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Arrhythmogenic right ventricular cardiomyopathy caused by a homozygous frameshift variant (c.2358delA) in DSG2.
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Displasia Arritmogênica Ventricular Direita , Humanos , Displasia Arritmogênica Ventricular Direita/genética , Desmogleína 2/genética , Linhagem , Homozigoto , Mutação da Fase de Leitura/genéticaRESUMO
Bio-fortification is a new, viable, cost-effective, and long-term method of administering crucial minerals to a populace with limited exposure to diversified foods and other nutritional regimens. Nanotechnology entities aid in the improvement of traditional nutraceutical absorption, digestibility, and bio-availability. Nano-applications are employed in poultry systems utilizing readily accessible instruments and processes that have no negative impact on animal health and welfare. Nanotechnology is a sophisticated innovation in the realm of biomedical engineering that is used to diagnose and cure various poultry ailments. In the 21st century, zinc nanoparticles had received a lot of considerable interest due to their unusual features. ZnO NPs exhibit antibacterial properties; however, the qualities of nanoparticles (NPs) vary with their size and structure, rendering them adaptable to diverse uses. ZnO NPs have shown remarkable promise in bio-imaging and drug delivery due to their high bio-compatibility. The green synthesized nanoparticles have robust biological activities and are used in a variety of biological applications across industries. The current review also discusses the formulation and recent advancements of zinc oxide nanoparticles from plant sources (such as leaves, stems, bark, roots, rhizomes, fruits, flowers, and seeds) and their anti-cancerous activities, activities in wound healing, and drug delivery, followed by a detailed discussion of their mechanisms of action.
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Nanopartículas Metálicas , Óxido de Zinco , Animais , Zinco , Óxido de Zinco/química , Nanopartículas Metálicas/química , Aves Domésticas , Extratos Vegetais/química , Antibacterianos/químicaRESUMO
To date, several transcriptomic studies during fruit development have been reported; however, no comprehensive integrated study on expression diversity, alternative splicing, and metabolomic profiling was reported in Capsicum. This study analyzed RNA-seq data and untargeted metabolomic profiling from early green (EG), mature green (MG), and breaker (Br) fruit stages from two Capsicum species, i.e., C. annuum (Cann) and C. frutescens (Cfrut) from Northeast India. A total of 117,416 and 96,802 alternatively spliced events (AltSpli-events) were identified from Cann and Cfrut, respectively. Among AltSpli-events, intron retention (IR; 32.2% Cann and 25.75% Cfrut) followed by alternative acceptor (AA; 15.4% Cann and 18.9% Cfrut) were the most abundant in Capsicum. Around 7600 genes expressed in at least one fruit stage of Cann and Cfrut were AltSpli. The study identified spliced variants of genes including transcription factors (TFs) potentially involved in fruit development/ripening (Aux/IAA 16-like, ETR, SGR1, ARF, CaGLK2, ETR, CaAGL1, MADS-RIN, FUL1, SEPALLATA1), carotenoid (PDS, CA1, CCD4, NCED3, xanthoxin dehydrogenase, CaERF82, CabHLH100, CaMYB3R-1, SGR1, CaWRKY28, CaWRKY48, CaWRKY54), and capsaicinoids or flavonoid biosynthesis (CaMYB48, CaWRKY51), which were significantly differentially spliced (DS) between consecutive Capsicum fruit stages. Also, this study observed that differentially expressed isoforms (DEiso) from 38 genes with differentially spliced events (DSE) were significantly enriched in various metabolic pathways such as starch and sucrose metabolism, amino acid metabolism, cysteine cutin suberin and wax biosynthesis, and carotenoid biosynthesis. Furthermore, the metabolomic profiling revealed that metabolites from aforementioned pathways such as carbohydrates (mainly sugars such as D-fructose, D-galactose, maltose, and sucrose), organic acids (carboxylic acids), and peptide groups significantly altered during fruit development. Taken together, our findings could help in alternative splicing-based targeted studies of candidate genes involved in fruit development and ripening in Capsicum crop.
