scholarly journals Lentivirus Susceptibility in Iranian and German Sheep Assessed by Determination of TMEM154 E35K

Animals ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 685 ◽  
Author(s):  
Vahid Molaee ◽  
Vahid Otarod ◽  
Darab Abdollahi ◽  
Gesine Lühken
Keyword(s):  
Small Ruminant ◽  
Transmembrane Protein ◽  
Published Data ◽  
Brown Hair ◽  
Genome Wide ◽  
A Genome ◽  
Combining Data ◽  
First Time ◽  
Gwas Approach

Small ruminant lentiviruses (SRLVs) cause maedi-visna disease in sheep and are prevalent in Iran and Germany. The association of the transmembrane protein 154 (TMEM154) variants with SRLV infection has been previously identified by a genome-wide association (GWAS) approach and subsequent analyses, and validated in some US, German, and Turkish sheep flocks. We aimed at evaluating these findings for the first time in Iranian, and in some more German sheep flocks/breeds. Also, we aimed at comparing the SRLV susceptibility in Iranian and German sheep based on the frequency of the TMEM154 E35 allele. About 800 blood samples were collected from 21 Iranian and German sheep flocks/breeds for different purposes: (1) The association of TMEM154 E35K with SRLV infection status was tested in four sheep breeds and found to be significant in Kermani, Merinoland, and Brown Hair. (2) The usefulness of the TMEM154 E35 frequency for predicting SRLV susceptibility was evaluated by regression analysis, combining data from this study and some already published data. Results showed a significant association between E35 frequency and SRLV prevalence. (3) SRLV susceptibility was compared based on E35 frequency in Iranian and German sheep. Altogether, findings of this study provide valuable information on SRLV susceptibility, using TMEM154 E35, in Iranian and German sheep.

scholarly journals Genomic variation across a clinical Cryptococcus population linked to disease outcome

2021 ◽  
Author(s):  
Poppy Channa Sakti Sephton-Clark ◽  
Jennifer Tenor ◽  
Dena Toffaletti ◽  
Nancy Meyers ◽  
Charles Giamberardino ◽  
...  
Keyword(s):  
Patient Outcomes ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Sugar Transport ◽  
Genomic Variation ◽  
Clinical Isolates ◽  
Genome Wide ◽  
A Genome ◽  
Gwas Approach

Cryptococcus neoformans is the causative agent of cryptococcosis, a disease with poor patient outcomes, accounting for approximately 180,000 deaths each year. Patient outcomes may be impacted by the underlying genetics of the infecting isolate, however, our current understanding of how genetic diversity contributes to clinical outcomes is limited. Here, we leverage clinical, in vitro growth and genomic data for 284 C. neoformans isolates to identify clinically relevant pathogen variants within a population of clinical isolates from patients with HIV-associated cryptococcosis in Malawi. Through a genome-wide association study (GWAS) approach, we identify variants associated with fungal burden and growth rate. We also find both small and large-scale variation, including aneuploidy, associated with alternate growth phenotypes, which may impact the course of infection. Genes impacted by these variants are involved in transcriptional regulation, signal transduction, glycolysis, sugar transport, and glycosylation. When combined with clinical data, we show that growth within the CNS is reliant upon glycolysis in an animal model, and likely impacts patient mortality, as CNS burden modulates patient outcome. Additionally, we find genes with roles in sugar transport are under selection in the majority of these clinical isolates. Further, we demonstrate that two hypothetical proteins identified by GWAS impact virulence in animal models. Our approach illustrates links between genetic variation and clinically relevant phenotypes, shedding light on survival mechanisms within the CNS and pathways involved in this persistence.

scholarly journals A Genome-Wide Association Analysis Reveals a Role for Recombination in the Evolution of Antimicrobial Resistance in Burkholderia multivorans

2018 ◽  
Author(s):  
Julio Diaz Caballero ◽  
Shawn T. Clark ◽  
Pauline W. Wang ◽  
Sylva L. Donaldson ◽  
Bryan Coburn ◽  
...  
Keyword(s):  
Burkholderia Cepacia ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Mortality And Morbidity ◽  
Burkholderia Multivorans ◽  
Post Transplant ◽  
Genome Wide ◽  
A Genome ◽  
Genomic Study ◽  
Gwas Approach

