Genomic characteristic

基因组特征
  • 文章类型: Journal Article
    为了扩大我们对中国鸽子副粘病毒1型(PPMV-1)流行病学的认识,2014-2021年对从活禽市场收集的鸽子拭子进行了基于风险的主动监测.在所调查的20个省份中,12个省份(60%)分离出PPMV-1菌株76株,PPMV-1的阳性率每年从0.50%到3.19%不等。分析了18种代表性病毒的完整基因组序列,揭示了15192个核苷酸的基因组,基因顺序为3\'-NP-P-M-F-HN-L-5\'。所有分离株在融合(F)蛋白中都含有112RRQKRF117切割位点,通常与毒力新城疫病毒(NDV)相关的特征,四个分离株的脑内致病性指数值(1.05-1.41)表明其毒力。一项挑战实验还表明,所有四种分离株都对鸽子有致病性,发病率为60-100%,死亡率为0-30%。对F和HN蛋白的功能结构域的进一步分析揭示了融合肽中的几种突变,信号肽,中和表位,七肽重复区,和跨膜结构域,半胱氨酸残基25(C25Y)的取代以及F蛋白HRb区(V287I)和HN蛋白跨膜结构域(V45A)的取代可能在PPMV-1毒力中起重要作用。在基于F基因完整序列的系统发育分析中,所有18个分离株都聚集在II类子基因型VI.2.1.2.2(VIb)中,并共享高核苷酸序列同一性,表明子基因型VI.1.1.1.2.2中的PPMV-1毒株是中国鸽子中的主要PPMV-1病毒,并且这些病毒的变异在过去8年中相对稳定。这项研究确定了在中国流行的PPMV-1株的遗传和致病性特征,并扩展了我们对该病毒在中国流行的认识。
    To expand our understanding of the epidemiology of pigeon paramyxovirus type 1 (PPMV-1) in China, risk-based active surveillance was undertaken with pigeon swabs collected from live bird markets in 2014-2021. Seventy-six PPMV-1 strains were isolated from 12 provinces (60%) of the 20 provinces surveyed, and the positive rates of PPMV-1 varied from 0.50% to 3.19% annually. The complete genomic sequences of 18 representative viruses were analyzed, revealing a genome of 15,192 nucleotides, with the gene order 3\'-NP-P-M-F-HN-L-5\'. All isolates contained the 112RRQKRF117 cleavage site in the fusion (F) protein, a characteristic generally associated with virulent Newcastle disease viruses (NDVs), and the intracerebral pathogenicity index values (1.05-1.41) of four isolates indicated their virulence. A challenge experiment also demonstrated that all four isolates are pathogenic to pigeons, with morbidity rates of 60-100% and mortality rates of 0-30%. A further analysis of the functional domains of the F and HN proteins revealed several mutations in the fusion peptide, signal peptide, neutralizing epitopes, heptad repeat region, and transmembrane domains, and the substitution of cysteine residue 25 (C25Y) and substitutions in the HRb region (V287I) of the F protein and the transmembrane domain (V45A) of the HN protein may play important roles in PPMV-1 virulence. In a phylogenetic analysis based on the complete sequences of the F gene, all eighteen isolates all clustered into sub-genotype VI.2.1.1.2.2 (VIb) in class II, and shared high nucleotide sequence identity, indicating that the PPMV-1 strains in sub-genotype VI.2.1.1.2.2 are the predominant PPMV-1 viruses in pigeons in China and that the variations in these viruses have been relatively stable over the past 8 years. This study identifies the genetic and pathogenicity characteristics of the PPMV-1 strains prevalent in China and extends our understanding of the prevalence of this virus in China.