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Capsicum , Capsicum/genética , Capsicum/química , Capsicum/metabolismo , Frutas/genética , Carotenoides/metabolismo , Transcriptoma , Sacarose/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
Hereditary neurological disorders (HNDs) are a clinically and genetically heterogeneous group of disorders. These disorders arise from the impaired function of the central or peripheral nervous system due to aberrant electrical impulses. More than 600 various neurological disorders, exhibiting a wide spectrum of overlapping clinical presentations depending on the organ(s) involved, have been documented. Owing to this clinical heterogeneity, diagnosing these disorders has been a challenge for both clinicians and geneticists and a large number of patients are either misdiagnosed or remain entirely undiagnosed. Contribution of genetics to neurological disorders has been recognized since long; however, the complete picture of the underlying molecular bases are under-explored. The aim of this study was to accurately diagnose 11 unrelated Pakistani families with various HNDs deploying NGS as a first step approach. Using exome sequencing and gene panel sequencing, we successfully identified disease-causing genomic variants these families. We report four novel variants, one each in, ECEL1, NALCN, TBR1 and PIGP in four of the pedigrees. In the rest of the seven families, we found five previously reported pathogenic variants in POGZ, FA2H, PLA2G6 and CYP27A1. Of these, three families segregate a homozygous 18 bp in-frame deletion of FA2H, indicating a likely founder mutation segregating in Pakistani population. Genotyping for this mutation can help low-cost population wide screening in the corresponding regions of the country. Our findings not only expand the existing repertoire of mutational spectrum underlying neurological disorders but will also help in genetic testing of individuals with HNDs in other populations.
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Doenças do Sistema Nervoso , Humanos , Linhagem , Sequenciamento do Exoma , Homozigoto , Mutação , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/genética , Metaloendopeptidases , TransposasesRESUMO
Air pollution is associated with several severe physical, behavioral, and psychological health risks and glitches. Air pollution has been linked to 11 million premature deaths in Pakistan, out of the total 153 million premature deaths worldwide. Air pollution is continuously growing as a threatening challenge for Pakistan. Keeping this in view, the current study was designed to assess air pollution in terms of air quality index (AQI), particulate matters (PM2.5 and PM10), SO2, NO2, and O3 over six districts of Malakand division, Northern Pakistan. The second part of the study appraised the associated self-reported effects of air pollution on Pakistani students and the practices, perceptions, and awareness of the students regarding air pollution through a closed-ended questionnaire, administered to 4100 students. The first section of the questionnaire was focused on the physical effects associated with air pollution; the second section was focused on air pollution-linked behavior and psychology; the third portion was focused on perception and awareness of the subjects, whereas the final section was focused on practices and concerns of the subjects regarding air pollution. The students reported that exposure to air pollution significantly affected their physical health, behavior, and psychology. The subjects were aware of the different air pollutants and health complications associated with air pollution, and therefore had adopted preventive measures. It was concluded that air pollution had adverse impacts on the physical and psychological health of the respondents, which consequently altered their behavior. Mass awareness, proper mitigating plan, suitable management, and implementation of strict environmental laws are suggested before the air gets further polluted and becomes life-threatening.
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Poluição do Ar , Monitoramento Ambiental , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Humanos , Paquistão , Autorrelato , EstudantesRESUMO
Apart from using traditionally in culinary preparations, chili peppers are also important constituents of herbal medicines. Although the bioactive components are studied mostly in the fruits of Capsicum annuum, no such study reports till date is available for Ghost chili (C. chinense) from North East India. Therefore, the aim of this study was to carry out an analysis of the bioactive constituents in the naturally occurring hottest chili Ghost chili (C. chinense), and evaluate its antioxidant, pro/anti-genotoxic, and apoptotic effects in in vitro and in vivo models. Three different antioxidant assays showed that lower doses of Ghost chili extract showed higher DNA protective and antioxidant activities. Furthermore, the administration for 7 alternate days into 6 week old Swiss albino mice showed that the lower doses (50 and 100 mg/kg bw) reduced DMBA induced genotoxicity beside significantly enhancing the activities of hepatic antioxidant enzymes, while higher dose (200 mg/kg bw) induced genotoxic effect in bone marrow cells. The administration of higher dose (200 mg/kg bw) also induced apoptosis and upregulation of Bax (pro) and downregulation of Bcl-2 (anti) apoptotic genes. Dose dependent increase of apoptosis was also observed in Hep G2 and Hep 3B liver cancer cell lines. Our findings in the present study suggest that low doses of C. chinense can exert cancer chemopreventive effects. The induction of apoptosis in both cancer cell lines and mouse bone marrow cells, and up-regulation of proapoptotic genes suggests that the higher dose of C. chinense can be used for targeted cancer therapy.