AbstractCystic fibrosis (CF) lung infections caused by members of the Burkholderia cepacia complex, such as Burkholderia multivorans, are associated with high rates of mortality and morbidity. We performed a population genomic study of 111 B. multivorans sputum isolates from a single CF patient through three stages of infection including the initial incident infection, deep sampling of a one-year period of chronic infection, and deep sampling of a post-transplant recolonization. We reconstructed the evolutionary history of the population and used a lineage-controlled genome-wide association study (GWAS) approach to identify genetic variants associated with antibiotic resistance. We found that the incident isolate was more susceptible to agents from three antimicrobial classes (β-lactams, aminoglycosides, quinolones), while the chronic isolates diversified into distinct genetic lineages with reduced antimicrobial susceptibility to the same agents. The post-transplant reinfection isolates displayed genetic and phenotypic signatures that were distinct from sputum isolates from all CF lung specimens. There were numerous examples of parallel pathoadaptation, in which individual loci, or even the same codon, were independently mutated multiple times. This set of loci was enriched for functions associated with virulence and resistance. Our GWAS approach identified one variant in the ampD locus (which was independently mutated four times in our dataset) associated with resistance to β-lactams, and two non-synonymous polymorphisms associated with resistance to both aminoglycosides and quinolones, affecting an araC family transcriptional regulator, which was independently mutated three times, and an outer member porin, which was independently mutated twice. We also performed recombination analysis and identified a minimum of 14 recombination events. Parallel pathoadaptive loci and polymorphisms associated with β-lactam resistance were over-represented in these recombinogenic regions. This study illustrates the power of deep, longitudinal sampling coupled with evolutionary and lineage-corrected GWAS analyses to reveal how pathogens adapt to their hosts.

scholarly journals Epilepsy subtype-specific copy number burden observed in a genome-wide study of 17 458 subjects

Brain ◽  
2020 ◽  
Vol 143 (7) ◽  
pp. 2106-2118 ◽  
Author(s):  
Lisa-Marie Niestroj ◽  
Eduardo Perez-Palma ◽  
Daniel P Howrigan ◽  
Yadi Zhou ◽  
Feixiong Cheng ◽  
...  
Keyword(s):  
Copy Number ◽  
Focal Epilepsy ◽  
Copy Number Variants ◽  
Epileptic Encephalopathy ◽  
Human Interactome ◽  
Genome Wide ◽  
A Genome ◽  
Wide Scale ◽  
Generalized Epilepsy ◽  
First Time

Abstract Cytogenic testing is routinely applied in most neurological centres for severe paediatric epilepsies. However, which characteristics of copy number variants (CNVs) confer most epilepsy risk and which epilepsy subtypes carry the most CNV burden, have not been explored on a genome-wide scale. Here, we present the largest CNV investigation in epilepsy to date with 10 712 European epilepsy cases and 6746 ancestry-matched controls. Patients with genetic generalized epilepsy, lesional focal epilepsy, non-acquired focal epilepsy, and developmental and epileptic encephalopathy were included. All samples were processed with the same technology and analysis pipeline. All investigated epilepsy types, including lesional focal epilepsy patients, showed an increase in CNV burden in at least one tested category compared to controls. However, we observed striking differences in CNV burden across epilepsy types and investigated CNV categories. Genetic generalized epilepsy patients have the highest CNV burden in all categories tested, followed by developmental and epileptic encephalopathy patients. Both epilepsy types also show association for deletions covering genes intolerant for truncating variants. Genome-wide CNV breakpoint association showed not only significant loci for genetic generalized and developmental and epileptic encephalopathy patients but also for lesional focal epilepsy patients. With a 34-fold risk for developing genetic generalized epilepsy, we show for the first time that the established epilepsy-associated 15q13.3 deletion represents the strongest risk CNV for genetic generalized epilepsy across the whole genome. Using the human interactome, we examined the largest connected component of the genes overlapped by CNVs in the four epilepsy types. We observed that genetic generalized epilepsy and non-acquired focal epilepsy formed disease modules. In summary, we show that in all common epilepsy types, 1.5–3% of patients carry epilepsy-associated CNVs. The characteristics of risk CNVs vary tremendously across and within epilepsy types. Thus, we advocate genome-wide genomic testing to identify all disease-associated types of CNVs.

