Relevant bibliographies by topics / Genetics and genomics/functional genomics

Academic literature on the topic 'Genetics and genomics/functional genomics'

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Published: 10 December 2022
Last updated: 29 January 2023

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Journal articles on the topic "Genetics and genomics/functional genomics"

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Nagy, László G., Zsolt Merényi, Botond Hegedüs, and Balázs Bálint. "Novel phylogenetic methods are needed for understanding gene function in the era of mega-scale genome sequencing." Nucleic Acids Research 48, no. 5 (January 16, 2020): 2209–19. http://dx.doi.org/10.1093/nar/gkz1241.

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Abstract Ongoing large-scale genome sequencing projects are forecasting a data deluge that will almost certainly overwhelm current analytical capabilities of evolutionary genomics. In contrast to population genomics, there are no standardized methods in evolutionary genomics for extracting evolutionary and functional (e.g. gene-trait association) signal from genomic data. Here, we examine how current practices of multi-species comparative genomics perform in this aspect and point out that many genomic datasets are under-utilized due to the lack of powerful methodologies. As a result, many current analyses emphasize gene families for which some functional data is already available, resulting in a growing gap between functionally well-characterized genes/organisms and the universe of unknowns. This leaves unknown genes on the ‘dark side’ of genomes, a problem that will not be mitigated by sequencing more and more genomes, unless we develop tools to infer functional hypotheses for unknown genes in a systematic manner. We provide an inventory of recently developed methods capable of predicting gene-gene and gene-trait associations based on comparative data, then argue that realizing the full potential of whole genome datasets requires the integration of phylogenetic comparative methods into genomics, a rich but underutilized toolbox for looking into the past.
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Bofkin, L., and S. Whelan. "Comparative genomics: Functional needles in a genomic haystack." Heredity 92, no. 5 (April 26, 2004): 363–64. http://dx.doi.org/10.1038/sj.hdy.6800429.

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Penn, Raymond B., Victor E. Ortega, and Eugene R. Bleecker. "A Roadmap to functional genomics." Physiological Genomics 30, no. 1 (June 2007): 82–88. http://dx.doi.org/10.1152/physiolgenomics.00010.2007.

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In August 2006, the Center for Human Genomics of the Wake Forest University School of Medicine in Winston-Salem, NC, hosted the National Institutes of Health-sponsored Roadmap Course entitled Models and Technologies for Defining Phenotype. Twenty-four biomedical and genomic researchers from throughout the world and with varying degrees of experience in the genomics, biological, and biomedical engineering sciences were invited to participate as students in a comprehensive course dedicated to presenting and evaluating current and future approaches that can overcome the problems experienced to date in characterizing the functional consequences of gene variation. A total of 34 senior researchers from four different academic institutions served as course faculty and employed a pedagogical approach that emphasized hands-on workshops, demonstrations, and small group discussions and tasks. Through this report we convey the complex and formidable problems unique to genomics research as we attempt to link the field of genomic research to complex human diseases. Furthermore, we describe the logic and organization of a Roadmap Course designed to teach a diverse group of researchers a multi-disciplinary approach to addressing complex biomedical scenarios in the field of human genomics.
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Soppa, J., A. Baumann, M. Brenneis, M. Dambeck, O. Hering, and C. Lange. "Genomics and functional genomics with haloarchaea." Archives of Microbiology 190, no. 3 (May 21, 2008): 197–215. http://dx.doi.org/10.1007/s00203-008-0376-4.

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Deng, Youping, Hongwei Wang, Ryuji Hamamoto, David Schaffer, and Shiwei Duan. "Functional Genomics, Genetics, and Bioinformatics." BioMed Research International 2015 (2015): 1–3. http://dx.doi.org/10.1155/2015/184824.

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Ludwig, Kerstin U., and Malte Spielmann. "Functional genomics meets human genetics." Medizinische Genetik 34, no. 4 (November 29, 2022): 259–60. http://dx.doi.org/10.1515/medgen-2022-2160.

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Coram, Tristan E., Nitin L. Mantri, Rebecca Ford, and Edwin C. K. Pang. "Functional genomics in chickpea: an emerging frontier for molecular-assisted breeding." Functional Plant Biology 34, no. 10 (2007): 861. http://dx.doi.org/10.1071/fp07169.