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  • 文章类型: Journal Article
    对虾(对虾科)是经济和生态上最重要的甲壳类动物之一。然而,在过去的20年中,他们的基因组测序和组装遇到了极大的困难。在这项研究中,根据我们以前的基因组数据,我们调查了四种对虾物种的基因组特征,并确定了导致其基因组组装不良的潜在因素,包括杂合性,多倍体化,并重复。基因组测序和四种虾种的体细胞(二倍体)和凡纳滨对虾的单个精子细胞(单倍体)的比较确定了K-mer深度的共同双峰分布,表明它们的基因组中存在高杂合性或丰富的同源重复序列。然而,正如一系列方法所表明的,对虾没有经历全基因组复制。此外,简单序列重复的显着扩展是对虾基因组的另一个突出特征,这也使得基因组组装高度碎片化。由于这种情况,我们尝试使用各种基因组测序和组装策略组装对虾的基因组,并比较了质量。因此,这项研究为对虾的基因组特征提供了新的见解,同时改善了它们的基因组组装。
    Penaeid shrimp (family Penaeidae) represents one of the most economically and ecologically important groups of crustaceans. However, their genome sequencing and assembly have encountered extreme difficulties during the last 20 years. In this study, based on our previous genomic data, we investigated the genomic characteristics of four penaeid shrimp species and identified potential factors that result in their poor genome assembly, including heterozygosity, polyploidization, and repeats. Genome sequencing and comparison of somatic cells (diploid) of the four shrimp species and a single sperm cell (haploid) of Litopenaeus vannamei identified a common bimodal distribution of K-mer depths, suggesting either high heterozygosity or abundant homo-duplicated sequences present in their genomes. However, penaeids have not undergone whole-genome duplication as indicated by a series of approaches. Besides, the remarkable expansion of simple sequence repeats was another outstanding character of penaeid genomes, which also made the genome assembly highly fragmented. Due to this situation, we tried to assemble the genome of penaeid shrimp using various genome sequencing and assembly strategies and compared the quality. Therefore, this study provides new insights about the genomic characteristics of penaeid shrimps while improving their genome assemblies.
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  • 文章类型: Journal Article
    Due to its drug resistant nature, β-lactamase represents a serious challenge for public health. Extended-spectrum β-lactamase (ESBL) producing Klebsiella pneumoniae clones are increasingly reported worldwide. Little is known about the prevalence and biological characteristics of drug-resistant strains in zoos. During routine surveillance at the Zhengzhou Zoo of China, we found Klebsiella pneumoniae isolate in healthy Red Kangaroos (Macropus Rufus) with severe MDR. The Klebsiella pneumoniae were especially resistant to Cefuroxime Sodium (MIC, > 64 μg/mL), Ceftriaxone (MIC, >8 μg/mL) and Cefepime (MIC, >64 μg/mL), and belonged to ST290. Subsequently, whole genome sequencing (WGS) showed that the Chrome Chr-M297-1 harbored bla DHA-3, bla SHV-1, bla CTX-M-14, fosA5, dfrA3, sul3, etc., and pM297-1.1 [222,864 bp, IncFIB(K)], which carried nine antimicrobial genes including bla CTX-M-14, bla TEM-191, aph(3″)-Ib, aph(6)-Id and qnrS1, etc., and pM297-1.2 [225,763 bp, IncFII(K)] carried 22 antimicrobial genes including bla TEM-1, bla CTX-M-3, aph(3\')-Ia, aac(3)-IIa, aac(6\')-Ib-cr, aadA16, qnrB2, qnrS1, qacEΔ1, mphA, sul1, and dfrA27, etc. A traceability analysis then revealed that these two plasmids were highly similar to those recovered from human clinical samples in some southern cities in Sichuan Province, China (>99%), suggesting that these plasmids are spreading in China. Furthermore, two plasmids harboring conjugal transfer genes facilitated the transmission of antimicrobial genes by conjugation with E. coli J53. Our research shows that the transmission and adaptation of Klebsiella pneumoniae producing ESBLs is occurring in zoo environments, suggesting that zoos may be becoming important potential reservoirs for clinically important drug-resistant genes. It is therefore necessary to monitor the emergence and spread of drug-resistant gene strains in captive wild animals held in zoo environments.
