13 research outputs found

    The Indian cobra reference genome and transcriptome enables comprehensive identification of venom toxins

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    Snakebite envenoming is a serious and neglected tropical disease that kills ~100,000 people annually. High-quality, genome-enabled comprehensive characterization of toxin genes will facilitate development of effective humanized recombinant antivenom. We report a de novo near-chromosomal genome assembly of Naja naja, the Indian cobra, a highly venomous, medically important snake. Our assembly has a scaffold N50 of 223.35 Mb, with 19 scaffolds containing 95% of the genome. Of the 23,248 predicted protein-coding genes, 12,346 venom-gland-expressed genes constitute the \u27venom-ome\u27 and this included 139 genes from 33 toxin families. Among the 139 toxin genes were 19 \u27venom-ome-specific toxins\u27 (VSTs) that showed venom-gland-specific expression, and these probably encode the minimal core venom effector proteins. Synthetic venom reconstituted through recombinant VST expression will aid in the rapid development of safe and effective synthetic antivenom. Additionally, our genome could serve as a reference for snake genomes, support evolutionary studies and enable venom-driven drug discovery

    SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

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    Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

    A first update on mapping the human genetic architecture of COVID-19

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    Identification of dopamine receptors across the extant avian family tree and analysis with other clades uncovers a polyploid expansion among vertebrates.

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    Dopamine is an important central nervous system transmitter that functions through two classes of receptors (D1 and D2) to influence a diverse range of biological processes in vertebrates. With roles in regulating neural activity, behavior, and gene expression, there has been great interest in understanding the function and evolution dopamine and its receptors. In this study, we use a combination of sequence analyses, microsynteny analyses, and phylogenetic relationships to identify and characterize both the D1 (DRD1A, DRD1B, DRD1C, and DRD1E) and D2 (DRD2, DRD3, and DRD4) dopamine receptor gene families in 43 recently sequenced bird genomes representing the major ordinal lineages across the avian family tree. We show that the common ancestor of all birds possessed at least seven D1 and D2 receptors, followed by subsequent independent losses in some lineages of modern birds. Through comparisons with other vertebrate and invertebrate species we show that two of the D1 receptors, DRD1A and DRD1B, and two of the D2 receptors, DRD2 and DRD3, originated from a whole genome duplication event early in the vertebrate lineage, providing the first conclusive evidence of the origin of these highly conserved receptors. Our findings provide insight into the evolutionary development of an important modulatory component of the central nervous system in vertebrates, and will help further unravel the complex evolutionary and functional relationships among dopamine receptors

    Evolinc: A Tool for the Identification and Evolutionary Comparison of Long Intergenic Non-coding RNAs

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    Long intergenic non-coding RNAs (lincRNAs) are an abundant and functionally diverse class of eukaryotic transcripts. Reported lincRNA repertoires in mammals vary, but are commonly in the thousands to tens of thousands of transcripts, covering similar to 90% of the genome. In addition to elucidating function, there is particular interest in understanding the origin and evolution of lincRNAs. Aside from mammals, lincRNA populations have been sparsely sampled, precluding evolutionary analyses focused on their emergence and persistence. Here we present Evolinc, a two-module pipeline designed to facilitate lincRNA discovery and characterize aspects of lincRNA evolution. The first module (Evolinc-I) is a lincRNA identification workflow that also facilitates downstream differential expression analysis and genome browser visualization of identified lincRNAs. The second module (Evolinc-II) is a genomic and transcriptomic comparative analysis workflow that determines the phylogenetic depth to which a lincRNA locus is conserved within a user-defined group of related species. Here we validate lincRNA catalogs generated with Evolinc-I against previously annotated Arabidopsis and human lincRNA data. Evolinc-I recapitulated earlier findings and uncovered an additional 70 Arabidopsis and 43 human lincRNAs. We demonstrate the usefulness of Evolinc-II by examining the evolutionary histories of a public dataset of 5,361 Arabidopsis lincRNAs. We used Evolinc-II to winnow this dataset to 40 lincRNAs conserved across species in Brassicaceae. Finally, we show how Evolinc-II can be used to recover the evolutionary history of a known lincRNA, the human telomerase RNA (TERC). These latter analyses revealed unexpected duplication events as well as the loss and subsequent acquisition of a novel TERC locus in the lineage leading to mice and rats. The Evolinc pipeline is currently integrated in CyVerse's Discovery Environment and is free for use by researchers.National Science Foundation [IOS-1444490]; NSF-MCB [1409251]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

    Genomic-based breeding for climate-smart peach varieties

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    Improving the performance of peach varieties in the context of climate change requires multiple approaches. Not only will climate change alter plant phenology, but it will also drive negative effects of several biotic and abiotic stressors. The challenge is to improve adaptation of varieties to a changing environment, while maintaining organoleptic qualities of the fruit. This chapter focuses on the progress in genomics-assisted breeding in peach to break barriers in conventional breeding. Breeding climate-smart (CS) peach trees requires the identification of CS traits used in the adaptation to high levels of temperature, CO2, water deprivation and biotic stress. Relevant CS traits, such as those that control flowering time (chilling and heat requirements), biotic and abiotic stress tolerance (pests and diseases; water-nutrient efficiency), require prioritization. Here, we review classical mapping and breeding of peach varieties, the progress and limitations of the used of marker-assisted selection and breeding (MAS and MAB, respectively) in expression of traits, such as fruit quality and stress tolerance, and describe the rationale for the use of molecular breeding.EEA San PedroFil: Gogorcena Aoiz, Yolanda. Consejo Superior de Investigaciones Científicas (CSIC). Estación Experimental Aula Dei; EspañaFil: Sánchez, Gerardo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria San Pedro; ArgentinaFil: Moreno-Vázquez Santiago. Universidad Politécnica de Madrid. Escuela Técnica Superior de Ingeniería Agronómica, Alimentaria y de Biosistemas; EspañaFil: Pérez, Salvador. Centro de Recursos Geneticos y Mejoramiento de Prunus; MéxicoFil: Ksouri, Najla. Consejo Superior de Investigaciones Científicas (CSIC). Estación Experimental Aula Dei; Españ
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