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1.
Infect Genet Evol ; 93: 104993, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34242774

RESUMO

Avian influenza virus (AIV) H7N9 that emerged in 2013 in eastern China is a novel zoonotic agent mainly circulating in poultry without clinical signs but causing severe disease with high fatality in humans in more than 5 waves. Since the emergence of highly pathogenic (HP) H7N9 variants in 2016, it has induced heavy losses in the poultry industry leading to the implementation of an intensive nationwide vaccination program at the end of wave 5 (September 2017). To characterize the ongoing evolution of H7N9 AIV, we conducted analyses of H7N9 glycoprotein genes obtained from 2013 to 2019. Bayesian analyses revealed a decreasing population size of HP H7N9 variants post wave 5. Phylogenetic topologies revealed that two novel small subclades were formed and carried several fixed amino acid mutations that were along HA and NA phylogenetic trees since wave 5. Some of the mutations were located at antigenic sites or receptor binding sites. The antigenic analysis may reveal a significant antigenic drift evaluated by hemagglutinin inhibition (HI) assay and the antigenicity of H7N9 AIV might evolute in large leaps in wave 7. Molecular simulations found that the mutations (V135T, S145P, and L226Q) around the HA receptor pocket increased the affinity to α2,3-linked sialic acid (SIA) while decreased to α2,6-linked SIA. Altered affinity may suggest that HP H7N9 variations aggravate the pathogenicity to poultry but lessen the threat to public health. Selection analyses showed that the HP H7N9 AIV experienced an increasing selection pressure since wave 5, and the national implementation of vaccination might intensify the role of natural selection during the evolution waves 6 and 7. In summary, our data provide important insights about the genetic and antigenic diversity of circulating HP H7N9 viruses from 2017 to 2019. Enhanced surveillance is urgently warranted to understand the current situation of HP H7N9 AIV.

2.
Mol Cell Biochem ; 476(7): 2837-2845, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33730298

RESUMO

Lipid metabolism, which encompasses synthesis and degradation of lipids, is critical for a wide range of cellular functions, including structural and morphological properties of organelles, energy storage, signalling, and the stability and function of membrane proteins. Adipose tissue is a dynamic tissue type that performs a lot of significant physiological functions, including secretion, and is involved in maintaining homeostasis and in regulatory roles of other tissues based on paracrine or endocrine. More recently, several classes of non-coding RNAs (ncRNAs), such as long non-coding RNA (lncRNA), microRNA (miRNA) and circular RNA (circRNA), have been discovered in adipocytes, and they act as critical regulators of gene expression in adipogenesis and regulate adipogenesis through multiple pathways. In the present paper, we discussed several classes of non-coding RNAs and summarized the latest research on the regulatory role of ncRNAs in bovine adipogenesis. We gave examples for known modes of action to look forward to providing reference information future scientific research in cattle breeding.


Assuntos
Adipogenia/fisiologia , Tecido Adiposo Branco/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Bovinos
3.
Virulence ; 12(1): 654-665, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33538238

RESUMO

Atypical porcine pestivirus (APPV) is an emerging porcine virus that threatens global swine production. Pestiviruses can prevent interferon (IFN) production to avoid the host innate immune response, and the Npro viral protein can play a critical role. Knowledge of the host immune response to APPV infection is limited. Here, we showed that the IFN-ß production was suppressed by APPV-Npro and the IFN regulatory factor 3 (IRF3) promoter activity stimulated by adaptor molecules of the IFN-ß signaling pathway was also inhibited in the APPV-Npro-expressed cells. The APPV-Npro was able to interact with IRF3 and interfere the phosphorylation of IRF3, indicated that the IFN-ß antagonism of APPV-Npro mainly depended on blocking IRF3 activity. To identify the functional region of APPV-Npro, a panel of truncated APPV-Npro was constructed, and its influence on the IRF3 activation was investigated. The results showed that the N-terminal 31-51 amino acids of APPV-Npro were mainly associated with inhibition of the IFN-ß response. Taken together, this is the first study focusing on elucidating the function of APPV protein by revealing a novel mechanism of Npro in disruption of host IFN-ß production, which will enlighten future study in addressing APPV pathogenesis and immune evasion.