scholarly journals Whole Genome Sequencing of the Blue Tilapia (Oreochromis aureus) Provides a Valuable Genetic Resource for Biomedical Research on Tilapias

Marine Drugs ◽  
2019 ◽  
Vol 17 (7) ◽  
pp. 386 ◽  
Author(s):  
Chao Bian ◽  
Jia Li ◽  
Xueqiang Lin ◽  
Xiyang Chen ◽  
Yunhai Yi ◽  
...  
Keyword(s):  
Genome Assembly ◽  
Genetic Resource ◽  
Draft Genome ◽  
Close Relative ◽  
Protein Coding ◽  
Oreochromis Aureus ◽  
Genome Wide ◽  
A Genome ◽  
Blue Tilapia ◽  
First Time

Blue tilapia (Oreochromis aureus) has been an economically important fish in Asian countries. It can grow and reproduce in both freshwater and brackish water conditions, whereas it is also considered as a significant invasive species around the world. This species has been widely used as the hybridization parent(s) for tilapia breeding with a major aim to produce novel strains. However, available genomic resources are still limited for this important tilapia species. Here, we for the first time sequenced and assembled a draft genome for a seawater cultured blue tilapia (0.92 Gb), with 97.8% completeness and a scaffold N50 of 1.1 Mb, which suggests a relatively high quality of this genome assembly. We also predicted 23,117 protein-coding genes in the blue tilapia genome. Comparisons of predicted antimicrobial peptides between the blue tilapia and its close relative Nile tilapia proved that these immunological genes are highly similar with a genome-wide scattering distribution. As a valuable genetic resource, our blue tilapia genome assembly will benefit for biomedical researches and practical molecular breeding for high resistance to various diseases, which have been a critical problem in the aquaculture of tilapias.

A STUDY OF THE POPULATION GENOMIC STRUCTURE AND THE CHARACTER OF THE GENETIC DIVERGENCE OF EQUINE BREEDS (EQUUS CABALLUS L.)

2021 ◽  
Vol 1 (19) ◽  
pp. 335-338
Author(s):  
V.V. Kalashnikov ◽  
L.A. Khrabrova ◽  
N.V. Blokhina ◽  
T.V. Kalashnikova
Keyword(s):  
High Efficiency ◽  
Genomic Structure ◽  
Genome Wide Analysis ◽  
Horse Breeding ◽  
Population Genomic ◽  
Genome Wide ◽  
A Genome ◽  
Selected Traits ◽  
First Time ◽  
Genome Wide Study

For the first time, a genome-wide study was conducted for 6 native breeds (Kabardian, Vyatka, zabaikalian, Yakut) with unique adaptive qualities and 2 cultural breeds that are strictly selected for multidirectional characteristics. Data on the state of the genetic structure of breeds were obtained. The phylogenetic relationships between breeds were studied, the ancestral groups that participated in the formation of the breed structure were determined, and the influence of factory improver breeds on the microevolution of local breeds was estimated. the results of the research are correlated with the freely available results of the genome-wide analysis of foreign horse populations and breeds. The ways of identifying complexes that characterize the severity of selected traits in breeds with different directions of use are outlined. The high efficiency of using the obtained results to determine belonging to a particular breed is determined. A database of mitochondrial DNA and Y-chromosome haplotypes was created to conduct a retrospective analysis of the origin and refinement of breeding records in the system of centralized breeding records in horse breeding. As additional markers, we used targeted SNPs that characterize the severity of selected traits

A Genome-Wide RNAi Screen to Identify Novel Genes Involved in Clonal Maintenance of ALL

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2390-2390
Author(s):  
Frida Ponthan ◽  
Simon Bomken ◽  
Deepali Pal ◽  
Alex Elder ◽  
Hesta McNeill ◽  
...  
Keyword(s):  
Stem Cell ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Rnai Screen ◽  
Published Data ◽  
Shrna Expression ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Genome Wide ◽  
A Genome

