PCR amplification with phytoplasma-specific primers confirmed the presence of this pathogen in all symptomatic brinjal plants and in Hishimonus phycitis (leafhopper), providing valuable insights into the role of leafhoppers in disease transmission. BLAST search and phylogenetic analysis revealed the phytoplasma strain as "Candidatus Phytoplasma trifolii". Insect population and disease dynamics are highly influenced by environmental factors such as temperature, relative humidity and rainfall. Further, the evaluation of 22 eggplant accessions revealed immune to highly susceptible responses where over 50% of the entries were highly susceptible. Finally, additive main effect and multiplicative interaction (AMMI) and won-where biplot analyses identified G18 as a best-performing accession for little leaf resistance due to its consistent responses across multiple environments. CONCLUSIONS: This research contributes essential information on little leaf incidence, symptoms, transmission and resistance profiles of different brinjal genotypes, which together ensure effective and sustainable management of this important disease of eggplants.


Asunto(s)
Resistencia a la Enfermedad , Phytoplasma , Enfermedades de las Plantas , Hojas de la Planta , Solanum melongena , Solanum melongena/microbiología , Solanum melongena/genética , Enfermedades de las Plantas/microbiología , Phytoplasma/fisiología , Resistencia a la Enfermedad/genética , Hojas de la Planta/microbiología , India , Filogenia , Animales , Hemípteros/microbiología , Incidencia , Insectos Vectores/microbiología
16.
BMC Plant Biol ; 24(1): 713, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39060959

RESUMEN

Rice (Oryza sativa L.) is an essential food for half of the global population and is vital in maintaining global food security. Climate change, increasing population and recent incident of COVID pandemic has generated financial burden and threaten the global food security. Due to theses factors rice cultivation also has to face significant challenges. frequent weather changes pose a considerable challenge to agricultural planning, which was previously relaying on consistent seasonal variations. In this context, rice cultivation is particularly sensitive to cold, where its development and productivity inhibited by low temperatures (< 18 °C). Developing rice varietes with low temprature tolerence and good yield potential is one of the major goals of current breeding efforts of plant scientists. For this purpose, short duration and early rice varieties are most favorable to avoid cold stress and yield more in less number of days. this study was designed to investigate the effect of low temperatures on different rice varieties. the study was designed to identify low temprature tolerent genotypes with early and regular cultivation. For this, thirty-four genotypes were evaluated in two gorwing seasons (2018-2019) with four different sowing times. Statistically sowing time showed significant interaction between all yield contributing parameters. The data indicate that exposure to low temperatures during the reproductive phase prolongs the maturation period of the crop, also length of the panicle and the fertility of the spikelets drops, resulting in a significant decrease in the production of sensitive varieties. Some varieties are more sensitive to cold stress compared to others. In the Egyptian context, Giza176, Sakha104, and Sakha107 are recommended for early cultivation, while the genotypes Giza 179, Sakha101, Sakha104, and GZ 9730-1-1-1-1 are indicated for the normal cultivation period. The Sakha104 variety is particularly notable, as it is recommended for both purposes. In addition, the data obtained in this study provide valuable information for selecting rice varieties suitable for double cropping in the North Delta of Egypt. This study also contributes to the existing literature, providing insights into the resilience of rice cultivation in the face of climate change.


Asunto(s)
Respuesta al Choque por Frío , Genotipo , Oryza , Oryza/genética , Oryza/crecimiento & desarrollo , Respuesta al Choque por Frío/genética , Frío , Factores de Tiempo , Estaciones del Año
17.
BMC Plant Biol ; 24(1): 238, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38566027

RESUMEN

BACKGROUND: The fruity aromatic bouquet of coffee has attracted recent interest to differentiate high value market produce as specialty coffee. Although the volatile compounds present in green and roasted coffee beans have been extensively described, no study has yet linked varietal molecular differences to the greater abundance of specific substances and support the aroma specificity of specialty coffees. RESULTS: This study compared four Arabica genotypes including one, Geisha Especial, suggested to generate specialty coffee. Formal sensory evaluations of coffee beverages stressed the importance of coffee genotype in aroma perception and that Geisha Especial-made coffee stood out by having fine fruity, and floral, aromas and a more balanced acidity. Comparative SPME-GC-MS analyses of green and roasted bean volatile compounds indicated that those of Geisha Especial differed by having greater amounts of limonene and 3-methylbutanoic acid in agreement with the coffee cup aroma perception. A search for gene ontology differences of ripening beans transcriptomes of the four varieties revealed that they differed by metabolic processes linked to terpene biosynthesis due to the greater gene expression of prenyl-pyrophosphate biosynthetic genes and terpene synthases. Only one terpene synthase (CaTPS10-like) had an expression pattern that paralleled limonene loss during the final stage of berry ripening and limonene content in the studied four varieties beans. Its functional expression in tobacco leaves confirmed its functioning as a limonene synthase. CONCLUSIONS: Taken together, these data indicate that coffee variety genotypic specificities may influence ripe berry chemotype and final coffee aroma unicity. For the specialty coffee variety Geisha Especial, greater expression of terpene biosynthetic genes including CaTPS10-like, a limonene synthase, resulted in the greater abundance of limonene in green beans, roasted beans and a unique citrus note of the coffee drink.