Assuntos
Interferon beta/biossíntese , Pestivirus/genética , Pestivirus/imunologia , Proteínas Virais/genética , Proteínas Virais/imunologia , Animais , Linhagem Celular , Expressão Gênica , Genoma Viral , Células HEK293 , Humanos , Evasão da Resposta Imune , Fator Regulador 3 de Interferon/genética , Fator Regulador 3 de Interferon/metabolismo , Interferon beta/genética , Fosforilação , Filogenia , Transdução de Sinais , Suínos , Doenças dos Suínos/virologia
4.
Int J Mol Sci ; 21(21)2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33114322

RESUMO

Transmissible gastroenteritis virus (TGEV) is a coronavirus associated with diarrhea and high mortality in piglets. To gain insight into the evolution and adaptation of TGEV, a comprehensive analysis of phylogeny and codon usage bias was performed. The phylogenetic analyses of maximum likelihood and Bayesian inference displayed two distinct genotypes: genotypes I and II, and genotype I was classified into subtypes Ia and Ib. The compositional properties revealed that the coding sequence contained a higher number of A/U nucleotides than G/C nucleotides, and that the synonymous codon third position was A/U-enriched. The principal component analysis based on the values of relative synonymous codon usage (RSCU) showed the genotype-specific codon usage patterns. The effective number of codons (ENC) indicated moderate codon usage bias in the TGEV genome. Dinucleotide analysis showed that CpA and UpG were over-represented and CpG was under-represented in the coding sequence of the TGEV genome. The analyses of Parity Rule 2 plot, ENC-plot, and neutrality plot displayed that natural selection was the dominant evolutionary driving force in shaping codon usage preference in genotypes Ia and II. In addition, natural selection played a major role, while mutation pressure had a minor role in driving the codon usage bias in genotype Ib. The codon adaptation index (CAI), relative codon deoptimization index (RCDI), and similarity index (SiD) analyses suggested that genotype I might be more adaptive to pigs than genotype II. Current findings contribute to understanding the evolution and adaptation of TGEV.


Assuntos
Uso do Códon , Evolução Molecular , Vírus da Gastroenterite Transmissível/genética , Ilhas de CpG , Genoma Viral , Seleção Genética
5.
Viruses ; 12(9)2020 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-32899965

RESUMO

Porcine astrovirus (PAstV), associated with mild diarrhea and neurological disease, is transmitted in pig farms worldwide. The purpose of this study is to elucidate the main factors affecting codon usage to PAstVs. Phylogenetic analysis showed that the subtype PAstV-5 sat at the bottom of phylogenetic tree, followed by PAstV-3, PAstV-1, PAstV-2, and PAstV-4, indicating that the five existing subtypes (PAstV1-PAstV5) may be formed by multiple differentiations of PAstV ancestors. A codon usage bias was found in the PAstVs-2,3,4,5 from the analyses of effective number of codons (ENC) and relative synonymous codon usage (RSCU). Nucleotides A/U are more frequently used than nucleotides C/G in the genome CDSs of the PAstVs-3,4,5. Codon usage patterns of PAstV-5 are dominated by mutation pressure and natural selection, while natural selection is the main evolutionary force that affects the codon usage pattern of PAstVs-2,3,4. The analyses of codon adaptation index (CAI), relative codon deoptimization index (RCDI), and similarity index (SiD) showed the codon usage similarities between the PAstV and animals might contribute to the broad host range and the cross-species transmission of astrovirus. Our results provide insight into understanding the PAstV evolution and codon usage patterns.


Assuntos
Infecções por Astroviridae/veterinária , Astroviridae/genética , Uso do Códon , Códon/genética , Doenças dos Suínos/virologia , Adaptação Fisiológica , Animais , Astroviridae/classificação , Astroviridae/isolamento & purificação , Astroviridae/fisiologia , Infecções por Astroviridae/virologia , Genoma Viral , Filogenia , Suínos
6.
Front Genet ; 11: 777, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32903789