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Antioxidantes/administração & dosagem , Apoptose/efeitos dos fármacos , Capsicum/química , Extratos Vegetais/administração & dosagem , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/toxicidade , Antioxidantes/farmacologia , Antioxidantes/toxicidade , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/patologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Testes de Mutagenicidade , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidadeRESUMO
The molecular mechanism of the underlying genes involved in the process of fruit ripening in Capsicum (family Solanaceae) is not clearly known. In the present study, we identified orthologs of 32 fruit development/ripening genes of tomato in Capsicum, and validated their expression in fruit development stages in C. annuum, C. frutescens, and C. chinense. In silico expression analysis using transcriptome data identified a total of 12 out of 32 genes showing differential expression during different stages of fruit development in Capsicum. Real time expression identified gene LOC107847473 (ortholog of MADS-RIN) had substantially higher expression (>500 folds) in breaker and mature fruits, which suggested the non-climacteric ripening behaviour of Capsicum. However, differential expression of Ehtylene receptor 2-like (LOC107873245) gene during fruit maturity supported the climacteric behaviour of only C. frutescens (hot pepper). Furthermore, development of 49 gene based simple sequence repeat (SSR) markers would help in selection of identified genes in Capsicum breeding.
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Capsicum/fisiologia , Frutas/fisiologia , Genes de Plantas , Marcadores Genéticos , Simulação por Computador , Frutas/genética , Regulação da Expressão Gênica de Plantas , Variação Genética , Genoma de Planta , Solanum lycopersicum/genética , Repetições de Microssatélites , Proteínas de Plantas/genética , Reprodutibilidade dos TestesRESUMO
Intellectual disability (ID) or Mental Retardation (MR) is a broad term, which occupies several medical directions. It is extremely heterogeneous and has about reported 25,000 genes of which half of the genes expression have been found in the brain. Intellectual disability causes severe disability and has a worldwide prevalence of around 2% while autosomal recessive form of ID causes almost 25% of all non syndromic (NS) ID cases. A consanguineous family (who will be referred as) MR7 with phenotype of ID was sampled in Swat region of Pakistan. All affected individuals in the family were observed having a low IQ and cognitive mutilation with no sign of biochemical, skeletal or neurological abnormalities. Their dc-ribonucleic acid (DNA) was extracted and subjected to STS (Single tagged sequence) marker analyses which showed exclusion of all known non syndromic autosomal recessive (NS-AR) ID genes. In the family MR7, autozygosity mapping was performed by microarray single-nucleotide polymorphism analysis in all the collected samples, for a close examination of the homozygous region in all the affected however no homozygosity was observed for the normal parent. In this consanguineous family of Pakistan, autozygosity mapping showed linkage interval (chr14: 30,294,526- 32,106,658) overlapping with already reported MRT9 locus (chr14:26,578,608-32,780,288) for NS- ARID.
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Mapeamento Cromossômico , Consanguinidade , Deficiência Intelectual/genética , Feminino , Marcadores Genéticos/genética , Humanos , Masculino , Repetições de Microssatélites/genética , Paquistão , Linhagem , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Autosomal recessive primary microcephaly (MCPH) is characterized by a substantial reduction in brain size but with normal architecture. It is often linked to mutations in genes coding for centrosomal proteins; however, their role in brain size regulation is not completely understood. By combining homozygosity mapping and whole-exome sequencing in an MCPH family from Pakistan, we identified a novel mutation (XM_011518861.1; c.4114C > T) in CDK5RAP2, the gene associated with primary microcephaly-3 (MCPH3), leading to a premature stop codon (p.Arg1372*). CDK5RAP2 is a component of the pericentriolar material important for the microtubule-organizing function of the centrosome. Patient-derived primary fibroblasts had strongly decreased CDK5RAP2 amounts, showed centrosomal and nuclear abnormalities and exhibited changes in cell size and migration. We further identified an interaction of CDK5RAP2 with the Hippo pathway components MST1 kinase and the transcriptional regulator TAZ. This finding potentially provides a mechanism through which the Hippo pathway with its roles in the regulation of centrosome number is linked to the centrosome. In the patient fibroblasts, we observed higher levels of TAZ and YAP. However, common target genes of the Hippo pathway were downregulated as compared to the control with the exception of BIRC5 (Survivin), which was significantly upregulated. We propose that the centrosomal deficiencies and the altered cellular properties in the patient fibroblasts can also result from the observed changes in the Hippo pathway components which could thus be relevant for MCPH and play a role in brain size regulation and development.
