Nucleocapsid mutations in SARS-CoV-2 augment replication and pathogenesis.

While SARS-CoV-2 continues to adapt for human infection and transmission, genetic variation outside of the spike gene remains largely unexplored. This study investigates a highly variable region at residues 203-205 in SARS-CoV-2 nucleocapsid protein. Recreating the alpha variant mutation in an early pandemic (WA-1) background, we found that the R203K-G204R mutation is sufficient to enhance replication, fitness, and pathogenesis of SARS-CoV-2. Importantly, the R203K-G204R mutation increases nucleocapsid phosphorylation, providing a molecular basis for these phenotypes. Notably, an analogous alanine substitution mutant also increases SARS-CoV-2 fitness and phosphorylation, suggesting that infection is enhanced through ablation of the ancestral RG motif. Overall, these results demonstrate that variant mutations outside spike are also key components in SARS-CoV-2 continued adaptation to human infection.

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Loci, genes, and gene networks associated with life history variation in a model ecological organism,Daphnia pulex(complex)

10.1101/436733 ◽

2018 ◽

Author(s):

Jacob W. Malcom ◽

Thomas E. Juenger ◽

Mathew A. Leibold

Keyword(s):

Gene Expression ◽

Genetic Variation ◽

Life History ◽

Molecular Basis ◽

Life History Traits ◽

Evolutionary Dynamics ◽

Daphnia Pulex ◽

Life History Trait ◽

Life History Variation ◽

Trait Variation

ABSTRACTBackgroundIdentifying the molecular basis of heritable variation provides insight into the underlying mechanisms generating phenotypic variation and the evolutionary history of organismal traits. Life history trait variation is of central importance to ecological and evolutionary dynamics, and contemporary genomic tools permit studies of the basis of this variation in non-genetic model organisms. We used high density genotyping, RNA-Seq gene expression assays, and detailed phenotyping of fourteen ecologically important life history traits in a wild-caught panel of 32Daphnia pulexclones to explore the molecular basis of trait variation in a model ecological species.ResultsWe found extensive phenotypic and a range of heritable genetic variation (~0 < H2< 0.44) in the panel, and accordingly identify 75-261 genes—organized in 3-6 coexpression modules—associated with genetic variation in each trait. The trait-related coexpression modules possess well-supported promoter motifs, and in conjunction with marker variation at trans- loci, suggest a relatively small number of important expression regulators. We further identify a candidate genetic network with SNPs in eight known transcriptional regulators, and dozens of differentially expressed genes, associated with life history variation. The gene-trait associations include numerous un-annotated genes, but also support several a priori hypotheses, including an ecdysone-induced protein and several Gene Ontology pathways.ConclusionThe genetic and gene expression architecture ofDaphnialife history traits is complex, and our results provide numerous candidate loci, genes, and coexpression modules to be tested as the molecular mechanisms that underlieDaphniaeco-evolutionary dynamics.

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Molecular Basis of Genetic Variation of Viruses

Virus as Populations ◽

10.1016/b978-0-12-800837-9.00002-2 ◽

2016 ◽

pp. 35-71 ◽

Cited By ~ 3

Author(s):

Esteban Domingo

Keyword(s):

Genetic Variation ◽

Molecular Basis

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Finding the molecular basis of complex genetic variation in humans and mice

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2005.1798 ◽

2006 ◽

Vol 361 (1467) ◽

pp. 393-401 ◽

Cited By ~ 13

Author(s):

Richard Mott

Keyword(s):

Genetic Variation ◽

Association Mapping ◽

Molecular Basis ◽

State Of The Art ◽

Complex Trait ◽

The State ◽

Rodent Model ◽

Model Systems ◽

Trait Analysis

I survey the state of the art in complex trait analysis, including the use of new experimental and computational technologies and resources becoming available, and the challenges facing us. I also discuss how the prospects of rodent model systems compare with association mapping in humans.

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An Application of Molecular Tools in Plant Genetic Diversity Conservation

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.955-959.830 ◽

2014 ◽

Vol 955-959 ◽

pp. 830-833

Author(s):

Zhou Xuan ◽

Zheng Hong Li ◽

Cheng Zhang ◽

Hong Dao Zhang ◽

Ji Lin Li ◽

...

Keyword(s):

Genetic Diversity ◽

Sustainable Development ◽

Genetic Variation ◽

Molecular Markers ◽

Poverty Alleviation ◽

Molecular Basis ◽

Species Boundaries ◽

Molecular Tools ◽

New Techniques ◽

Forestry Production

The conservation and use of plant genetic diversity are essential to the continued maintenance and improvement of agricultural and forestry production and thus, to sustainable development and poverty alleviation. The dramatic advances in molecular genetics over the last decade years have provided workers involved in the conservation of plant genetic diversity with a range of new techniques. Molecular tools, such as molecular markers and other genomic applications, have been highly successful in characterizing existing genetic variation within species, which generates new genetic diversity that often extends beyond species boundaries. The objectives of this article are to review the molecular basis on plant genetic diversity conservation and summarize the continuously rising and application of molecular tool. Then, we look forward and consider the significant of application of molecular tools in plant genetic diversity conservation.