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Chickpea is a valuable and important agricultural crop, but yield potential is limited by a series of biotic and abiotic stresses, including Ascochyta blight, Fusarium wilt, drought, cold and salinity. To accelerate molecular breeding efforts for the discovery and introgression of stress tolerance genes into cultivated chickpea, functional genomics approaches are rapidly growing. Recently a series of genetic tools for chickpea have become available that have allowed high-powered functional genomics studies to proceed, including a dense genetic map, large insert genome libraries, expressed sequence tag libraries, microarrays, serial analysis of gene expression, transgenics and reverse genetics. This review summarises the development of these genomic tools and the achievements made in initial and emerging functional genomics studies. Much of the initial research focused on Ascochyta blight resistance, and a resistance model has been synthesised based on the results of various studies. Use of the rich comparative genomics resources from the model legumes Medicago truncatula and Lotus japonicus is also discussed. Finally, perspectives on the future directions for chickpea functional genomics, with the goal of developing elite chickpea cultivars, are discussed.
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Burton, Jeanne L., and Guilherme J. M. Rosa. "Physiological genomics special issue on animal functional genomics." Physiological Genomics 28, no. 1 (December 2006): 1–4. http://dx.doi.org/10.1152/physiolgenomics.00220.2006.

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González-Serna, David, Gonzalo Villanueva-Martin, Marialbert Acosta-Herrera, Ana Márquez, and Javier Martín. "Approaching Shared Pathophysiology in Immune-Mediated Diseases through Functional Genomics." Genes 11, no. 12 (December 9, 2020): 1482. http://dx.doi.org/10.3390/genes11121482.

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Immune-mediated diseases (IMDs) are complex pathologies that are strongly influenced by environmental and genetic factors. Associations between genetic loci and susceptibility to these diseases have been widely studied, and hundreds of risk variants have emerged during the last two decades, with researchers observing a shared genetic pattern among them. Nevertheless, the pathological mechanism behind these associations remains a challenge that has just started to be understood thanks to functional genomic approaches. Transcriptomics, regulatory elements, chromatin interactome, as well as the experimental characterization of genomic findings, constitute key elements in the emerging understandings of how genetics affects the etiopathogenesis of IMDs. In this review, we will focus on the latest advances in the field of functional genomics, centering our attention on systemic rheumatic IMDs.
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Routhier, Etienne, and Julien Mozziconacci. "Genomics enters the deep learning era." PeerJ 10 (June 24, 2022): e13613. http://dx.doi.org/10.7717/peerj.13613.

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The tremendous amount of biological sequence data available, combined with the recent methodological breakthrough in deep learning in domains such as computer vision or natural language processing, is leading today to the transformation of bioinformatics through the emergence of deep genomics, the application of deep learning to genomic sequences. We review here the new applications that the use of deep learning enables in the field, focusing on three aspects: the functional annotation of genomes, the sequence determinants of the genome functions and the possibility to write synthetic genomic sequences.
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Dissertations / Theses on the topic "Genetics and genomics/functional genomics"

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Burnham, Katie. "Functional genomics of the sepsis response." Thesis, University of Oxford, 2017. http://ora.ox.ac.uk/objects/uuid:cb98af40-1b66-4966-a643-ae8dfec2c122.

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Sepsis is defined as a dysregulated immune response to infection causing organ dysfunction, and is a major area of unmet clinical need. Although conventionally considered a unified disease with a common pathway to organ failure and death, substantial clinical and molecular heterogeneity is seen, which has limited efforts to understand pathophysiology and improve therapeutic strategies. Sepsis is associated with global changes in gene expression, and genetic variants are known to affect the response to infection. This thesis therefore uses an integrated functional genomics approach to investigate disease mechanisms and variation in the sepsis response. Data are presented for 551 patients admitted to intensive care with sepsis due to community acquired pneumonia (CAP) or faecal peritonitis (FP). The sepsis response is explored using genome-wide gene expression and proteomics data, and molecular quantitative trait loci (QTL) are mapped in the context of disease. Comparisons with cardiac surgery patients are performed to identify shared and specific aspects of the host response. The host transcriptomic response was largely shared across sources of sepsis, although some specificity relating to viral infection and interferon signalling was observed and validated in prospectively recruited patients. Expression-based sepsis response signature (SRS) subgroups previously described in CAP were validated, and were additionally observed in FP. SRS1 is associated with higher early mortality, and shows enrichment of pathways relating to T cell exhaustion, cell death, and endotoxin tolerance. Differences between SRS groups were also observed in the FP plasma proteome. Serial sampling enabled the investigation of temporal changes in gene expression and protein abundance within patients. Lastly, disease-relevant expression QTL were identified, and interactions with source of sepsis and SRS determined, highlighting the potential impact of regulatory variation on the sepsis response. This thesis demonstrates the benefit of an integrative functional genomics approach to explore heterogeneity in sepsis, and highlights opportunities for patient stratification and personalised medicine.
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Blischak, John David. "Investigating susceptibility to tuberculosis using functional genomics approaches." Thesis, The University of Chicago, 2016. http://pqdtopen.proquest.com/#viewpdf?dispub=10238063.