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Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Microcefalia/genética , Microcefalia/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Transdução de Sinais , Aciltransferases , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Encéfalo/fisiologia , Proteínas de Ciclo Celular , Movimento Celular , Tamanho Celular , Células Cultivadas , Centrossomo/ultraestrutura , Códon sem Sentido , DNA/genética , Fibroblastos/metabolismo , Ligação Genética , Predisposição Genética para Doença , Genoma Humano , Células HEK293 , Células HeLa , Fator de Crescimento de Hepatócito/metabolismo , Homozigoto , Humanos , Mutação , Tamanho do Órgão , Linhagem , Fosfoproteínas/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Fatores de Transcrição/metabolismo , Proteínas de Sinalização YAPRESUMO
Autosomal recessive primary microcephaly (MCPH) is characterized by reduced head circumference, reduction in the size of the cerebral cortex with otherwise grossly normal brain structure and variable intellectual disability. MCPH is caused by mutations of 11 different genes which code for proteins implicated in cell division and cell cycle regulation. We studied a consanguineous eight-generation family from Pakistan with ten microcephalic children using homozygosity mapping and found a new MCPH locus at HSA 7q21.11-q21.3. Sanger sequencing of the most relevant candidate genes in this region revealed a homozygous single nucleotide substitution c.589G>A in CDK6, which encodes cyclin-dependent kinase 6. The mutation changes a highly conserved alanine at position 197 into threonine (p.Ala197Thr). Post hoc whole-exome sequencing corroborated this mutation's identification as the causal variant. CDK6 is an important protein for the control of the cell cycle and differentiation of various cell types. We show here for the first time that CDK6 associates with the centrosome during mitosis; however, this was not observed in patient fibroblasts. Moreover, the mutant primary fibroblasts exhibited supernumerary centrosomes, disorganized microtubules and mitotic spindles, an increased centrosome nucleus distance, reduced cell proliferation and impaired cell motility and polarity. Upon ectopic expression of the mutant protein and knockdown of CDK6 through shRNA, we noted similar effects. We propose that the identified CDK6 mutation leads to reduced cell proliferation and impairs the correct functioning of the centrosome in microtubule organization and its positioning near the nucleus which are key determinants during neurogenesis.
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Centrossomo/metabolismo , Quinase 6 Dependente de Ciclina/genética , Deficiência Intelectual/genética , Microcefalia/genética , Mitose/genética , Mapeamento Cromossômico , Cromossomos Humanos Par 7/genética , Quinase 6 Dependente de Ciclina/química , Quinase 6 Dependente de Ciclina/metabolismo , Feminino , Estudos de Associação Genética , Humanos , Deficiência Intelectual/fisiopatologia , Masculino , Microcefalia/fisiopatologia , Microtúbulos/genética , Microtúbulos/metabolismo , Mutação , Linhagem , Polimorfismo de Nucleotídeo Único , Conformação ProteicaRESUMO
Autosomal-recessive primary microcephaly (MCPH) is a rare congenital disorder characterized by intellectual disability, reduced brain and head size, but usually without defects in cerebral cortical architecture, and other syndromic abnormalities. MCPH is heterogeneous. The underlying genes of the seven known loci code for centrosomal proteins. We studied a family from northern Pakistan with two microcephalic children using homozygosity mapping and found suggestive linkage for regions on chromosomes 2, 4, and 9. We sequenced two positional candidate genes and identified a homozygous frameshift mutation in the gene encoding the 135 kDa centrosomal protein (CEP135), located in the linkage interval on chromosome 4, in both affected children. Post hoc whole-exome sequencing corroborated this mutation's identification as the causal variant. Fibroblasts obtained from one of the patients showed multiple and fragmented centrosomes, disorganized microtubules, and reduced growth rate. Similar effects were reported after knockdown of CEP135 through RNA interference; we could provoke them also by ectopic overexpression of the mutant protein. Our findings suggest an additional locus for MCPH at HSA 4q12 (MCPH8), further strengthen the role of centrosomes in the development of MCPH, and place CEP135 among the essential components of this important organelle in particular for a normal neurogenesis.
