scholarly journals Whole-genome resequencing and pan-transcriptome reconstruction highlight the impact of genomic structural variation on secondary metabolism gene clusters in the grapevine Esca pathogenPhaeoacremonium minimum

2018 ◽  
Author(s):  
Mélanie Massonnet ◽  
Abraham Morales-Cruz ◽  
Andrea Minio ◽  
Rosa Figueroa-Balderas ◽  
Daniel P. Lawrence ◽  
...  
Keyword(s):  
Secondary Metabolism ◽  
Single Molecule ◽  
Structural Variation ◽  
Phenotypic Variability ◽  
Gene Clusters ◽  
Intraspecific Diversity ◽  
Cellular Transport ◽  
Genomic Structural Variation ◽  
Field Samples ◽  
The Impact

ABSTRACTThe Ascomycete fungusPhaeoacremonium minimumis one of the primary causal agents of Esca, a widespread and damaging grapevine trunk disease. Variation in virulence amongPm. minimumisolates has been reported, but the underlying genetic basis of the phenotypic variability remains unknown. The goal of this study was to characterize intraspecific genetic diversity and explore its potential impact on virulence functions associated with secondary metabolism, cellular transport, and cell wall decomposition. We generated a chromosome-scale genome assembly, using single molecule real-time sequencing, and resequenced the genomes and transcriptomes of multiple isolates to identify sequence and structural polymorphisms. Numerous insertion and deletion events were found for a total of about 1 Mbp in each isolate. Structural variation in this extremely gene dense genome frequently caused presence/absence polymorphisms of multiple adjacent genes, mostly belonging to biosynthetic clusters associated with secondary metabolism. Because of the observed intraspecific diversity in gene content due to structural variation we concluded that a transcriptome reference developed from a single isolate is insufficient to represent the virulence factor repertoire of the species. We therefore compiled a pan-transcriptome reference ofPm. minimumcomprising a non-redundant set of 15,245 protein-coding sequences. Using naturally infected field samples expressing Esca symptoms, we demonstrated that mapping of meta-transcriptomics data on a multi-species reference that included thePm. minimumpan-transcriptome allows the profiling of an expanded set of virulence factors, including variable genes associated with secondary metabolism and cellular transport.

scholarly journals Nanofluidics to Enhance Single Molecule DNA Imaging: Detecting Genomic Structural Variation in Humans

2014 ◽  
Vol 106 (2) ◽  
pp. 395a
Author(s):  
David L.V. Bauer ◽  
Rodolphe M. Marie ◽  
Jonas N. Pedersen ◽  
Kristian H. Rasmussen ◽  
Mohammed Yusuf ◽  
...  
Keyword(s):  
Single Molecule ◽  
Structural Variation ◽  
Genomic Structural Variation ◽  
Dna Imaging

scholarly journals Fine-scale characterization of genomic structural variation in the human genome reveals adaptive and biomedically relevant hotspots

2018 ◽  
Author(s):  
Yen-Lung Lin ◽  
Omer Gokcumen
Keyword(s):  
Human Genome ◽  
Structural Variation ◽  
De Novo ◽  
Balancing Selection ◽  
Gene Clusters ◽  
Small Subset ◽  
Genomic Structural Variation ◽  
Chromosomal Breaks ◽  
Scale Characterization ◽  
Nonallelic Homologous Recombination

AbstractGenomic structural variants (SVs) are distributed nonrandomly across the human genome. These “hotspots” have been implicated in critical evolutionary innovations, as well as serious medical conditions. However, the evolutionary and biomedical features of these hotspots remain incompletely understood. In this study, we analyzed data from 2,504 genomes from the 1000 Genomes Project Consortium and constructed a refined map of 1,148 SV hotspots in human genomes. By studying the genomic architecture of these hotspots, we found that both nonallelic homologous recombination and non-homologous mechanisms act as mechanistic drivers of SV formation. We found that the majority of SV hotspots are within gene-poor regions and evolve under relaxed negative selection or neutrality. However, we found that a small subset of SV hotspots harbor genes that are enriched for anthropologically crucial functions, including blood oxygen transport, olfaction, synapse assembly, and antigen binding. We provide evidence that balancing selection may have maintained these SV hotspots, which include two independent hotspots on different chromosomes affecting alpha and beta hemoglobin gene clusters. Biomedically, we found that the SV hotspots coincide with breakpoints of clinically relevant, large de novo SVs, significantly more often than genome-wide expectations. As an example, we showed that the breakpoints of multiple large de novo SVs, which lead to idiopathic short stature, coincide with SV hotspots. As such, the mutational instability in SV hotpots likely enables chromosomal breaks that lead to pathogenic structural variation formations. Our study contributes to a better understanding of the mutational landscape of the genome and implicates both mechanistic and adaptive forces in the formation and maintenance of SV hotspots.

scholarly journals The impact of genomic structural variation on the transcriptome, chromatin, and proteome in the human brain