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A major goal of human genetics is to characterize the role of genetic variation on complex, polygenic phenotypes. With the discovery from genome-wide association studies (GWAS) that many associated variants have a small effect size and are located in non-coding regions of the genome, there has been a large effort to collect functional genomics data. The hope is that a better understanding of how the genome functions in diverse developmental states and environments will provide insight into the context-specific activity of associated non-coding variants. My research applies this paradigm to the complex phenotype of susceptibility to develop tuberculosis (TB). It has been estimated that 10% of individuals infected with Mycobacterium tuberculosis (MTB) progress to active disease. Despite being heritable, very few genetic variants have been associated with susceptibility to TB. For my studies, I use RNA sequencing (RNA-seq) to interrogate genome-wide transcript levels in in vitro cellular models. In Chapter 2, I use a joint Bayesian model to identify genes which are differentially expressed in macrophages only after infection with MTB and related mycobacteria, but not other bacterial pathogens. In Chapter 3, I build a support vector machine model to classify individuals as susceptible or resistant to TB based on the gene expression levels in their dendritic cells. In Chapter 4, I characterize the technical variation introduced by batch processing of single-cell RNA-seq (scRNA-seq) and propose an effective study design that accounts for technical variation while minimizing replication. In addition to providing insight into the genes important for the innate immune response to MTB infection, my work is informative for the design and analysis of future functional genomics experiments. (Note: Supplementary tables are provided in a .zip file available online. Captions for the tables are provided within the dissertation.)

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Moustafa, Ahmed. "Evolutionary and functional genomics of photosynthetic eukaryotes." Diss., University of Iowa, 2009. https://ir.uiowa.edu/etd/311.

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My dissertation focuses on genome and functional evolution of photosynthetic eukaryotes and the design and implementation of computational methods and tools to enable genome-wide studies to investigate these taxa. The work described here is grouped into two major topics, 1) endosymbiosis and genome evolution, and 2) harmful algal blooms. I discuss my work related to endosymbiosis and genome evolution in chapters 2-4. Chapters 5-6 cover the work related to harmful algal blooms. In chapter 1, I introduce the state-of-art of what is known about the history of plastids and evolution of photosynthesis in eukaryotes, an overview of marine harmful algae, and the specific aims of my dissertation. In chapter 2, I describe the design and implementation of the phylogenetic sorting tool, PhyloSort and the assembly of a high-throughput phylogenomic pipeline. Together, PhyloSort and the pipeline has become a key tool for multiple subsequent studies. chapter 2 also presents a case study using these tools in which we provide an estimate of the number of cyanobacterial genes that have been transferred to the nuclear genome of Plantae through primary endosymbiotic gene transfer; I use the model unicellular green alga Chlamydomonas reinhardtii for this purpose. In chapter 3, I discuss another case of prokaryotic contribution to the nucleus of photosynthetic eukaryotes. Here, the intriguing relationship of Chlamydiae-like bacteria and plants and algae is examined in a large-scale analysis, in which we scanned all available genomes of the primary photosynthetic organisms for genes of potential Chlamydiae origin. Surprisingly, we identified more than fifty Chlamydiae-derived genes in plants and algae. Here, we propose a model for the role that a Chlamydiae-like symbiont might have played in the establishment of the primary plastid in the common ancestor of Plantae. In chapter 4, I describe a study in which we explored the complete protein models of two diatom organisms as representative for photosynthetic chromalveolates and looked for genes that might have been acquired through endosymbiotic (secondary) or horizontal transfers from red or green algae. In contradiction of the “chromalveolate hypothesis” which states that photosynthesis in chromalveolates originated via the engulfment of a red alga symbiont, our study shows an unexpected green algal contribution that is fourfold greater than that of the canonical red algal symbiont. Our data suggest that the chromalveolate history includes a previously unrecognized green algal endosymbiont that was captured and lost prior to the more recent establishment of the red alga plastid, which is widespread in extant photosynthetic chromalveolates. In chapter 5, I discuss the identification of the phylogenetic origin of the genes involved in the biosynthetic pathway of saxitoxin in cyanobacteria. Here, we used a pyrosequencing approach to sequence de novo genomes of two strains of Anabaena circinalis, one of which is saxitoxin-producing and the other is non-toxic. Using comparative and phylogenetic analyses, I show that, within the saxitoxin gene cluster, genes that encode the key and unique enzymes in the pathway are of foreign origin that originated via horizontal transfer from non-cyanobacterial sources. These genes introduced the ability to produce saxitoxin in the ancestor of the toxic cyanobacterial clade. In chapter 6, I describe a gene expression study in which we used massively parallel signature sequencing (MPSS) to investigate RNA abundance patterns in the toxic dinoflagellate Alexandrium tamarense. This work provides the first clear evidence for the utilization by dinoflagellates of transcriptional to regulation. Moreover, using MPSS, we provide an estimate of the number of the distinct genes in Alexandrium tamarense; i.e., remarkably 40,000 loci. Taken together, our data indicate that dinoflagellates possess a great metabolic flexibility that allows them to efficiently toggle between photoautotrophy and heterotrophy based on the environmental conditions.
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Mizrachi, Eshchar. "Functional genomics and systems genetics of cellulose biosynthesis in Eucalyptus." Diss., University of Pretoria, 2013. http://hdl.handle.net/2263/79771.