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Proteínas de Transporte/genética , Deficiência Intelectual/genética , Microcefalia/genética , Mutação , Proteínas de Transporte/metabolismo , Centrossomo , Criança , Cromossomos Humanos Par 4/genética , Cromossomos Humanos Par 4/metabolismo , Exoma , Éxons , Feminino , Técnicas de Silenciamento de Genes , Ligação Genética , Loci Gênicos , Homozigoto , Humanos , Deficiência Intelectual/fisiopatologia , Masculino , Microcefalia/fisiopatologia , Paquistão/epidemiologia , Linhagem , Polimorfismo de Nucleotídeo Único , Interferência de RNA , Análise de Sequência de DNARESUMO
The convergence of nanotechnology with bioinformatics and the study of plant secondary metabolites hold remarkable potential for transformative scientific breakthroughs. Synergy enables a deeper understanding of the biosynthesis and functions of plant secondary metabolites, unlocking avenues to engineer novel applications in areas like pharmaceuticals, agriculture, and sustainable materials. The present study was conducted to check the effect of plant-mediated selenium nanoparticles to improve the bioactive compounds in sesame. Three varieties of sesame (TS-5, TH-6, and Till-18) were sown and got treated with different concentration of selenium nanoparticles. On the basis of antioxidant, biochemical, and physiological parameters, best performing seed samples from crop were selected and subjected to UHPLC analysis. From all 276 identified metabolites, the top 20 differentially expressed bioactive, medicinally important compounds were subjected to Swiss target prediction, KEGG, and Metascape analysis to reveal drug targets, gene targets, cell targets, and disease targets. Swiss target prediction revealed that most of the drug targets had kinases as the highest target in all the bioactive metabolites, followed by nuclear transporters, cytochrome P450, and proteins associated with electrochemical channels. Metascape analysis revealed that most of the compounds had highest enrichment in non-canonical activation of NOTCH3 followed by regulation of hormone levels. Furthermore, DisGeNET analysis revealed that most of the metabolites had strong association with impaired glucose tolerance followed by myocardial ischemia and neuralgia. Tissue and cell accumulation analysis by PaGeneBase revealed the highest accumulation in the small intestine, colon, ovary, and DRG cells. The study concluded that selenium nanoparticles has an ability to improve certain medicinally important metabolites in sesame, coupled with bioinformatics tools which revealed a great insight into the potential of those compounds, and the information can further be used in future studies.
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Sesame (Sesamum indicum) is abundant in a diverse range of lignans, including sesamin, and γ-tocopherol, constituting a cluster of bioactive phenolic compound used for food and medicinal purposes. Cardiovascular diseases remain a leading global health challenge, demanding vigilant prevention and innovative treatments. This study was carried out to evaluate the effect of plant mediated SeNPs on sesame metabolic profile and to screen and check the effect bioactive compounds against CVD via molecular drug docking technique. Three sesame germplasms TS-5, TH-6 and Till-18 were treated with varying concentrations (10, 20, 30, 40 and 50 ppm) of plant-mediated selenium nanoparticles (SeNPs). There were three groups of treatments group-1 got only seed pretreatments of SeNPs, Group-2 with only foliar applications of SeNPs and Group-3 with both seed pretreatments and foliar applications of SeNPs. It was found that plants treated with 40 ppm of SeNPS in group 3 exhibited the highest total phenolic and flavonoid content. Total phenolic content at T4 was highest for TS-5 (134%), TH-6 (132%), and Till-18 (112%). LCMS analysis revealed a total of 276 metabolites, with phenolics, flavonoids, and free fatty acids being most abundant. KEGG analysis indicated enrichment in free fatty acid and phenylalanine tryptophan pathways. ADMET analysis and virtual screening resulted in total of five metabolic compounds as a potential ligand against Hemoglobin beta subunit. Lowest binding energy was achieved by Delta-Tocopherol (-6.98) followed by Lactoflavin (-6.20) and Sesamin (-5.00). Lipinski rule of five revealed that all the compounds completely safe to be used as drug against CVD and specifically for HBB. It was concluded that bioactive compounds from sesame could be an alternative source of drug for CVD related problems and especially for HBB.