2021 ◽  
Author(s):  
Ricardo A Vialle ◽  
Katia de Paiva Lopes ◽  
David A Bennett ◽  
John F Crary ◽  
Towfique Raj
Keyword(s):  
Human Brain ◽  
Structural Variation ◽  
Brain Regions ◽  
Cis Acting ◽  
Genomic Structural Variation ◽  
Protein Levels ◽  
Post Mortem Brain ◽  
Whole Genomes ◽  
The Impact ◽  
The Brain

Structural variants (SVs), defined as any genomic rearrangements of 50 or more bp, are an important source of genetic diversity and have been linked to many diseases. However, their contribution to molecular traits in the brain and impact on neurodegenerative diseases remains unknown. Here, we report 170,996 SVs which were constructed using 1,760 short-read whole genomes from aging and Alzheimer's disease subjects. We quantified the impact of cis-acting SVs on several molecular traits including histone modification, gene expression, mRNA splicing, and protein abundance in post-mortem brain tissues. More than 3,800 genes were associated with at least one molecular phenotype, and 712 (18%) with more than one phenotype, with a significant positive correlation in the direction of effect between RNA, histone peaks, and protein levels. SV associations with RNA and protein levels shared the same direction of effect in more than 87% of SV-gene pairs. We found reproducibility of SV-eQTLs across three groups of samples and multiple brain regions ranging from 81 to 98%, including the innate immune system related genes ERAP2 and GBP3. Additionally, associations of SVs with progressive supranuclear palsy, an amyloid-independent primary tauopathy, identified previously known and novel SVs at the 17q.21.31 MAPT locus and several other novel suggestive associations. Our study provides a comprehensive view of the mechanisms linking structural variation to gene regulation and provides a valuable resource for understanding the functional impact of SVs in the aged human brain.

Mechanically-Tunable Quantum Interference in Ferrocene-Based Single-Molecule Junctions

2020 ◽  
Author(s):  
María Camarasa-Gómez ◽  
Daniel Hernangómez-Pérez ◽  
Michael S. Inkpen ◽  
Giacomo Lovat ◽  
E-Dean Fung ◽  
...  
Keyword(s):  
Single Molecule ◽  
Quantum Interference ◽  
Degrees Of Freedom ◽  
Building Blocks ◽  
Ferrocene Derivative ◽  
Single Molecule Junctions ◽  
Molecule Junction ◽  
Single Molecule Junction ◽  
The Impact ◽  
D Orbitals

Ferrocenes are ubiquitous organometallic building blocks that comprise a Fe atom sandwiched between two cyclopentadienyl (Cp) rings that rotate freely at room temperature. Of widespread interest in fundamental studies and real-world applications, they have also attracted<br>some interest as functional elements of molecular-scale devices. Here we investigate the impact of<br>the configurational degrees of freedom of a ferrocene derivative on its single-molecule junction<br>conductance. Measurements indicate that the conductance of the ferrocene derivative, which is<br>suppressed by two orders of magnitude as compared to a fully conjugated analog, can be modulated<br>by altering the junction configuration. Ab initio transport calculations show that the low conductance is a consequence of destructive quantum interference effects that arise from the hybridization of metal-based d-orbitals and the ligand-based π-system. By rotating the Cp rings, the hybridization, and thus the quantum interference, can be mechanically controlled, resulting in a conductance modulation that is seen experimentally.<br>

Monitoring the Structural Dynamics of U2 snRNA Via Single-Molecule Förster Resonance Energy Transfer

2018 ◽  
Author(s):  
Alexander Carl DeHaven
Keyword(s):  
Energy Transfer ◽  
Structural Dynamics ◽  
Single Molecule ◽  
Conformational Dynamics ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Förster Resonance Energy Transfer ◽  
U2 Snrna ◽  
Folding Dynamics ◽  
The Impact

This thesis contains four topic areas: a review of single-molecule microscropy methods and splicing, conformational dynamics of stem II of the U2 snRNA, the impact of post-transcriptional modifications on U2 snRNA folding dynamics, and preliminary findings on Mango aptamer folding dynamics.

scholarly journals A role for the fusogen eff-1 in epidermal stem cell number robustness in Caenorhabditis elegans

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sneha L. Koneru ◽  
Fu Xiang Quah ◽  
Ritobrata Ghose ◽  
Mark Hintze ◽  
Nicola Gritti ◽  
...  
Keyword(s):  
Stem Cell ◽  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Single Molecule ◽  
Phenotypic Variability ◽  
Low Frequency ◽  
Time Lapse ◽  
Cell Number ◽  
Seam Cell ◽  
Neuronal Tissues

AbstractDevelopmental patterning in Caenorhabditis elegans is known to proceed in a highly stereotypical manner, which raises the question of how developmental robustness is achieved despite the inevitable stochastic noise. We focus here on a population of epidermal cells, the seam cells, which show stem cell-like behaviour and divide symmetrically and asymmetrically over post-embryonic development to generate epidermal and neuronal tissues. We have conducted a mutagenesis screen to identify mutants that introduce phenotypic variability in the normally invariant seam cell population. We report here that a null mutation in the fusogen eff-1 increases seam cell number variability. Using time-lapse microscopy and single molecule fluorescence hybridisation, we find that seam cell division and differentiation patterns are mostly unperturbed in eff-1 mutants, indicating that cell fusion is uncoupled from the cell differentiation programme. Nevertheless, seam cell losses due to the inappropriate differentiation of both daughter cells following division, as well as seam cell gains through symmetric divisions towards the seam cell fate were observed at low frequency. We show that these stochastic errors likely arise through accumulation of defects interrupting the continuity of the seam and changing seam cell shape, highlighting the role of tissue homeostasis in suppressing phenotypic variability during development.

