scholarly journals Whole genome sequencing of live attenuated bovine adenovirus type 7 vaccine strain TS-GT reveals biomarkers for virulence attenuation

Author(s):  
Asuka Kumagai ◽  
Sayo Kajikawa ◽  
Ayako Miyazaki ◽  
Shinichi Hatama

Abstract Bovine adenovirus type 7 (BAdV-7) is one of the most important respiratory and enteric pathogens in the cattle industry. Although live attenuated vaccines are used to control the virus in Japan, limited information is available on the genomic regions that determine viral pathogenicity. Here we analyzed the attenuated strain TS-GT after isolation of the virus from the hexavalent bovine respiratory disease vaccine Cattlewin-6 lot #40-1. The complete genome sequence of TS-GT was determined using next-generation sequencing. The genome is 30,052 bp long and contains 45-bp inverted terminal repeats (ITR) and 30 predicted genes. A genome sequence comparison showed that 99.9% of the TS-GT genome is identical to the prototypic and pathogenic BAdV-7 strain Fukuroi; however, the TS-GT genome contains a novel mutation and four indels. A mutation in TS-GT of the minor capsid protein pVI causes an amino acid change, and possibly induces an alteration of its membrane-lytic function; this may underlie the temperature-specific growth characteristic of this strain. A 19-bp insertion in the 3’ ITR may affect its promoter activity and change the expression of downstream coding genes. In this way, the insertion may play important roles in the attenuation of the virus. Although further mutational and functional analyses are required, our results provide insights into the molecular basis of BAdV-7 attenuation and open new avenues for future analyses.

2021 ◽  
Vol 10 (10) ◽  
Author(s):  
Asuka Kumagai ◽  
Sayo Kajikawa ◽  
Ayako Miyazaki ◽  
Shinichi Hatama

ABSTRACT We determined the complete genome sequence of the bovine adenovirus type 7 prototype strain Fukuroi using next-generation sequencing technology. We found that the viral genome is 30,034 bp long and has the shortest inverted terminal repeats among known adenoviruses.


2011 ◽  
Vol 8 (1) ◽  
pp. 557 ◽  
Author(s):  
Yuan-Mao Zhu ◽  
Zuo Yu ◽  
Hong Cai ◽  
Yu-Ran Gao ◽  
Xiu-Mei Dong ◽  
...  

2020 ◽  
Vol 48 (22) ◽  
pp. 12604-12617
Author(s):  
Pengpeng Long ◽  
Lu Zhang ◽  
Bin Huang ◽  
Quan Chen ◽  
Haiyan Liu

Abstract We report an approach to predict DNA specificity of the tetracycline repressor (TetR) family transcription regulators (TFRs). First, a genome sequence-based method was streamlined with quantitative P-values defined to filter out reliable predictions. Then, a framework was introduced to incorporate structural data and to train a statistical energy function to score the pairing between TFR and TFR binding site (TFBS) based on sequences. The predictions benchmarked against experiments, TFBSs for 29 out of 30 TFRs were correctly predicted by either the genome sequence-based or the statistical energy-based method. Using P-values or Z-scores as indicators, we estimate that 59.6% of TFRs are covered with relatively reliable predictions by at least one of the two methods, while only 28.7% are covered by the genome sequence-based method alone. Our approach predicts a large number of new TFBs which cannot be correctly retrieved from public databases such as FootprintDB. High-throughput experimental assays suggest that the statistical energy can model the TFBSs of a significant number of TFRs reliably. Thus the energy function may be applied to explore for new TFBSs in respective genomes. It is possible to extend our approach to other transcriptional factor families with sufficient structural information.


Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 246
Author(s):  
Xiaomeng Chen ◽  
Rui Li ◽  
Yonglin Wang ◽  
Aining Li