Abstract Acute lymphoblastic leukemia (ALL) is the most common malignancy in children and adolescents where treatment is associated with significant morbidity. Novel therapeutic approaches to improve treatment outcome and minimize side-effects are therefore required. We have previously shown a lack of stem cell hierarchy and a high frequency of leukemic stem cells in ALL. Based on these findings, we have postulated that malignant self-renewal in ALL may be similar to lymphoid, but distinct from hematopoietic stem cell (HSC) self-renewal thereby providing new therapeutic targets for diseases affecting the lymphoid system. To identify targets and pathways involved in ALL self-renewal, we have performed a genome-wide RNAi screen in the ALL cell line SEM, which carries the translocation t(4;11) and expresses the MLL/AF4 fusion gene. SEM cells were lentivirally transduced using the Decode™ pGIPZ negative selection library consisting of 7 pools of 10,000 shRNA constructs each. The pGIPZ vector allows for Pol II-dependent shRNA expression, GFP-based cell sorting and selection for puromycin resistance. Self-renewal was addressed by replating of transduced cells on puromycin-resistant murine stromal bone marrow feeder cells (M2-10B4), which mimics a niche environment in vitro. SEM cells were selected with puromycin and seeded at low cellular-density under serum-starved conditions to ensure adherence-dependent growth. SEM cells were replated onto new feeders and the puromycin selective pressure was kept throughout the experiments to minimize silencing of shRNA expression. Cells were harvested after the second plating (F2, ~30 days after transduction) and the prevalence of shRNA constructs in F2 was compared to samples harvested 6 days after transduction (baseline, BL) using next generation sequencing of genomic DNA. Initial sequencing results obtained from one out of seven pools show that constructs targeting 637 different genes were differentially expressed (2 –fold change, padj <0.05). For instance, shRNAs targeting genes associated with lymphoid differentiation such as IKZF3 (B-cell progenitor differentiation) and CD20 (marker of B-cell differentiation) were enriched, whereas constructs targeting genes important for proliferation and survival such as BCL2 (survival), BRD4 (epigenetic reader, therapeutic target in leukemia), MAX (partner of MYC), BMI1 (polycomb complex 1 member, required for self-renewal) or POT1 (telomere integrity) were depleted. Furthermore, constructs targeting MAPK9/JNK2 and JUN in the mitogen-activated protein kinase pathway were depleted whilst the construct targeting DUSP10 (inhibitor of MAPK9/JNK2) was enriched, further proving that our screen has functional relevance within a biological context. Interestingly, the construct targeting the aryl hydrocarbon receptor (AHR) involved in B-cell maturation was also increased, which is in line with published data showing that inhibition of AHR drives stem cell maintenance. These results demonstrate the feasibility of our approach where we have established a robust screening protocol that can identify genes involved in survival and self-renewal. Sequencing data from the additional six pools are currently being analyzed. These analyses are expected to provide important information about the key mechanisms by which leukemic blasts maintain their “stemness” in ALL. Disclosures No relevant conflicts of interest to declare.

scholarly journals ChiRA: an integrated framework for chimeric read analysis from RNA-RNA interactome and RNA structurome data

GigaScience ◽  
2021 ◽  
Vol 10 (2) ◽  
Author(s):  
Pavankumar Videm ◽  
Anup Kumar ◽  
Oleg Zharkov ◽  
Björn Andreas Grüning ◽  
Rolf Backofen
Keyword(s):  
Rna Structure ◽  
Complete Analysis ◽  
Published Data ◽  
Random Choice ◽  
Sequencing Technologies ◽  
Genome Wide ◽  
A Genome ◽  
Interaction Partners ◽  
Rna Interaction ◽  
New Interactions