scholarly journals Genomic Characteristics and Comparative Genomics Analysis of Two Chinese Corynespora cassiicola Strains Causing Corynespora Leaf Fall (CLF) Disease

2021 ◽  
Vol 7 (6) ◽  
pp. 485
Author(s):  
Boxun Li ◽  
Yang Yang ◽  
Jimiao Cai ◽  
Xianbao Liu ◽  
Tao Shi ◽  
...  
Keyword(s):  
Comparative Genomics ◽  
Single Molecule ◽  
Rubber Tree ◽  
Gene Families ◽  
Gene Clusters ◽  
The Philippines ◽  
Tree Plantations ◽  
Comparative Genomic ◽  
Corynespora Cassiicola ◽  
Leaf Fall

Rubber tree Corynespora leaf fall (CLF) disease, caused by the fungus Corynespora cassiicola, is one of the most damaging diseases in rubber tree plantations in Asia and Africa, and this disease also threatens rubber nurseries and young rubber plantations in China. C. cassiicola isolates display high genetic diversity, and virulence profiles vary significantly depending on cultivar. Although one phytotoxin (cassicolin) has been identified, it cannot fully explain the diversity in pathogenicity between C. cassiicola species, and some virulent C. cassiicola strains do not contain the cassiicolin gene. In the present study, we report high-quality gapless genome sequences, obtained using short-read sequencing and single-molecule long-read sequencing, of two Chinese C. cassiicola virulent strains. Comparative genomics of gene families in these two stains and a virulent CPP strain from the Philippines showed that all three strains experienced different selective pressures, and metabolism-related gene families vary between the strains. Secreted protein analysis indicated that the quantities of secreted cell wall-degrading enzymes were correlated with pathogenesis, and the most aggressive CCP strain (cassiicolin toxin type 1) encoded 27.34% and 39.74% more secreted carbohydrate-active enzymes (CAZymes) than Chinese strains YN49 and CC01, respectively, both of which can only infect rubber tree saplings. The results of antiSMASH analysis showed that all three strains encode ~60 secondary metabolite biosynthesis gene clusters (SM BGCs). Phylogenomic and domain structure analyses of core synthesis genes, together with synteny analysis of polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) gene clusters, revealed diversity in the distribution of SM BGCs between strains, as well as SM polymorphisms, which may play an important role in pathogenic progress. The results expand our understanding of the C. cassiicola genome. Further comparative genomic analysis indicates that secreted CAZymes and SMs may influence pathogenicity in rubber tree plantations. The findings facilitate future exploration of the molecular pathogenic mechanism of C. cassiicola.

Genomic structural variation contributes to phenotypic change of industrial bioethanol yeastSaccharomyces cerevisiae

2016 ◽  
Vol 16 (2) ◽  
pp. fov118 ◽  
Author(s):  
Ke Zhang ◽  
Li-Jie Zhang ◽  
Ya-Hong Fang ◽  
Xin-Na Jin ◽  
Lei Qi ◽  
...  
Keyword(s):  
Structural Variation ◽  
Phenotypic Change ◽  
Genomic Structural Variation

scholarly journals Integrated Genomic Analysis of Sézary Syndrome

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Xin Mao ◽  
Tracy Chaplin ◽  
Bryan D. Young
Keyword(s):  
Copy Number ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Genomic Analysis ◽  
Gene Clusters ◽  
Sézary Syndrome ◽  
Sezary Syndrome ◽  
Snp Microarray ◽  
The Impact ◽  
Chromosome Regions

Sézary syndrome (SS) is a rare variant of primary cutaneous T-cell lymphoma. Little is known about the underlying pathogenesis of S. To address this issue, we used Affymetrix 10K SNP microarray to analyse 13 DNA samples isolated from 8 SS patients and qPCR with ABI TaqMan SNP genotyping assays for the validation of the SNP microarray results. In addition, we tested the impact of SNP loss of heterozygosity (LOH) identified in SS cases on the gene expression profiles of SS cases detected with Affymetrix GeneChip U133A. The results showed: (1) frequent SNP copy number change and LOH involving 1, 2p, 3, 4q, 5q, 6, 7p, 8, 9, 10, 11, 12q, 13, 14, 16q, 17, and 20, (2) reduced SNP copy number at FAT gene (4q35) in 75% of SS cases, and (3) the separation of all SS cases from normal control samples by SNP LOH gene clusters at chromosome regions of 9q31q34, 10p11q26, and 13q11q12. These findings provide some intriguing information for our current understanding of the molecular pathogenesis of this tumour and suggest the possibility of presence of functional SNP LOH in SS tumour cells.

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