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The fruits of the tomato crop (Solanum lycopersicum L.) are increasingly consumed by humans worldwide. Due to their rich nutritional quality, pharmaceutical properties, and flavor, tomato crops have gained a salient role as standout crops among other plants. Traditional breeding and applied functional research have made progress in varying tomato germplasms to subdue biotic and abiotic stresses. Proteomic investigations within a span of few decades have assisted in consolidating the functional genomics and transcriptomic research. However, due to the volatility and dynamicity of proteins in the regulation of various biosynthetic pathways, there is a need for continuing research in the field of proteomics to establish a network that could enable a more comprehensive understanding of tomato growth and development. With this view, we provide a comprehensive review of proteomic studies conducted on the tomato plant in past years, which will be useful for future breeders and researchers working to improve the tomato crop.
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Proteômica , Solanum lycopersicum , Humanos , Solanum lycopersicum/genética , Frutas/metabolismo , Melhoramento Vegetal , Transcriptoma , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
Vegetable oil consumption is expected to reach almost 200 billion kilograms by 2030 in the world and almost 2.97 million tons in Pakistan. A large quantity of edible oil is imported annually from other countries to fill the gap between local production and consumption. Compared to other edible oil crops such as soybean, rapeseed, peanut and olive, sesame has innately higher (55%) oil content, which makes it an excellent candidate to be considered to meet local edible oil production. Oil seed crops, especially sesame, are affected by various pathogens, which results in decreased oil production with low quality oil. Selenium nanoparticles (SeNPs) work synergistically, as it has antifungal activity along with improving plant growth. Different concentrations of SeNPs were used, on three different varieties of sesame (TS-5, TH-6, and Till-18). Plant growth and development were accelerated by SeNPs, which ultimately led to an increase in crop yield. Morphological parameters revealed that SeNPs resulted in a growth increase of 55.7% in root length, 48% increase in leaf number/plant, and 38% in stem diameter. Out of three sesame varieties, TS-5 seedlings treated with 40 mg/L SeNPs showed 96.7% germination and 53% SVI at 40 mg/L. Sesame varieties dramatically increased antioxidant capability using SeNPs, resulting in 147% increase in SOD and 140% increase in POD enzyme units in TH-6 and 76% elevation in CAT enzymes in TS-5 (mean ± S.E). GCMS analysis revealed that bioactive compound I, sesamin, sesamol, and tocopherol contents were increased along with enhanced production of different unsaturated fatty acids. Kegg pathway analysis and MSEA revealed that these compounds were mainly involved in biosynthesis of unsaturated fatty acids, suggesting that SeNPs have elicited the biosynthesis of unsaturated fatty acids such as oleic acid, linoleic acid, and α-linoleic acid. This study concluded that SeNPs (40 mg/L) have an excellent capability to be used for crop improvement along with better oil quality.
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The members of ZRT, IRT-like protein (ZIP) family are involved in the uptake and transportation of several metal ions. Here, we report a comprehensive identification of ZIP transporter genes from Capsicum annuum, C. chinense, and C. baccatum, and their expression analysis under Zn and Fe stress. Changes in root morphology and differential accumulation of several metabolites from sugars, amino acids, carboxylic acids, and fatty acids in root and leaf tissues of plants in the absence of Zn and Fe were observed. Further, metabolites such as L-aspartic acid, 2-ketoglutaric acids, ß-L-fucopyranose, quininic acid, chlorogenic acid, and aucubin were significantly upregulated in root and leaf tissues under Zn/Fe deprived conditions. qRT-PCR analysis of 17 CaZIPs in different tissues revealed tissue-specific expression of CaZIP1-2, CaZIP4-8, CaZIP13, and CaZIP16-17 under normal conditions. However, the absence of Zn and Fe significantly induced the expression of CaZIP4-5, CaZIP7-9, and CaZIP14 genes in root and leaf tissues. Additionally, in the absence of Fe, upregulation of CaZIP4-5 and CaZIP8 and increased uptake of mineral elements Cu, Zn, Mg, P, and S were observed in roots, suggesting their potential role in metal-ion uptake in Capsicum. The identified genes provide the basis for future studies of mineral uptake and their biofortification to increase the nutritional values in Capsicum.