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The globally emerging bioeconomy demands rapid advancement in the sustainable production and utilization of bio-based raw materials for a multitude of downstream applications, particularly in the areas of food, health and bioenergy and biomaterials. These needs, particularly pertaining to plant productivity, quality and stress tolerance, will need to be addressed with advanced biotechnology strategies, which accelerate progress beyond what has been achieved with traditional breeding and cultivation methods. Woody biomass is a readily available source of renewable carbon, and trees from the genus Eucalyptus, displaying superior growth and wood properties and established agricultural practices worldwide, are attractive candidates as short-rotation (5-9 years) feedstocks for biofuels and biomaterials. Guiding advanced strategies in biotechnology in Eucalyptus and other biomass feedstocks requires a sophisticated understanding of the molecular underpinnings of carbon allocation and cell wall biology. In the work presented here, we aimed to characterize the molecular biology of cellulose biosynthesis in Eucalyptus xylem (developing wood) and identify genes, processes and pathways that are linked to and possibly influence this process. We achieved this by detailed characterization of field-grown Eucalyptus hybrid trees, utilizing RNA-sequencing technology and metabolomics of xylem as well as measuring wood properties that are thought to impact the efficiency of industrial processing. Given the lack of information with regards to gene expression in Eucalyptus trees, a major aim was to characterize transcriptomes from various tissues and organs, including a cellulose-enriched form of xylem called tension wood. This involved challenging bioinformatics, which resulted in a high quality assembly and publication of a comprehensive gene catalogue for Eucalyptus, which was one of the first short-read RNA-sequencing based de novo assembly from a eukaryotic organism. We also characterized and modelled the properties of cellulose and xylan biosynthetic pathways as a biological system, the parts of which are segregating in Eucalyptus hybrid tree populations, which has generated novel insights into the allocation and partitioning of sequestered carbon between cellulose, xylan and lignin during active secondary cell wall deposition in woody stem tissues. This research has made important contributions to the field of Eucalyptus biology, but also to the broader field of secondary cell wall biosynthesis in plants, specifically providing (i) resources for transcriptome analysis in a large woody perennial (ii) new biological insight into carbon allocation for polysaccharide biosynthesis in wood, and (iii) annotation and discovery of candidate genes and pathways that may influence wood chemical composition and structures. Importantly, we find that cellulose and xylan biosynthetic genes are transcriptionally hardwired in their co-regulation (along with other important processes for cellulose and xylan transport and deposition), likely due to the fact that they utilize a common source of sucrose-derived carbon for cell wall biosynthesis and the production of sufficient energy to do so. This co-regulation appears to be distinct from the regulation of other cell wall biopolymers. Furthermore, evidence from xylem gene expression and metabolite availability in xylem, as research has made important contributions to the field of Eucalyptus biology, but also to the broader field of secondary cell wall biosynthesis in plants, specifically providing (i) resources for transcriptome analysis in a large woody perennial (ii) new biological insight into carbon allocation for polysaccharide biosynthesis in wood, and (iii) annotation and discovery of candidate genes and pathways that may influence wood chemical composition and structures. Importantly, we find that cellulose and xylan biosynthetic genes are transcriptionally hardwired in their co-regulation (along with other important processes for cellulose and xylan transport and deposition), likely due to the fact that they utilize a common source of sucrose-derived carbon for cell wall biosynthesis and the production of sufficient energy to do so. This co-regulation appears to be distinct from the regulation of other cell wall biopolymers. Furthermore, evidence from xylem gene expression and metabolite availability in xylem, as well as from wood properties of field-grown trees, supports a model in which sucrose-derived cytosolic fructose is shunted to the production of lignin precursors during cellulose and xylan biosynthesis. This model parsimoniously explains a mechanism for trees to partition carbon between polysaccharide and lignin synthesis, and provides exciting new questions and potential strategies to influence carbon allocation in the secondary cell walls of woody plants.
Thesis (PhD)--University of Pretoria, 2013.
Wood and Fibre Molecular Genetics (WFMG) Programme
National Research Foundation (NRF)
Technology and Human Resources for Industry Programme (THRIP)
Genetics
PhD
Unrestricted
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Radhakrishnan, Jayachandran. "Functional genomics of severe sepsis and septic shock." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:2b2afd65-82e0-4847-b7ae-960635b7e884.