Asunto(s)
Transferasas Alquil y Aril , Coffea , Liasas Intramoleculares , Odorantes , Coffea/genética , Limoneno , Terpenos , Semillas , Perfilación de la Expresión Génica
18.
Planta ; 259(5): 105, 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38551685

RESUMEN

MAIN CONCLUSION: Monoterpenes and phenolics play distinct roles in defending white spruce trees from insect defoliators. Monoterpenes contribute to the toxicity of the foliage, deterring herbivory, whereas phenolics impede budworm growth. This study demonstrates the complex interplay between monoterpenes and phenolics and their collective influence on the defense strategy of white spruce trees against a common insect defoliator. Long-lived coniferous trees display considerable variations in their defensive chemistry. The impact of these defense phenotype variations on insect herbivores of the same species remains to be thoroughly studied, mainly due to challenges in replicating the comprehensive defense profiles of trees under controlled conditions. This study methodically examined the defensive properties of foliar monoterpenes and phenolics across 80 distinct white spruce families. These families were subsequently grouped into two chemotypes based on their foliar monoterpene concentrations. To understand the separate and combined effects of these classes on tree defenses to the eastern spruce budworm, we conducted feeding experiments using actual defense profiles from representative families. Specifically, we assessed budworm response when exposed to substrates amended with phenolics alone or monoterpenes. Our findings indicate that the ratios and amounts of monoterpenes and phenolics present in the white spruce foliage influence the survival of spruce budworms. Phenotypes associated with complete larval mortality exhibited elevated ratios (ranging from 0.4 to 0.6) and concentrations (ranging from 1143 to 1796 ng mg-1) of monoterpenes. Conversely, families characterized by higher phenolic ratios (ranging from 0.62 to 0.77) and lower monoterpene concentrations (ranging from 419 to 985 ng mg-1) were less lethal to the spruce budworm. Both classes of defense compounds contribute significantly to the overall defensive capabilities of white spruce trees. Monoterpenes appear critical in determining the general toxicity of foliage, while phenolics play a role in slowing budworm development, thereby underscoring their collective importance in white spruce defenses.


Asunto(s)
Mariposas Nocturnas , Picea , Animales , Picea/genética , Mariposas Nocturnas/fisiología , Larva/fisiología , Monoterpenos , Árboles , Fenoles
19.
J Virol ; 97(3): e0147222, 2023 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-36815771

RESUMEN

Respiratory syncytial virus (RSV) has a significant health burden in children, older adults, and the immunocompromised. However, limited effort has been made to identify emergence of new RSV genotypes' frequency of infection and how the combination of nasopharyngeal microbiome and viral genotypes impact RSV disease outcomes. In an observational cohort designed to capture the first infant RSV infection, we employed multi-omics approaches to sequence 349 RSV complete genomes and matched nasopharyngeal microbiomes, during which the 2012/2013 season was dominated by RSV-A, whereas 2013 and 2014 was dominated by RSV-B. We found non-G-72nt-duplicated RSV-A strains were more frequent in male infants (P = 0.02), whereas G-72nt-duplicated genotypes (which is ON1 lineage) were seen equally in both males and females. DESeq2 testing of the nasal microbiome showed Haemophilus was significantly more abundant in infants with RSV-A infection compared to infants with RSV-B infection (adjusted P = 0.002). In addition, the broad microbial clustering of the abundant genera was significantly associated with infant sex (P = 0.03). Overall, we show sex differences in infection by RSV genotype and host nasopharyngeal microbiome, suggesting an interaction between host genetics, virus genotype, and associated nasopharyngeal microbiome. IMPORTANCE Respiratory syncytial virus (RSV) is one of the leading causes of lower respiratory tract infections in young children and is responsible for high hospitalization rates and morbidity in infants and the elderly. To understand how the emergence of RSV viral genotypes and viral-respiratory microbiome interactions contribute to infection frequency and severity, we utilized an observational cohort designed to capture the first infant RSV infection we employed multi-omics approaches to sequence 349 RSV complete genomes and matched nasopharyngeal microbiomes. We found non-G-72nt-duplicated RSV-A genotypes were more frequent in male infants, whereas G-72nt-duplicated RSV-A strains (ON1 lineage) were seen equally in both males and females. Microbiome analysis show Haemophilus was significantly more abundant in infants with RSV-A compared to infants with RSV-B infection and the microbial clustering of the abundant genera was associated with infant sex. Overall, we show sex differences in RSV genotype-nasopharyngeal microbiome, suggesting an interaction host genetics-virus-microbiome interaction.


Asunto(s)
Interacciones Microbiota-Huesped , Microbiota , Nasofaringe , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Femenino , Humanos , Lactante , Masculino , Genotipo , Microbiota/genética , Infecciones por Virus Sincitial Respiratorio/epidemiología , Virus Sincitial Respiratorio Humano/genética , Factores Sexuales , Nasofaringe/microbiología , Interacciones Microbiota-Huesped/fisiología
20.
J Viral Hepat ; 31(11): 775-779, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39135466

RESUMEN

The prevalence of mixed hepatitis C virus (HCV) genotype infection in a representative Canadian HCV cohort is reported and virological response with direct acting antiviral (DAA) treatment was evaluated. 3272 HCV-positive participants were enrolled, of which 2945 (90.0%) initiated DAA therapy. 0.8% were identified with mixed genotype infection. Overall sustained virological response (SVR) was 99.1% and did not differ based on mixed genotype status. Any historical disadvantage to achieving cure with HCV treatment in mixed genotype infection has been overcome by current DAA regimens.


Asunto(s)
Antivirales , Genotipo , Hepacivirus , Hepatitis C Crónica , Respuesta Virológica Sostenida , Humanos , Antivirales/uso terapéutico , Antivirales/farmacología , Hepacivirus/genética , Hepacivirus/efectos de los fármacos , Hepacivirus/clasificación , Masculino , Femenino , Persona de Mediana Edad , Canadá/epidemiología , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , Resultado del Tratamiento , Adulto , Anciano , Coinfección/tratamiento farmacológico , Coinfección/virología , Prevalencia , Estudios de Cohortes
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