Comparative genomic analysis of non-coding sequences and the application of RNA interference tools for bovine functional genomics

2005 ◽  
Vol 45 (8) ◽  
pp. 995 ◽  
Author(s):  
A. E. Lew ◽  
L. A. Jackson ◽  
M. I. Bellgard
Keyword(s):  
Rna Interference ◽  
Protein Translation ◽  
Current Status ◽  
Parasitic Infections ◽  
Comparative Genomic ◽  
Specific Gene ◽  
Coding Sequences ◽  
Mrna Targets ◽  
Mouth Disease Virus ◽  
Immune Pathways

Non-coding (nc) RNAs are important regulators of developmental genes, and essential for the modification of cellular DNA and chromatin through a process known as RNA interference (RNAi). The mediators of RNAi can be in the form of short double stranded (ds) RNAs, micro (mi) RNAs or small interfering (si) RNAs. miRNAs are involved in a translation repression pathway that inhibits protein translation in mRNA targets. Comparative genomic screens have revealed conserved regulatory non-coding sequences, which assist to predict the function of endogenous miRNAs. Only a few comparative studies include bovine genomic sequence, and RNAi has yet to be applied in bovine genome functional screens. siRNAs target homologous mRNAs for degradation, and thereby, silence specific genes. The use of synthetic siRNAs facilitates the elucidation of gene pathways by specific gene knockdown. A survey of the literature identifies a small number of reports using RNAi to examine immune pathways in bovine cell lines; however, they do not target genes involved in specific production traits. Applications of RNAi to elucidate bovine immune pathways for relevant bacterial and parasite diseases are yet to be reported. The inhibition of viral replication using RNAi has been demonstrated with bovine RNA viruses such as pestivirus and foot and mouth disease virus signifying the potential of RNAi as an antiviral therapeutic. RNAi approaches combined with genome data for protozoan parasites, insects and nematodes, will expedite the identification of novel targets for the treatment and prevention of economically important parasitic infections. This review will examine the approaches used in mammalian RNAi research, the current status of its applications to livestock systems and will discuss potential applications in beef cattle programs.

scholarly journals Current Status and Potential of RNA Interference for the Management of Tomato Spotted Wilt Virus and Thrips Vectors

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 320
Author(s):  
Alexander Nilon ◽  
Karl Robinson ◽  
Hanu R. Pappu ◽  
Neena Mitter
Keyword(s):  
Rna Interference ◽  
Tomato Spotted Wilt Virus ◽  
Cultural Practices ◽  
Management Strategies ◽  
Current Status ◽  
Horticultural Crops ◽  
Yield And Quality ◽  
Tomato Spotted Wilt ◽  
Wilt Virus

Tomato spotted wilt virus (TSWV) is the type member of the genus Orthotospovirus in the family Tospoviridae and order Bunyavirales. TSWV, transmitted by several species of thrips, causes significant disease losses to agronomic and horticultural crops worldwide, impacting both the yield and quality of the produce. Management strategies include growing virus-resistant cultivars, cultural practices, and managing thrips vectors through pesticide application. However, numerous studies have reported that TSWV isolates can overcome host-plant resistance, while thrips are developing resistance to pesticides that were once effective. RNA interference (RNAi) offers a means of host defence by using double-stranded (ds) RNA to initiate gene silencing against invading viruses. However, adoption of this approach requires production and use of transgenic plants and thus limits the practical application of RNAi against TSWV and other viruses. To fully utilize the potential of RNAi for virus management at the field level, new and novel approaches are needed. In this review, we summarize RNAi and highlight the potential of topical or exogenous application of RNAi triggers for managing TSWV and thrips vectors.