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  • 文章类型: Journal Article
    背景:晚期软组织肉瘤(STS)患者的预后不佳,几乎没有有效的治疗选择。同源重组修复(HRR)途径的缺陷可以积累DNA修复错误和基因突变,会导致肿瘤发生.BRCAness描述了在不存在种系BRCA1/2突变的情况下具有HRR缺陷(HRD)的肿瘤。然而,STS中BRCAness的特征在很大程度上仍然未知。因此,本研究旨在利用STS中的全外显子组测序(WES)探索BRCAness的基因组和分子景观,旨在寻找STS治疗的潜在目标。方法:对中山大学附属第一医院22例STS样本进行WES,揭示可能的基因组和分子特征。然后使用来自癌症基因组图谱(TCGA)数据库的224个STS样品的数据和体外数据来验证特征。对BRCAness的潜在生物标志物进行分析。在STS细胞系中评估了STS化疗药物的靶向药物敏感性和联合治疗筛选,细胞系来源的异种移植物(CDX),和患者来源的异种移植物(PDX)。结果:与30种癌症的体细胞突变特征相比,在22个STS样本中,使用非负矩阵因子分解法鉴定出HRD特征的高余弦相似度(0.75).单核苷酸多态性表明22例STS样本中BRCA1/2突变率较低(11.76%和5.88%,分别)。然而,拷贝数变异分析证明了广泛的染色体不稳定性;此外,54.55%(12/22)的STS样本具有BRCAness性状。随后,在来自TCGA和体外的224份STS样本中也检测到相似的基因组和分子特征.聚(ADP-核糖)聚合酶(PARP)-1可能是HRD和治疗反应的有希望的反映。此外,发现PAR形成水平与PARP-1相关。随后,确定STS细胞系对PARP抑制剂(PARPi)敏感,尼拉帕利。此外,基于五种常见PARPis的筛选试验和阿霉素的联合试验,异环磷酰胺,达卡巴嗪,和替莫唑胺(TMZ),尼拉帕尼和TMZ在STS细胞系中的协同作用最强。在CDX和PDX中还显示了尼拉帕尼和TMZ组合的协同作用和安全性。结论:BRCAness可能是大多数STS病例的共同基因组和分子特征。PARP-1和PAR可能是评估患者HRD的潜在适当和可行的治疗诊断生物标志物。STS对PARPi敏感。此外,尼拉帕尼和TMZ的组合显示出协同作用。Niraparib和TMZ可能是STS患者的有希望的靶向治疗策略。
    Background: Patients with advanced soft tissue sarcomas (STS) have a dismal prognosis with few effective therapeutic options. A defect in the homologous recombination repair (HRR) pathway can accumulate DNA repair errors and gene mutations, which can lead to tumorigenesis. BRCAness describes tumors with an HRR deficiency (HRD) in the absence of a germline BRCA1/2 mutation. However, the characteristics of BRCAness in STS remain largely unknown. Thus, this study aimed to explore the genomic and molecular landscape of BRCAness using whole exome sequencing (WES) in STS, aiming to find a potential target for STS treatment. Methods: WES was performed in 22 STS samples from the First Affiliated Hospital of Sun Yat-sen University to reveal the possible genomic and molecular characteristics. The characteristics were then validated using data of 224 STS samples from The Cancer Genome Atlas (TCGA) database and in vitro data. The analysis of the potential biomarker for BRCAness was performed. Targeted drug susceptibility and combination therapy screening of chemotherapeutics for STS were evaluated in STS cell lines, cell-line-derived xenografts (CDX), and patient-derived xenografts (PDX). Results: Compared with 30 somatic mutation signatures of cancers, high cosine-similarity (0.75) was identified for HRD signatures in the 22 STS samples using nonnegative matrix factorization. Single nucleotide polymorphism indicated a low mutation rate of BRCA1/2 in the 22 STS samples (11.76% and 5.88%, respectively). However, copy number variation analyses demonstrated widespread chromosomal instability; furthermore, 54.55% of STS samples (12/22) carried BRCAness traits. Subsequently, similar genomic and molecular characteristics were also detected in the 224 STS samples from TCGA and in vitro. Poly (ADP-ribose) polymerases (PARP)-1 could be a promising reflection of HRD and therapeutic response. Furthermore, the level of PAR formation was found to be correlated with PARP-1. Subsequently, STS cell lines were determined to be sensitive to PARP inhibitor (PARPi), niraparib. Moreover, based on the screening test of the five common PARPis and combination test among doxorubicin, ifosfamide, dacarbazine, and temozolomide (TMZ), niraparib and TMZ were the most synergistic in STS cell lines. The synergistic effect and safety of niraparib and TMZ combination were also shown in CDX and PDX. Conclusions: BRCAness might be the common genomic and molecular characteristics of majority of STS cases. PARP-1 and PAR could be potential proper and feasible theranostic biomarkers for assessing HRD in patients. STSs were sensitive to PARPi. Moreover, the combination of niraparib and TMZ showed synergistic effect. Niraparib and TMZ could be a promising targeted therapeutic strategy for patients with STS.