RESUMO

Elucidating expression patterns of heart-specific genes is crucial for understanding developmental, physiological, and pathological processes of the heart. The aim of the present study is to identify functionally and pathologically important heart-specific genes by performing the Ingenuity Pathway Analysis (IPA). Through a median-based analysis of tissue-specific gene expression based on the Genotype-Tissue Expression (GTEx) data, we identified 56 genes with heart-specific or elevated expressions in the heart (heart-specific/enhanced), among which three common heart-specific/enhanced genes and four atrial appendage-specific/enhanced genes were unreported regarding the heart. Differential expression analysis further revealed 225 differentially expressed genes (DEGs) between atrial appendage and left ventricle. Our integrative analyses of those heart-specific/enhanced genes and DEGs with IPA revealed enriched heart-related traits and diseases, consolidating evidence of relationships between these genes and heart function. Our reports on comprehensive identification of heart-specific/enhanced genes and DEGs and their relation to pathways associated with heart-related traits and diseases provided molecular insights into essential regulators of cardiac physiology and pathophysiology and potential new therapeutic targets for heart diseases.

7.
Virulence ; 11(1): 916-926, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32615860

RESUMO

Atypical porcine pestivirus (APPV) has been identified as the main causative agent for congenital tremor (CT) type A-II in piglets, which is threatening the health of the global swine herd. However, the evolution of APPV remains largely unknown. In this study, phylogenetic analysis showed that APPV could be divided into three phylogroups (I, II, and III). Phylogroups I and II included viral strains from China, while phylogroup III contained strains from Europe, North America, and Asia. Phylogroups I and II are tentatively thought to be of Chinese origin. Next, compositional property analysis revealed that a high frequency of nucleotide A and A-end codons was used in the APPV genome. Intriguingly, the analysis of preferred codons revealed that the AGA[Arg] and AGG[Arg] were overrepresented. Dinucleotide CC was found to be overrepresented, and dinucleotide CG was underrepresented. Furthermore, it was found that the weak codon usage bias of APPV was mainly dominated by selection pressures versus mutational forces. The codon adaptation index (CAI), relative codon deoptimization index (RCDI), and similarity index (SiD) analyses showed that the codon usage patterns of phylogroup II and III were more similar to the one of a pig than phylogroup I, suggesting that phylogroup II and III may be more adaptive to pigs. Overall, this study provides insights into APPV evolution through phylogeny and codon usage pattern analysis.


Assuntos
Uso do Códon , Infecções por Pestivirus/veterinária , Pestivirus/classificação , Pestivirus/genética , Filogenia , Animais , Ásia , China , Europa (Continente) , Evolução Molecular , Genoma Viral , América do Norte , Pestivirus/patogenicidade , Suínos , Doenças dos Suínos/virologia
8.
Genes (Basel) ; 11(1)2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31947640

RESUMO

Genomic imprinting in domestic animals contributes to the variance of performance traits. However, research remains to be done on large-scale detection of epigenetic landscape of porcine imprinted loci including the GNAS complex locus. The purpose of this study was to generate porcine parthenogenetic fetuses and comprehensively identify imprinting patterns of the GNAS locus in transcript levels. To this end, both normally fertilized and bimaternal (uniparental) parthenogenetic porcine fetuses were generated, and whole genome bisulfite sequencing (WGBS) and RNA sequencing (RNA-seq) were performed to construct methylome and transcriptome, respectively. Differentially methylated regions (DMRs) between the fetuses were identified through methylome analysis, and parental-origin-specific expression patterns of transcripts were examined with transcriptome. As a result, three major DMRs were identified: paternally methylated Nesp DMR, maternally methylated Nespas-Gnasxl DMR, and maternally methylated Exon1B-Exon1A DMR. Parental-origin-specific expressions of those five DMR-affected transcripts were found, including a novel imprinted transcript, Exon1B, in pigs. In conclusion, using parthenotes, parental-origin-specific imprinting patterns in the porcine GNAS locus was comprehensively identified, and our approach paves the way for the discovery of novel imprinted genes and loci in a genomic context across species.