Current status of soil-transmitted helminthiases among pre-school and school-aged children from Ile-Ife, Osun State, Nigeria

2010 ◽  
Vol 85 (3) ◽  
pp. 234-238 ◽  
Author(s):  
O.A. Sowemimo ◽  
S.O. Asaolu
Keyword(s):  
Private Schools ◽  
Private School ◽  
Primary Schools ◽  
Current Status ◽  
Parasitic Infections ◽  
Government Schools ◽  
Government School ◽  
Soil Transmitted Helminths ◽  
School Aged Children ◽  
Stool Samples

AbstractA cross-sectional survey was conducted to determine the prevalence and intensity of soil-transmitted helminths among pre-school and school-aged children attending nursery and primary schools in Ile-Ife. Single stool samples were collected between January and March, 2009 from 352 children randomly selected from a total of 456 children attending both private and government schools. The stool samples were processed using the modified Kato–Katz technique, and then examined for the eggs of soil-transmitted helminths (STHs). One hundred and twenty-one (34.4%) samples were positive for STH eggs. The overall prevalences of Ascaris lumbricoides, Trichuris trichiura and hookworm were 33.2%, 3.7% and 0.9%, respectively. The prevalence of STH infection in government schools (47.8%) was significantly higher than in private schools (16.1%) (P < 0.001). The most common type of mixed infection was the combination of A. lumbricoides and T. trichiura (6.8%). The prevalence and intensity of A. lumbricoides rose with age. The lowest prevalence and intensity (7.7%; 0.240 ± 0.136 eggs per gram (epg)) were recorded in the 2- to 3-year-old age group, while the highest prevalence and intensity (58.7%; 1.820 ± 0.237 epg) were recorded in children aged 10 years and above. A questionnaire survey indicated that 73% of the children attending private school had been treated with anthelminthics less than 2 months prior to the collection of stool specimens, while 43% of the children attending government school received anthelminthic treatment during the same period. The findings indicate that STH infections are endemic among schoolchildren in Ile-Ife and that the burden of parasitic infections is greater in government schools than in private schools.

Molecular Diagnostics in Melanoma: Current Status and Perspectives

2011 ◽  
Vol 135 (7) ◽  
pp. 860-869 ◽  
Author(s):  
Soheil S. Dadras
Keyword(s):  
Molecular Diagnostics ◽  
Ribonucleic Acid ◽  
New Technologies ◽  
Mutational Analysis ◽  
Transcriptional Profiling ◽  
Clinical Information ◽  
Current Status ◽  
Comparative Genomic ◽  
Molecular Approaches ◽  
Fresh Frozen

Abstract Context.—In the current “molecular” era, the advent of technology, such as array-based platforms, systems biology, and genome-wide approaches, has made it possible to examine human cancers, including melanoma, for genetic mutations, deletions, amplification, differentially regulated genes, and epigenetic changes. Advancement in current technologies is such that one can now examine ribonucleic acid (RNA), deoxyribonucleic acid (DNA), and protein directly from the patient's own tumor. Objective.—To apply these new technologies in advancing molecular diagnostics in melanoma has historically suffered from a major obstacle, namely, the scarcity of fresh frozen, morphologically defined tumor banks, annotated with clinical information. Recently, some of the new platforms have advanced to permit utilization of formalin-fixed, paraffin-embedded (FFPE) tumor specimens as starting material. Data Sources.—This article reviews the latest technologies applied to FFPE melanoma sections, narrowing its focus on the utility of transcriptional profiling, especially for melastatin; comparative genomic hybridization; BRAF and NRAS mutational analysis; and micro ribonucleic acid profiling. Conclusion.—New molecular approaches are emerging and are likely to improve the classification of melanocytic neoplasms.

Advances in Specific Gene Knockdown of Therapeutic Targets by RNA Interference

2018 ◽  
Vol 24 (23) ◽  
pp. 2631-2631
Author(s):  
Fabiola Garcia Praça ◽  
Maria Vitória Lopes Badra Bentley
Keyword(s):  
Rna Interference ◽  
Therapeutic Targets ◽  
Gene Knockdown ◽  
Specific Gene

scholarly journals Genetic Validation of Leishmania donovani Lysyl-tRNA Synthetase Shows that It Is Indispensable for Parasite Growth and Infectivity

mSphere ◽  
2017 ◽  
Vol 2 (4) ◽  
Author(s):  
Sanya Chadha ◽  
N. Arjunreddy Mallampudi ◽  
Debendra K. Mohapatra ◽  
Rentala Madhubala
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Essential Gene ◽  
Protozoan Parasite ◽  
Protein Translation ◽  
Trna Synthetase ◽  
Parasite Growth ◽  
Coding Sequences ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases