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Capsicum , Capsicum/genética , Capsicum/metabolismo , Zinco/metabolismo , Ferro/metabolismo , Proteínas de Plantas/metabolismo , Plantas/metabolismo , Proteínas de Membrana Transportadoras/genética , Verduras , Regulação da Expressão Gênica de PlantasRESUMO
Background: Hermansky-Pudlak syndrome (HSP) was first reported in 1959 as oculocutaneous albinism with bleeding abnormalities, and now consists of 11 distinct heterogenic genetic disorders that are caused by mutations in four protein complexes: AP-3, BLOC1, BLOC2, and BLOC3. Most of the patients show albinism and a bleeding diathesis; additional features may present depending on the nature of a defective protein complex. The subtypes 3 and 4 have been known for mutations in HSP3 and HSP4 genes, respectively. Methods: In this study, two Pakhtun consanguineous families, ALB-09 and ALB-10, were enrolled for clinical and molecular diagnoses. Whole-exome sequencing (WES) of the index patient in each family followed by Sanger sequencing of all available samples was performed using 3Billion. Inc South Korea rare disease diagnostics services. Results: The affected individuals of families ALB-09 and ALB-10 showed typical phenotypes of HPS such as oculocutaneous albinism, poor vision, nystagmus, nystagmus-induced involuntary head nodding, bleeding diathesis, and enterocolitis; however, immune system weakness was not recorded. WES analyses of one index patient revealed a novel nonsense variant (NM_032383.4: HSP3; c.2766T > G) in family ALB-09 and a five bp deletion (NM_001349900.2: HSP4; c.1180_1184delGTTCC) variant in family ALB-10. Sanger sequencing confirmed homozygous segregation of the disease alleles in all affected individuals of the respective family. Conclusions: The substitution c.2766T > G creates a premature protein termination at codon 922 in HPS3, replacing tyrosine amino acid with a stop codon (p.Tyr922Ter), while the deletion mutation c.1180_1184delGTTCC leads to a reading frameshift and a premature termination codon adding 23 abnormal amino acids to HSP4 protein (p:Val394Pro395fsTer23). To the best of our knowledge, the two novel variants identified in HPS3 and HPS4 genes causing Hermansky-Pudlak syndrome are the first report from the Pakhtun Pakistani population. Our work expands the pathogenic spectrum of HPS3 and HPS4 genes, provides successful molecular diagnostics, and helps the families in genetic counselling and reducing the disease burden in their future generations.
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Síndrome de Hermanski-Pudlak , Humanos , Suscetibilidade a Doenças , Mutação da Fase de Leitura , Síndrome de Hermanski-Pudlak/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Mutação , Proteínas/genéticaRESUMO
Charcot-Marie-Tooth disease (CMT) and autosomal recessive spastic ataxia of Charlevoix-Saguenay type (ARSACS) are large heterogeneous groups of sensory, neurological genetic disorders characterized by sensory neuropathies, muscular atrophies, abnormal sensory conduction velocities, and ataxia. CMT2EE (OMIM: 618400) is caused by mutations in MPV17 (OMIM: 137960), CMT4F (OMIM: 614895) is caused by PRX (OMIM: 605725), CMTX1 (OMIM: 302800) is caused by mutations in GJB1 (OMIM: 304040), and ARSACS (OMIM: 270550) is caused by mutations in SACS (OMIM: 604490). In this study, we enrolled four families: DG-01, BD-06, MR-01, and ICP-RD11, with 16 affected individuals, for clinical and molecular diagnoses. One patient from each family was analyzed for whole exome sequencing and Sanger sequencing was done for the rest of the family members. Affected individuals of families BD-06 and MR-01 show complete CMT phenotypes and family ICP-RD11 shows ARSACS type. Family DG-01 shows complete phenotypes for both CMT and ARSACS types. The affected individuals have walking difficulties, ataxia, distal limb weakness, axonal sensorimotor neuropathies, delayed motor development, pes cavus, and speech articulations with minor variations. The WES analysis in an indexed patient of family DG-01 identified two novel variants: c.83G>T (p.Gly28Val) in MPV17 and c.4934G>C (p.Arg1645Pro) in SACS. In family ICP-RD11, a recurrent mutation that causes ARSACS, c.262C>T (p.Arg88Ter) in SACS, was identified. Another novel variant, c.231C>A (p.Arg77Ter) in PRX, which causes CMT4F, was identified in family BD-06. In family MR-01, a hemizygous missense variant c.61G>C (p.Gly21Arg) in GJB1 was identified in the indexed patient. To the best of our knowledge, there are very few reports on MPV17, SACS, PRX, and GJB1 causing CMT and ARSACS phenotypes in the Pakistani population. Our study cohort suggests that whole exome sequencing can be a useful tool in diagnosing complex multigenic and phenotypically overlapping genetic disorders such as Charcot-Marie-Tooth disease (CMT) and spastic ataxia of Charlevoix-Saguenay type.