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Sepsis is the systemic inflammatory response to an infection. Severe sepsis with multi organ failure is one of the commonest causes of admission to intensive care units, and is associated with poor early and late outcomes. The pathophysiology of sepsis is complex, and poorly understood. This is reflected in the limited and contentious treatment options for sepsis. Genetic factors have been shown to be associated with the risk of and subsequent outcomes from infection. However, clear associations with bacterial sepsis are rare, and even when associations are present their functional effects are often unknown. Gene expression signatures in sepsis are investigated in this project using serial samples obtained from patients admitted to intensive care units with community-acquired pneumonia or faecal peritonitis. The evolving gene expression signatures that define the response to sepsis were identified with large changes seen in genes coding for ribosomal proteins RPS4Y1 and RPS26P54. The differences in the sepsis response between the two diagnostic classes were examined. The gene expression predictors of mortality in sepsis were determined and include genes from the class II MHC HLA-DRB4, HLA-DRB5 and the T cell differentiation protein MAL. The effects of important covariates on gene expression were investigated and their impact on survival related expression determined. The findings were confirmed in a validation cohort. A novel clustering of samples representing distinct inflammatory patterns in a clinically homogeneous population of sepsis patients was identified and related to differences in clinical behaviour. The biological relevance of the differentially expressed genes was ascertained by identifying enriched gene sets. The gene expression changes in sepsis were examined in the context of related clinically relevant immune phenomena: the sterile systemic inflammatory response in patients undergoing elective cardiac surgery and the phenomenon of endotoxin tolerance in PBMCs derived from healthy volunteers. The results highlight the complexities of clinical sepsis and identify hypotheses for future investigations.
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Shao, Diane Donghui. "Functional Genomics Approaches to Identify and Characterize Oncogenic Signaling." Thesis, Harvard University, 2013. http://dissertations.umi.com/gsas.harvard:11076.

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Oncogenes drive cancer by hijacking normal cellular functions involved in proliferation and survival. Suppression of the driving oncogene is highly effective for promoting tumor regression, a phenomenon termed "oncogenic addiction." By using unbiased genetic tools to functionally probe oncogenic addiction, we can identify cancer dependencies and characterize aspects of oncogenic signaling.
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Steinberg, Julia. "Functional genomics analyses of neuropsychiatric and neurodevelopmental disorders." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:e47d1ac2-de92-47d8-864b-dac0bf6669e8.