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High Rate of Circulating MERS-CoV in Dromedary Camels at Slaughterhouses in Riyadh, 2019

10.20944/preprints202009.0324.v1 ◽

2020 ◽

Author(s):

Taibh Aljasim ◽

Abdulrahman Almasoud ◽

Haya A. Aljami ◽

Mohamed W. Alenazi ◽

Suliman A. Alsagaby ◽

...

Keyword(s):

Saudi Arabia ◽

Vaccine Development ◽

Sequence Similarity ◽

Rapid Test ◽

Respiratory Illness ◽

Human Infection ◽

High Rate ◽

Serum Samples ◽

Spike Gene ◽

Nasal Swabs

Background: MERS-CoV is a zoonotic virus that have emerged in humans in 2012 and caused severe respiratory illness with mortality rate of 34.4%. Since its appearance, MERS-CoV have been reported in 27 countries and most of these cases were in Saudi Arabia. So far, dromedaries are considered to be the intermediate host and the only known source of human infection. Method: This study was designed to determine the seroprevalence and the infection rate of MERS-CoV in slaughtered food-camels in Riyadh, Saudi Arabia. A total of 171 nasal swabs along with 161 serum samples were collected during the winter; from January to April 2019. Nasal swabs were examined by Rapid test and RT-qPCR to detect MERS-CoV RNA, while serum samples were tested primarily using S1-based ELISA Kit to detect MERS-CoV (IgG) antibodies and subsequently by MERS pseudotyped viral particles (MERSpp) neutralization assay for confirmation. Genetic diversity of the positive isolates was determined based on the amplification and sequencing of the spike gene. Results: Our results showed high prevalence (38%) of MERS-CoV infection in slaughtered camels and high seropositivity (70.81%) during the time of the study. These data indicate previous and ongoing MERS-CoV infection in camels. Phylogenic analysis revealed relatively low genetic variability among our isolated samples. When these isolates were aligned against published spike sequences of MERS-CoV, deposited in global databases, there was sequence similarity of 94%. Conclusion: High seroprevalence and high genetic stability of MERS-CoV in camels indicating that camels pose a public health threat. The widespread of MERS-CoV infections in camels increases the risk of future zoonotic transmission into people with direct contact with these infected camels. This study confirms re-infections in camels, highlighting a challenge for vaccine development when it comes to protective immunity.

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Pharmacogenomics: The Genomics of Drug Response

Yeast ◽

10.1155/2000/524865 ◽

2000 ◽

Vol 1 (1) ◽

pp. 16-21

Author(s):

Ruth March

Keyword(s):

Genetic Variation ◽

Personalized Medicine ◽

Molecular Basis ◽

Drug Response ◽

Ethical Framework ◽

Disease Genes ◽

Clinical Tests ◽

Huge Amount ◽

The Public ◽

The Right

Pharmacogenomics is defined as the study of the association between genetics and drug response. This is a rapidly expanding field with the hope that, within a few years, prospective genotyping will lead to patients being prescribed drugs which are both safer and more effective (‘the right drug for the right patient’, or personalized medicine). There are many existing examples in the literature of strong associations between genetic variation and drug response, and some of these even form the basis of accepted clinical tests. The molecular basis for some of these associations is described, and includes examples of variation in genes responsible for absorption and metabolism of the drug, and in target and disease genes. However, there are many issues surrounding the legal, regulatory and ethical framework to these studies that remain unanswered, and a huge amount of education both for the public and haelthcare professionals will be needed bafore the results of this new madicine can be widely accepted.

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7. Molecular biology in the clinic

10.1093/actrade/9780198723882.003.0007 ◽

2016 ◽

Author(s):

Aysha Divan ◽

Janice A. Royds

Keyword(s):

Genetic Variation ◽

Molecular Biology ◽

Clinical Research ◽

Clinical Efficacy ◽

Molecular Basis ◽

Disease Risk ◽

Molecular Pathways ◽

Epigenetic Changes ◽

Cellular Processes ◽

Environmental Agents

Environmental agents can cause genetic and epigenetic changes to DNA, the consequences of which lead to deregulation of cellular processes and pathways that cause disease. Genetic variation can either be inherited if acquired through the germline or non-heritable when the DNA changes occur in somatic (body) cells. ‘Molecular biology in the clinic’ discusses two key contemporary areas of clinical research that have benefited from an improved knowledge of their molecular basis: ageing and cancer. It shows that we are now better able to predict disease risk and design drugs that have higher clinical efficacy by targeting specific molecular pathways.

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