Assuntos
Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Impressão Genômica/genética , Suínos/genética , Animais , Sequência de Bases/genética , Metilação de DNA/genética , Epigênese Genética/genética , Epigenoma/genética , Éxons/genética , Feto , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Genoma/genética , Partenogênese , Regiões Promotoras Genéticas/genética , Análise de Sequência de RNA/métodos , Transcriptoma/genética
9.
Sci Rep ; 9(1): 3087, 2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-30816281

RESUMO

Identification of adipose-specific genes has contributed to an understanding of mechanisms underlying adipocyte development and obesity. Herein, our analyses of the recent Genotype-Tissue Expression (GTEx) database revealed 38 adipose-specific/enhanced protein coding genes, among which 3 genes were novel adipose-specific, and 414 highly differentially expressed genes (DEGs) between subcutaneous and omental adipose depots. By integrative analyses of genome-wide association studies (GWASs), 14 adipose-specific/enhanced genes and 60 DEGs were found to be associated with obesity-related traits and diseases, consolidating evidence for contribution of these genes to the regional fat distribution and obesity phenotypes. In addition, expression of HOXC cluster was up-regulated in subcutaneous adipose tissue, and the majority of the HOXB cluster was expressed highly in omental adipose tissue, indicating differential expression patterns of HOX clusters in adipose depots. Our findings on the distinct gene expression profiles in adipose tissue and their relation to obesity provide an important foundation for future functional biological studies and therapeutic targets in obesity and associated diseases.


Assuntos
Gordura Abdominal/metabolismo , Adipócitos/metabolismo , Estudo de Associação Genômica Ampla , Obesidade/genética , Omento/metabolismo , Gordura Subcutânea/metabolismo , Gordura Abdominal/citologia , Adipócitos/citologia , Conjuntos de Dados como Assunto , Genes Homeobox , Loci Gênicos , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Omento/citologia , Gordura Subcutânea/citologia , Transcriptoma
10.
Nat Genet ; 50(12): 1696-1704, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30397334

RESUMO

The genetic variation in Northern Asian populations is currently undersampled. To address this, we generated a new genetic variation reference panel by whole-genome sequencing of 175 ethnic Mongolians, representing six tribes. The cataloged variation in the panel shows strong population stratification among these tribes, which correlates with the diverse demographic histories in the region. Incorporating our results with the 1000 Genomes Project panel identifies derived alleles shared between Finns and Mongolians/Siberians, suggesting that substantial gene flow between northern Eurasian populations has occurred in the past. Furthermore, we highlight that North, East, and Southeast Asian populations are more aligned with each other than these groups are with South Asian and Oceanian populations.


Assuntos
Grupo com Ancestrais do Continente Asiático/etnologia , Grupo com Ancestrais do Continente Asiático/genética , Genética Populacional , América/epidemiologia , Ásia Setentrional/epidemiologia , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Europa (Continente)/epidemiologia , Extremo Oriente/epidemiologia , Feminino , Fluxo Gênico , Genoma Humano , Humanos , Masculino , Mongólia/etnologia , Filogenia , Sequenciamento Completo do Genoma
11.
Exp Ther Med ; 15(5): 4185-4190, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29731817

RESUMO

When stimulated, mesenchymal stem cells (MSCs) may differentiate into chondroblasts, adipocytes or osteoblasts. Leptin is an adipocyte-derived hormone, which regulates food intake and glucose homeostasis. The aim of the present study was to identify the potential role of mitogen-activated protein kinase in the leptin-induced growth of rabbit bone MSCs (rBMSCs). Various concentrations of leptin were used to culture rBMSCs and the viability of cells was observed as well as alterations in the phosphorylation state of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase and p38. It was revealed that the growth of leptin-treated rBMSCs was primarily inhibited by phosphorylated ERK1/2, which was mediated by the leptin receptor. In conclusion, the results of the present study demonstrated that leptin inhibits the growth of rBMSCs principally via the ERK1/2 signaling pathway.