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Recent large-scale genome-wide studies for many human disorders have identified associations with numerous genetic variants. The biological interpretation of these variants presents a major challenge. In particular, the identification of biological pathways underlying the association could provide crucial insights into the disease aetiologies. In this thesis, I used functional genomics approaches to increase our understanding of neuropsychiatric and neurodevelopmental disorders. Firstly, in an integrative analysis of autism spectrum disorder (ASD), I looked into the role of genes targeted by Fragile-X Mental Retardation Protein ("FMRP targets"). I found evidence that FMRP targets contribute to ASD via two distinct aetiologies: (1) ultra-rare and highly penetrant single disruptions of embryonically upregulated FMRP targets ("single-hit aetiology") or (2) the combination of multiple less penetrant disruptions of synaptic FMRP targets ("multiple-hit aetiology"). In particular, I developed a pathway-association test sensitive to multiple-hit aetiologies. Secondly, I carried out an integrative analysis of bipolar disorder, following up a previously identified association with long-term potentiation. The association was not consistent across independent SNP and CNV datasets. Thirdly, I addressed the difficulty in identifying functional relationships between genes by integrating different datasets into a gene functional-linkage network tuned to the nervous system ("NsNet"). NsNet identified functional links between the genes disrupted by de novo loss-of-function mutations in ASD and, separately, in schizophrenia probands more sensitively than a general functional-linkage network. Fourthly, I considered the challenge of interpreting the phenotypic impact of gene disruptions, focusing on the identification of haploinsufficient genes. I constructed a gene haploinsufficiency score based on genome-wide datasets. Compared to existing approaches, the new score performed better in identifying less-studied haploinsufficient genes. This work both extends the methodology to detect the contribution of genetic variation to neuropsychiatric disorders and also yields insights into the variant genes and the pathways that underlie them. Firstly, in an integrative analysis of autism spectrum disorder (ASD), I looked into the role of genes targeted by Fragile-X Mental Retardation Protein ("FMRP targets"). I found evidence that FMRP targets contribute to ASD via two distinct aetiologies: (1) ultra-rare and highly penetrant single disruptions of embryonically upregulated FMRP targets ("single-hit aetiology") or (2) the combination of multiple less penetrant disruptions of synaptic FMRP targets ("multiple-hit aetiology"). In particular, I developed a pathway-association test sensitive to multiple-hit aetiologies. Secondly, I carried out an integrative analysis of bipolar disorder, following up a previously identified association with long-term potentiation. The association was not consistent across independent SNP and CNV datasets. Thirdly, I addressed the difficulty in identifying functional relationships between genes by integrating different datasets into a gene functional-linkage network tuned to the nervous system ("NsNet"). NsNet identified functional links between the genes disrupted by de novo loss-of-function mutations in ASD and, separately, in schizophrenia probands more sensitively than a general functional-linkage network. Fourthly, I considered the challenge of interpreting the phenotypic impact of gene disruptions, focusing on the identification of haploinsufficient genes. I constructed a gene haploinsufficiency score based on genome-wide datasets. Compared to existing approaches, the new score performed better in identifying less-studied haploinsufficient genes. This work both extends the methodology to detect the contribution of genetic variation to neuropsychiatric disorders and also yields insights into the variant genes and the pathways that underlie them.
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Miller, Michael Ryan. "Functional Genomics of Nervous System Development and Disease." Thesis, University of Oregon, 2011. http://hdl.handle.net/1794/12102.

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xiii, 145 p. : ill. (some col.)
The goal of functional genomics is to elucidate the relationship between an organism's genotype and phenotype. A key characteristic of functional genomics is the use of genome-wide approaches as opposed to more traditional single-gene approaches. Genome-wide expression profiling is used to investigate the dynamic properties of transcriptomes, provides insights into how biological functions are encoded in genomes, and is an important technique in functional genomics. This dissertation describes the use of genome-wide expression profiling and other functional genomics techniques to address a variety of biological questions related to development and disease of the nervous system. Our results reveal novel and important insights into nervous system development and disease and demonstrate the power of functional genomics approaches for the study of nervous system biology. This dissertation also describes a novel technique called TUtagging that facilitates cell type-specific RNA isolation from intact complex tissues. The isolation of RNA from specific cell types within a complex tissue is a major limiting factor in the application of genome-wide expression profiling, and TU-tagging can be used to address a wide array of interesting and important biological questions. This dissertation includes previously published and unpublished co-authored material.
Committee in charge: Dr. John Postlethwait， Chair； Dr. Chris Doe， Advisor； Dr. Bruce Bowerman， Member； Dr. Patrick Phillips， Member； Dr. Tom Stevens， Outside Member
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Butler, Heather. "Functional genomics : analysis of polytene region 38 of Drosophila melanogaster." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0016/MQ55041.pdf.

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Barona, Gómez Francisco. "Functional and structural genomics of amino acid metabolism in Streptomyces coelicolor." Thesis, University of Warwick, 2003. http://wrap.warwick.ac.uk/59424/.