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  • 文章类型: Journal Article
    The St genome, originating from Pseudoroegneria (Nevski) Á. Löve, plays an important role in Triticeae. In this study, the Pseudoroegneria stipifolia genome (2n = 2x = 14, StSt) was screened to identify sequences that could be used for FISH. A total of 163 effective clones were obtained from the genomic plasmid library which was constructed by DNase I digestion of P. stipifolia nuclear genomic DNA. Analysis of these clones identified 112 with characteristics of transposable elements (TEs), 13 with characteristics of tandem repetitive sequences, 8 with characteristics of mRNA sequences, and 30 unknown sequences. Fluorescent signals were detected for 11 of 41 TE sequences on P. stipifolia chromosomes after in situ hybridization and were divided into 4 types according to signal distribution patterns: over the whole St genome chromosomes, telomere to pericentromeric regions, centromere to pericentromeric regions, and terminal regions. The affinity between St and Y genomes was studied using the 11 TE probes in 3 StStYY species. Five TE probes showed no obvious difference between subgenomes, 2 probes displayed divergence only in 2 StStYY species, and 4 probes exhibited significant differences among 3 StStYY species. These results provide a preliminary understanding of the sequence composition of the St genome and enabled 11 novel TE probes to be developed and applied.
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  • 文章类型: Journal Article
    BACKGROUND: Urban rodents and house shrews are closely correlated in terms of location with humans and can transmit many pathogens to them. Hepatitis E has been confirmed to be a zoonotic disease. However, the zoonotic potential of rat HEV is still unclear. The aim of this study was to determine the prevalence and genomic characteristics of hepatitis E virus (HEV) in rodents and house shrews.
    RESULTS: We collected a total of 788 animals from four provinces in China. From the 614 collected murine rodents, 20.19% of the liver tissue samples and 45.76% of the fecal samples were positive for HEV. From the 174 house shrews (Suncus murinus), 5.17% fecal samples and 0.57% liver tissue samples were positive for HEV. All of the HEV sequences obtained in this study belonged to Orthohepevirus C1. However, we observed a lower percentage of identity in the ORF3 region upon comparing the amino acid sequences between Rattus norvegicus and Rattus losea. HEV derived from house shrews shared a high percentage of identity with rat HEV. Notably, the first near full-length of the HEV genome from Rattus losea is described in our study, and we also report the first near full-length rat HEV genomes in Rattus norvegicus from China.
    CONCLUSIONS: HEV is prevalent among the three common species of murine rodents (Rattus. norvegicus, Rattus. tanezumi, and Rattus. losea) in China. HEV sequences detected from house shrews were similar to rat HEV sequences. The high identity of HEV from murine rodents and house shrews suggested that HEV can spread among different animal species.
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