An emerging poplar canker caused by the gram-negative bacterium, Lonsdalea populi, has led to high mortality of hybrid poplars Populus × euramericana in China and Europe. The molecular bases of pathogenicity and bark adaptation of L. populi have become a focus of recent research. This study revealed the whole genome sequence and identified putative virulence factors of L. populi. A high-quality L. populi genome sequence was assembled de novo, with a genome size of 3,859,707 bp, containing approximately 3434 genes and 107 RNAs (75 tRNA, 22 rRNA, and 10 ncRNA). The L. populi genome contained 380 virulence-associated genes, mainly encoding for adhesion, extracellular enzymes, secretory systems, and two-component transduction systems. The genome had 110 carbohydrate-active enzyme (CAZy)-coding genes and putative secreted proteins. The antibiotic-resistance database annotation listed that L. populi was resistant to penicillin, fluoroquinolone, and kasugamycin. Analysis of comparative genomics found that L. populi exhibited the highest homology with the L. britannica genome and L. populi encompassed 1905 specific genes, 1769 dispensable genes, and 1381 conserved genes, suggesting high evolutionary diversity and genomic plasticity. Moreover, the pan genome analysis revealed that the N-5-1 genome is an open genome. These findings provide important resources for understanding the molecular basis of the pathogenicity and biology of L. populi and the poplar-bacterium interaction.


Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1984
Author(s):  
Majid Nikpay ◽  
Sepehr Ravati ◽  
Robert Dent ◽  
Ruth McPherson

Here, we performed a genome-wide search for methylation sites that contribute to the risk of obesity. We integrated methylation quantitative trait locus (mQTL) data with BMI GWAS information through a SNP-based multiomics approach to identify genomic regions where mQTLs for a methylation site co-localize with obesity risk SNPs. We then tested whether the identified site contributed to BMI through Mendelian randomization. We identified multiple methylation sites causally contributing to the risk of obesity. We validated these findings through a replication stage. By integrating expression quantitative trait locus (eQTL) data, we noted that lower methylation at cg21178254 site upstream of CCNL1 contributes to obesity by increasing the expression of this gene. Higher methylation at cg02814054 increases the risk of obesity by lowering the expression of MAST3, whereas lower methylation at cg06028605 contributes to obesity by decreasing the expression of SLC5A11. Finally, we noted that rare variants within 2p23.3 impact obesity by making the cg01884057 site more susceptible to methylation, which consequently lowers the expression of POMC, ADCY3 and DNAJC27. In this study, we identify methylation sites associated with the risk of obesity and reveal the mechanism whereby a number of these sites exert their effects. This study provides a framework to perform an omics-wide association study for a phenotype and to understand the mechanism whereby a rare variant causes a disease.


BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Benjamin Soibam ◽  
Ayzhamal Zhamangaraeva

Abstract Background Chromosomes are organized into units called topologically associated domains (TADs). TADs dictate regulatory landscapes and other DNA-dependent processes. Even though various factors that contribute to the specification of TADs have been proposed, the mechanism is not fully understood. Understanding the process for specification and maintenance of these units is essential in dissecting cellular processes and disease mechanisms. Results In this study, we report a genome-wide study that considers the idea of long noncoding RNAs (lncRNAs) mediating chromatin organization using lncRNA:DNA triplex-forming sites (TFSs). By analyzing the TFSs of expressed lncRNAs in multiple cell lines, we find that they are enriched in TADs, their boundaries, and loop anchors. However, they are evenly distributed across different regions of a TAD showing no preference for any specific portions within TADs. No relationship is observed between the locations of these TFSs and CTCF binding sites. However, TFSs are located not just in promoter regions but also in intronic, intergenic, and 3’UTR regions. We also show these triplex-forming sites can be used as predictors in machine learning models to discriminate TADs from other genomic regions. Finally, we compile a list of important “TAD-lncRNAs” which are top predictors for TADs identification. Conclusions Our observations advocate the idea that lncRNA:DNA TFSs are positioned at specific areas of the genome organization and are important predictors for TADs. LncRNA:DNA triplex formation most likely is a general mechanism of action exhibited by some lncRNAs, not just for direct gene regulation but also to mediate 3D chromatin organization.