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An investigation of amino acid metabolism in Streptomyces coelicolor, including the anabolism of tryptophan, histidine, the branched-chain amino acids and proline, as well as the catabolism of the latter, is reported. The experiments reported herein were conceptually conceived within a functional genomics framework. For this purpose the complete genome sequence of S. coelicolor was systematically exploited. Moreover, the current knowledge on the physiology of Streptomyces was taken onboard, as well as the prevailing and emerging notions on the evolution of proteins and metabolic pathways. Some of the results obtained using S. coelicolor as a model organism were expanded to other actinomycetes, such as Mycobacterium tuberculosis. This was aided by a comparative genomics analysis of the actinomycetes whose genomes have been sequenced. The theoretical principles that give support to this thesis are introduced in Chapter 1. This study was greatly facilitated by the development of a novel PCRtargeting mutagenesis method of which details can be found in Chapter VII. The discovery of a common isomerase for tryptophan and histidine biosynthesis is reported in Chapter II. This discovery arose from efforts aimed at reconstructing the tryptophan biosynthetic pathway of S. coelicolor, since the genome sequence project of this organism failed to identifiy a trpF gene coding for the enzyme phosphoribosyl anthranilate isomerase. The solution of this functional genomics discrepancy led to the discovery of a putative (~a)8-barrel enzyme, termed PriA, whose preliminary functional and structural characterisation is reported in Chapter III. The evolutionary implications of the discovery of PriA are discussed within Chapters III and N. A comparative genomics analysis of actinomycetes centred on the priA gene is presented in the latter Chapter, supporting the notion that this novel protein is spread across the high (0 + C) content Gram-positive organisms. Indeed, it was predicted that a priA orthologue accounts for the lack of a trpF gene from the genome of M tuberculosis, a hypothesis that proved to be correct. Finally, evidence to support the notion that the histidine and tryptophan biosynthetic pathways co-evolved is presented. In contrast to the isomerisation catalysed by PriA, in which an enzyme is shared by two amino acid biosynthetic pathways, several paralogous enzymes with the potential to account for the first step of tryptophan biosynthesis from chorismate were found on the genome of S. coelicolor. These chorismate-utilising enzymes are investigated in Chapter V. Mutational analysis of some of this paralogues is reported and it is anticipated that the analysis and results reported therein will serve to direct future experiments aimed at identifying the trpE paralogue encoding the enzyme anthranilate synthase. Chapter VI reports on the identification of the proC gene involved in the last step of proline biosynthesis in S. coelicolor. The pyrroline-5-carboxylate reductase activity of the enzyme encoded by the putative proC gene was extensively characterised, with particular emphasis on the interaction between primary and secondary metabolism. Furthermore, mutational analysis of proC suggested that paralogues of this gene are present on the genome of this organism, since its deletion did not lead to an auxotrophic phenotype. Investigation of this observation showed that two paralogous enzymes encoded by i1vC-like genes, involved in biosynthesis of the branched-chain amino acids, are capable of compensating for the lack of proC. This is the first example of a physiological link between the biosynthesis of proline and the branched-chain amino acids. To sum up, the results reported in this thesis represent an advancement towards understanding the physiology of S. coelicolor as a model actinomycete, within a functional and structural genomics framework. They also offer evidence on the evolutionary principles that lead to the appearance of novel proteins and metabolic pathways in bacteria.
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Books on the topic "Genetics and genomics/functional genomics"

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Town, Christopher. Functional genomics. Dordrecht: Springer Science, 2002.

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Erich, Grotewold, ed. Plant functional genomics. Totowa, N.J: Humana Press, 2003.

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Pevsner, Jonathan. Bioinformatics and Functional Genomics. New York: John Wiley & Sons, Ltd., 2005.

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Bioinformatics and functional genomics. Hoboken, NJ: Wiley-Liss, 2004.

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Marsupial genetics and genomics. Dordrecht: Springer, 2010.

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Bioinformatics and functional genomics. 2nd ed. Hoboken, N.J: Wiley, 2009.

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1951-, Stacey Gary, ed. Genetics and genomics of soybean. New York: Springer, 2008.

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Burnap, Robert. Functional Genomics and Evolution of Photosynthetic Systems. Dordrecht: Springer Science +Business Media B.V., 2012.

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Phenotypic variation: Exploration and functional genomics. Oxford: Oxford University Press, 2010.

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The handbook of plant functional genomics: Concepts and protocols. Weinheim: Wiley-Blackwell, 2008.

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Book chapters on the topic "Genetics and genomics/functional genomics"

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Mondal, Tapan Kumar. "Functional Genomics." In Tea: Genome and Genetics, 229–308. Singapore: Springer Singapore, 2020. http://dx.doi.org/10.1007/978-981-15-8868-6_8.

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Allan, Andrew C., Ross Crowhurst, Andrew Gleave, Richard Newcomb, and Robert Schaffer. "Apple Functional Genomics." In Genetics and Genomics of Rosaceae, 121–42. New York, NY: Springer New York, 2009. http://dx.doi.org/10.1007/978-0-387-77491-6_6.