Abstract Background With the advances in next-generation sequencing technologies, it is possible to determine RNA-RNA interaction and RNA structure predictions on a genome-wide level. The reads from these experiments usually are chimeric, with each arm generated from one of the interaction partners. Owing to short read lengths, often these sequenced arms ambiguously map to multiple locations. Thus, inferring the origin of these can be quite complicated. Here we present ChiRA, a generic framework for sensitive annotation of these chimeric reads, which in turn can be used to predict the sequenced hybrids. Results Grouping reference loci on the basis of aligned common reads and quantification improved the handling of the multi-mapped reads in contrast to common strategies such as the selection of the longest hit or a random choice among all hits. On benchmark data ChiRA improved the number of correct alignments to the reference up to 3-fold. It is shown that the genes that belong to the common read loci share the same protein families or similar pathways. In published data, ChiRA could detect 3 times more new interactions compared to existing approaches. In addition, ChiRAViz can be used to visualize and filter large chimeric datasets intuitively. Conclusion ChiRA tool suite provides a complete analysis and visualization framework along with ready-to-use Galaxy workflows and tutorials for RNA-RNA interactome and structurome datasets. Common read loci built by ChiRA can rescue multi-mapped reads on paralogous genes without requiring any information on gene relations. We showed that ChiRA is sensitive in detecting new RNA-RNA interactions from published RNA-RNA interactome datasets.

The top skin-associated genes: a comparative analysis of human and mouse skin transcriptomes

2014 ◽  
Vol 395 (6) ◽  
pp. 577-591 ◽  
Author(s):  
Peter Arne Gerber ◽  
Bettina Alexandra Buhren ◽  
Holger Schrumpf ◽  
Bernhard Homey ◽  
Albert Zlotnik ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
Human Skin ◽  
Current Knowledge ◽  
Mouse Skin ◽  
Published Data ◽  
Healthy Human ◽  
Genome Wide ◽  
A Genome ◽  
Human And Mouse

Abstract The mouse represents a key model system for the study of the physiology and biochemistry of skin. Comparison of skin between mouse and human is critical for interpretation and application of data from mouse experiments to human disease. Here, we review the current knowledge on structure and immunology of mouse and human skin. Moreover, we present a systematic comparison of human and mouse skin transcriptomes. To this end, we have recently used a genome-wide database of human gene expression to identify genes highly expressed in skin, with no, or limited expression elsewhere – human skin-associated genes (hSAGs). Analysis of our set of hSAGs allowed us to generate a comprehensive molecular characterization of healthy human skin. Here, we used a similar database to generate a list of mouse skin-associated genes (mSAGs). A comparative analysis between the top human (n=666) and mouse (n=873) skin-associated genes (SAGs) revealed a total of only 30.2% identity between the two lists. The majority of shared genes encode proteins that participate in structural and barrier functions. Analysis of the top functional annotation terms revealed an overlap for morphogenesis, cell adhesion, structure, and signal transduction. The results of this analysis, discussed in the context of published data, illustrate the diversity between the molecular make up of skin of both species and grants a probable explanation, why results generated in murine in vivo models often fail to translate into the human.

scholarly journals Genome-wide Association Study identifies two novel loci for Gilles de la Tourette Syndrome

2021 ◽  
Author(s):  
Fotis Tsetsos ◽  
Apostolia Topaloudi ◽  
Pritesh Jain ◽  
Zhiyu Yang ◽  
Dongmei Yu ◽  
...  
Keyword(s):  
Tourette Syndrome ◽  
Genome Wide Association Study ◽  
Neurodevelopmental Disorder ◽  
Published Data ◽  
Volume Data ◽  
Polygenic Risk ◽  
Genome Wide ◽  
A Genome ◽  
Risk Scoring ◽  
Significant Locus

Tourette Syndrome (TS) is a childhood-onset neurodevelopmental disorder of complex genetic architecture, characterized by multiple motor tics and at least one vocal tic persisting for more than one year. We performed a genome-wide meta-analysis integrating a novel TS cohort with previously published data, resulting in a sample size of 6,133 TS individuals and 13,565 ancestry-matched controls. We identified a genome-wide significant locus on chromosome 5q15 and one array-wide significant locus on chromosome 2q24.2. Integration of eQTL, Hi-C and GWAS data implicated the NR2F1 gene and associated lncRNAs within the 5q15 locus, and the RBMS1 gene within the 2q24.2 locus. Polygenic risk scoring using previous GWAS results demonstrated statistically significant ability to predict TS status in the novel cohort. Heritability partitioning identified statistically significant enrichment in brain tissue histone marks, while polygenic risk scoring on brain volume data identified statistically significant associations with right and left putamen volumes. Our work presents novel insights in the neurobiology of TS opening up new directions for future studies.

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