Genetics ◽  
2003 ◽  
Vol 164 (1) ◽  
pp. 247-258 ◽  
Author(s):  
Jinghong Li ◽  
Willis X Li

Abstract Overactivation of receptor tyrosine kinases (RTKs) has been linked to tumorigenesis. To understand how a hyperactivated RTK functions differently from wild-type RTK, we conducted a genome-wide systematic survey for genes that are required for signaling by a gain-of-function mutant Drosophila RTK Torso (Tor). We screened chromosomal deficiencies for suppression of a gain-of-function mutation tor (torGOF), which led to the identification of 26 genomic regions that, when in half dosage, suppressed the defects caused by torGOF. Testing of candidate genes in these regions revealed many genes known to be involved in Tor signaling (such as those encoding the Ras-MAPK cassette, adaptor and structural molecules of RTK signaling, and downstream target genes of Tor), confirming the specificity of this genetic screen. Importantly, this screen also identified components of the TGFβ (Dpp) and JAK/STAT pathways as being required for TorGOF signaling. Specifically, we found that reducing the dosage of thickveins (tkv), Mothers against dpp (Mad), or STAT92E (aka marelle), respectively, suppressed torGOF phenotypes. Furthermore, we demonstrate that in torGOF embryos, dpp is ectopically expressed and thus may contribute to the patterning defects. These results demonstrate an essential requirement of noncanonical signaling pathways for a persistently activated RTK to cause pathological defects in an organism.


2021 ◽  
Author(s):  
Nicolas Pompidor ◽  
Carine Charron ◽  
Catherine Hervouet ◽  
Stéphanie Bocs ◽  
Gaëtan Droc ◽  
...  

Abstract Background and Aims Modern sugarcane cultivars (Saccharum spp.) are high polyploids, aneuploids (2n = ~12x = ~120) derived from interspecific hybridizations between the domesticated sweet species Saccharum officinarum and the wild species S. spontaneum. Methods To analyse the architecture and origin of such a complex genome, we analysed the sequences of all 12 hom(oe)ologous haplotypes (BAC clones) from two distinct genomic regions of a typical modern cultivar, as well as the corresponding sequence in Miscanthus sinense and Sorghum bicolor, and monitored their distribution among representatives of the Saccharum genus. Key Results The diversity observed among haplotypes suggested the existence of three founding genomes (A, B, C) in modern cultivars, which diverged between 0.8 and 1.3 Mya. Two genomes (A, B) were contributed by S. officinarum; these were also found in its wild presumed ancestor S. robustum, and one genome (C) was contributed by S. spontaneum. These results suggest that S. officinarum and S. robustum are derived from interspecific hybridization between two unknown ancestors (A and B genomes). The A genome contributed most haplotypes (nine or ten) while the B and C genomes contributed one or two haplotypes in the regions analysed of this typical modern cultivar. Interspecific hybridizations likely involved accessions or gametes with distinct ploidy levels and/or were followed by a series of backcrosses with the A genome. The three founding genomes were found in all S. barberi, S. sinense and modern cultivars analysed. None of the analysed accessions contained only the A genome or the B genome, suggesting that representatives of these founding genomes remain to be discovered. Conclusions This evolutionary model, which combines interspecificity and high polyploidy, can explain the variable chromosome pairing affinity observed in Saccharum. It represents a major revision of the understanding of Saccharum diversity.


2021 ◽  
Vol 53 (1) ◽  
Author(s):  
Martin Johnsson ◽  
Andrew Whalen ◽  
Roger Ros-Freixedes ◽  
Gregor Gorjanc ◽  
Ching-Yi Chen ◽  
...  

Abstract Background Meiotic recombination results in the exchange of genetic material between homologous chromosomes. Recombination rate varies between different parts of the genome, between individuals, and is influenced by genetics. In this paper, we assessed the genetic variation in recombination rate along the genome and between individuals in the pig using multilocus iterative peeling on 150,000 individuals across nine genotyped pedigrees. We used these data to estimate the heritability of recombination and perform a genome-wide association study of recombination in the pig. Results Our results confirmed known features of the recombination landscape of the pig genome, including differences in genetic length of chromosomes and marked sex differences. The recombination landscape was repeatable between lines, but at the same time, there were differences in average autosome-wide recombination rate between lines. The heritability of autosome-wide recombination rate was low but not zero (on average 0.07 for females and 0.05 for males). We found six genomic regions that are associated with recombination rate, among which five harbour known candidate genes involved in recombination: RNF212, SHOC1, SYCP2, MSH4 and HFM1. Conclusions Our results on the variation in recombination rate in the pig genome agree with those reported for other vertebrates, with a low but nonzero heritability, and the identification of a major quantitative trait locus for recombination rate that is homologous to that detected in several other species. This work also highlights the utility of using large-scale livestock data to understand biological processes.


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