ABSTRACT Leishmania donovani is a protozoan parasite that causes visceral leishmaniasis. Increasing resistance and severe side effects of existing drugs have led to the need to identify new chemotherapeutic targets. Aminoacyl-tRNA synthetases (aaRSs) are ubiquitous and are required for protein synthesis. aaRSs are known drug targets for bacterial and fungal pathogens. Here, we have characterized and evaluated the essentiality of L. donovani lysyl-tRNA synthetase (LdLysRS). Two different coding sequences for lysyl-tRNA synthetases are annotated in the Leishmania genome database. LdLysRS-1 (LdBPK_150270.1), located on chromosome 15, is closer to apicomplexans and eukaryotes, whereas LdLysRS-2 (LdBPK_300130.1), present on chromosome 30, is closer to bacteria. In the present study, we have characterized LdLysRS-1. Recombinant LdLysRS-1 displayed aminoacylation activity, and the protein localized to the cytosol. The LdLysRS-1 heterozygous mutants had a restrictive growth phenotype and attenuated infectivity. LdLysRS-1 appears to be an essential gene, as a chromosomal knockout of LdLysRS-1 could be generated when the gene was provided on a rescuing plasmid. Cladosporin, a fungal secondary metabolite and a known inhibitor of LysRS, was more potent against promastigotes (50% inhibitory concentration [IC50], 4.19 µM) and intracellular amastigotes (IC50, 1.09 µM) than were isomers of cladosporin (3-epi-isocladosporin and isocladosporin). These compounds exhibited low toxicity to mammalian cells. The specificity of inhibition of parasite growth caused by these inhibitors was further assessed using LdLysRS-1 heterozygous mutant strains and rescue mutant promastigotes. These inhibitors inhibited the aminoacylation activity of recombinant LdLysRS. Our data provide a framework for the development of a new class of drugs against this parasite. IMPORTANCE Aminoacyl-tRNA synthetases are housekeeping enzymes essential for protein translation, providing charged tRNAs for the proper construction of peptide chains. These enzymes provide raw materials for protein translation and also ensure fidelity of translation. L. donovani is a protozoan parasite that causes visceral leishmaniasis. It is a continuously proliferating parasite that depends heavily on efficient protein translation. Lysyl-tRNA synthetase is one of the aaRSs which charges lysine to its cognate tRNA. Two different coding sequences for lysyl-tRNA synthetases (LdLysRS) are present in this parasite. LdLysRS-1 is closer to apicomplexans and eukaryotes, whereas LdLysRS-2 is closer to bacteria. Here, we have characterized LdLysRS-1 of L. donovani. LdLysRS-1 appears to be an essential gene, as the chromosomal null mutants did not survive. The heterozygous mutants showed slower growth kinetics and exhibited attenuated virulence. This study also provides a platform to explore LdLysRS-1 as a potential drug target.

scholarly journals Novel start codons introduce novel coding sequences in the human genomes

2020 ◽  
Author(s):  
He Zhang ◽  
Yang Xie
Keyword(s):  
Translation Initiation ◽  
Genomic Analysis ◽  
Comparative Genomic ◽  
Human Populations ◽  
The Novel ◽  
Coding Sequences ◽  
Human Genomes ◽  
High Level ◽  
Selection Signal ◽  
Human Specific