13.
Genome Biol Evol ; 6(12): 3122-36, 2014 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-25377941

RESUMO

Mongolians have played a significant role in modern human evolution, especially after the rise of Genghis Khan (1162[?]-1227). Although the social cultural impacts of Genghis Khan and the Mongolian population have been well documented, explorations of their genome structure and genetic imprints on other human populations have been lacking. We here present the genome of a Mongolian male individual. The genome was de novo assembled using a total of 130.8-fold genomic data produced from massively parallel whole-genome sequencing. We identified high-confidence variation sets, including 3.7 million single nucleotide polymorphisms (SNPs) and 756,234 short insertions and deletions. Functional SNP analysis predicted that the individual has a pathogenic risk for carnitine deficiency. We located the patrilineal inheritance of the Mongolian genome to the lineage D3a through Y haplogroup analysis and inferred that the individual has a common patrilineal ancestor with Tibeto-Burman populations and is likely to be the progeny of the earliest settlers in East Asia. We finally investigated the genetic imprints of Mongolians on other human populations using different approaches. We found varying degrees of gene flows between Mongolians and populations living in Europe, South/Central Asia, and the Indian subcontinent. The analyses demonstrate that the genetic impacts of Mongolians likely resulted from the expansion of the Mongolian Empire in the 13th century. The genome will be of great help in further explorations of modern human evolution and genetic causes of diseases/traits specific to Mongolians.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Evolução Molecular , Fluxo Gênico , Genoma Humano , População/genética , Carnitina/deficiência , Carnitina/genética , Deleção de Genes , Humanos , Masculino , Mongólia , Mutagênese Insercional , Polimorfismo de Nucleotídeo Único
14.
Nat Commun ; 5: 5188, 2014 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-25333821

RESUMO

Bactrian camel (Camelus bactrianus), dromedary (Camelus dromedarius) and alpaca (Vicugna pacos) are economically important livestock. Although the Bactrian camel and dromedary are large, typically arid-desert-adapted mammals, alpacas are adapted to plateaus. Here we present high-quality genome sequences of these three species. Our analysis reveals the demographic history of these species since the Tortonian Stage of the Miocene and uncovers a striking correlation between large fluctuations in population size and geological time boundaries. Comparative genomic analysis reveals complex features related to desert adaptations, including fat and water metabolism, stress responses to heat, aridity, intense ultraviolet radiation and choking dust. Transcriptomic analysis of Bactrian camels further reveals unique osmoregulation, osmoprotection and compensatory mechanisms for water reservation underpinned by high blood glucose levels. We hypothesize that these physiological mechanisms represent kidney evolutionary adaptations to the desert environment. This study advances our understanding of camelid evolution and the adaptation of camels to arid-desert environments.


Assuntos
Adaptação Fisiológica/genética , Evolução Biológica , Camelus/genética , Genoma , Transcriptoma , Tecido Adiposo/metabolismo , Animais , Glicemia/química , Clima Desértico , Meio Ambiente , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Dados de Sequência Molecular , Osmorregulação , Filogenia , Sódio/metabolismo , Especificidade da Espécie , Transcrição Genética , Raios Ultravioleta , Água/química
15.
BMC Med Genet ; 15: 34, 2014 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-25008054

RESUMO

BACKGROUND: The genetic basis of autosomal dominant nonsyndromic hearing loss is complex. Genetic factors are responsible for approximately 50% of cases with congenital hearing loss. However, no previous studies have documented the clinical phenotype and genetic basis of autosomal dominant nonsyndromic hearing loss in Mongolians. METHODS: In this study, we performed exon capture sequencing of a Mongolian family with hereditary hearing loss and identified a novel mutation in TECTA gene, which encodes α -tectorin, a major component of the inner ear extracellular matrix that contacts the specialized sensory hair cells. RESULTS: The novel G → T missense mutation at nucleotide 6016 results in a substitution of amino acid aspartate at 2006 with tyrosine (Asp2006Tyr) in a highly conserved zona pellucida (ZP) domain of α-tectorin. The mutation is not found in control subjects from the same family with normal hearing and a genotype-phenotype correlation is observed. CONCLUSION: A novel missense mutation c.6016 G > T (p.Asp2006Tyr) of TECTA gene is a characteristic TECTA-related mutation which causes autosomal dominant nonsyndromic hearing loss. Our result indicated that mutation in TECTA gene is responsible for the hearing loss in this Mongolian family.


Assuntos
Proteínas da Matriz Extracelular/genética , Genes Dominantes , Perda Auditiva/genética , Mutação , Adolescente , Adulto , Idoso , Sequência de Aminoácidos , Audiometria , Criança , Pré-Escolar , China , Análise Mutacional de DNA , Proteínas da Matriz Extracelular/química , Feminino , Proteínas Ligadas por GPI/química , Proteínas Ligadas por GPI/genética , Estudos de Associação Genética , Perda Auditiva/diagnóstico , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação de Sentido Incorreto , Linhagem , Alinhamento de Sequência , Adulto Jovem
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