AbstractStart-gain mutations can introduce novel start codons and generate novel coding sequences that may affect the function of genes. In this study, we systematically investigated the novel start codons that were either polymorphic or fixed in the human genomes. 829 polymorphic start-gain SNVs were identified in the human populations, and the novel start codons introduced by these SNVs have significantly higher activity in translation initiation. Some of these start-gain SNVs were reported to be associated with phenotypes and diseases in previous studies. By comparative genomic analysis, we found 26 human-specific start codons that were fixed after the divergence between the human and chimpanzee, and high-level translation initiation activity was observed on them. The negative selection signal was detected in the novel coding sequences introduced by these human-specific start codons, indicating the important function of these novel coding sequences. This study reveals start-gain mutations are keeping appearing in the human genomes during the evolution and may be important sources altering the function of genes which may further affect the phenotypes or cause diseases.

scholarly journals Comparative genomic analysis of eutherian connexin genes

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Marko Premzl
Keyword(s):  
Genomic Analysis ◽  
Comparative Genomic Analysis ◽  
Comparative Genomic ◽  
Data Sets ◽  
Data Set ◽  
Coding Sequences ◽  
Gene Annotations ◽  
Connexin Gene ◽  
Connexin Genes ◽  
Gene Data

AbstractThe eutherian connexins were characterized as protein constituents of gap junctions implicated in cell-cell communications between adjoining cells in multiple cell types, regulation of major physiological processes and disease pathogeneses. However, conventional connexin gene and protein classifications could be regarded as unsuitable in descriptions of comprehensive eutherian connexin gene data sets, due to ambiguities and inconsistencies in connexin gene and protein nomenclatures. Using eutherian comparative genomic analysis protocol and 35 public eutherian reference genomic sequence data sets, the present analysis attempted to update and revise comprehensive eutherian connexin gene data sets, and address and resolve major discrepancies in their descriptions. Among 631 potential coding sequences, the tests of reliability of eutherian public genomic sequences annotated, in aggregate, 349 connexin complete coding sequences. The most comprehensive curated eutherian connexin gene data set described 21 major gene clusters, 4 of which included evidence of differential gene expansions. For example, the present gene annotations initially described human CXNK1 gene and annotated 22 human connexin genes. Phylogenetic tree calculations and calculations of pairwise nucleotide sequence identity patterns proposed revised and updated phylogenetic classification of eutherian connexin genes. Therefore, the present study integrating gene annotations, phylogenetic analysis and protein molecular evolution analysis proposed new nomenclature of eutherian connexin genes and proteins.

scholarly journals Comparative Genomics of Escherichia coli Strains Causing Urinary Tract Infections

2011 ◽  
Vol 77 (10) ◽  
pp. 3268-3278 ◽  
Author(s):  
Rebecca Munk Vejborg ◽  
Viktoria Hancock ◽  
Mark A. Schembri ◽  
Per Klemm
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Asymptomatic Bacteriuria ◽  
Genomic Islands ◽  
Comparative Genomic ◽  
Specific Gene ◽  
Virulence Determinants ◽  
Content Type ◽  
Tract Infections

ABSTRACTThe virulence determinants of uropathogenicEscherichia colihave been studied extensively over the years, but relatively little is known about what differentiates isolates causing various types of urinary tract infections. In this study, we compared the genomic profiles of 45 strains from a range of different clinical backgrounds, i.e., urosepsis, pyelonephritis, cystitis, and asymptomatic bacteriuria (ABU), using comparative genomic hybridization analysis. A microarray based on 31 completeE. colisequences was used. It emerged that there is little correlation between the genotypes of the strains and their disease categories but strong correlation between the genotype and the phylogenetic group association. Also, very few genetic differences may exist between isolates causing symptomatic and asymptomatic infections. Only relatively few genes that could potentially differentiate between the individual disease categories were identified. Among these were two genomic islands, namely, pathogenicity island (PAI)-CFT073-serUand PAI-CFT073-pheU, which were significantly more associated with the pyelonephritis and urosepsis isolates than with the ABU and cystitis isolates. These two islands harbor genes encoding virulence factors, such as P fimbriae (pyelonephritis-associated fimbriae) and an important immunomodulatory protein, TcpC. It seems that both urovirulence and growth fitness can be attributed to an assortment of genes rather than to a specific gene set. Taken together, urovirulence and fitness are the results of the interplay of a mixture of factors taken from a rich menu of genes.

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