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Nowrousian, M., J. C. Dunlap, and M. A. Nelson. "Functional Genomics in Fungi." In Genetics and Biotechnology, 115–28. Berlin, Heidelberg: Springer Berlin Heidelberg, 2004. http://dx.doi.org/10.1007/978-3-662-07426-8_7.

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Blaby, Ian K., and Crysten E. Blaby-Haas. "Genomics and Functional Genomics in Chlamydomonas reinhardtii." In Chlamydomonas: Molecular Genetics and Physiology, 1–26. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-66365-4_1.

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Abbott, Albert G., Bryon Sosinski, and Ariel Orellana. "Functional Genomics in Peach." In Genetics and Genomics of Rosaceae, 259–75. New York, NY: Springer New York, 2009. http://dx.doi.org/10.1007/978-0-387-77491-6_12.

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Foucher, Fabrice. "Functional Genomics in Rose." In Genetics and Genomics of Rosaceae, 381–92. New York, NY: Springer New York, 2009. http://dx.doi.org/10.1007/978-0-387-77491-6_18.

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Zhang, Jisen, Marvellous Zhou, James Walsh, Lin Zhu, Youqiang Chen, and Ray Ming. "Sugarcane Genetics and Genomics." In Sugarcane: Physiology, Biochemistry, and Functional Biology, 623–43. Chichester, UK: John Wiley & Sons Ltd, 2013. http://dx.doi.org/10.1002/9781118771280.ch23.

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Larkin, M. J., L. A. Kulakov, and C. C. R. Allen. "Rhodococcus: Genetics and Functional Genomics." In Handbook of Hydrocarbon and Lipid Microbiology, 1345–53. Berlin, Heidelberg: Springer Berlin Heidelberg, 2010. http://dx.doi.org/10.1007/978-3-540-77587-4_94.

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Coulouarn, Cédric, and Snorri S. Thorgeirsson. "Integrative and Functional Genomics of HCC." In Molecular Genetics of Liver Neoplasia, 221–40. New York, NY: Springer New York, 2010. http://dx.doi.org/10.1007/978-1-4419-6082-5_12.

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Walker, Scott S., Chad Houseweart, and Teresa J. Kenney. "Genetic Footprinting for Bacterial Functional Genomics." In Prokaryotic Genomics, 90–101. Basel: Birkhäuser Basel, 2003. http://dx.doi.org/10.1007/978-3-0348-8963-6_8.

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Conference papers on the topic "Genetics and genomics/functional genomics"

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"Plant cell wall as a target for functional genomics." In Plant Genetics, Genomics, Bioinformatics, and Biotechnology. Novosibirsk ICG SB RAS 2021, 2021. http://dx.doi.org/10.18699/plantgen2021-068.

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"Functional characteristics of EST-SSR markers in Pinus sylvestris L." In Plant Genetics, Genomics, Bioinformatics, and Biotechnology. Novosibirsk ICG SB RAS 2021, 2021. http://dx.doi.org/10.18699/plantgen2021-075.

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"Functional analysis of Solanum lycopersicum L. MADS-box gene SlMADS5." In Plant Genetics, Genomics, Bioinformatics, and Biotechnology. Novosibirsk ICG SB RAS 2021, 2021. http://dx.doi.org/10.18699/plantgen2021-140.

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"Functional characterization of papain-like cysteine proteases genes in rice." In Plant Genetics, Genomics, Bioinformatics, and Biotechnology. Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 2019. http://dx.doi.org/10.18699/plantgen2019-124.

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"Functional characterization of genes with circadian expression patterns in common wheat." In Plant Genetics, Genomics, Bioinformatics, and Biotechnology. Novosibirsk ICG SB RAS 2021, 2021. http://dx.doi.org/10.18699/plantgen2021-098.

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"Structural and functional characterization of transcription factor binding sites: from bioinformatics to hormone biosensors." In Plant Genetics, Genomics, Bioinformatics, and Biotechnology. Novosibirsk ICG SB RAS 2021, 2021. http://dx.doi.org/10.18699/plantgen2021-038.

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"Bioresource collections of vegetable plants as an initial material for breeding cultivars with high biochemical value and for obtaining functional foods." In Plant Genetics, Genomics, Bioinformatics, and Biotechnology. Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 2019. http://dx.doi.org/10.18699/plantgen2019-056.

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"Polyphenol oxidase gene family in barley (Hordeum vulgare L.): structural organization and functional activity of the genes in respect to black grain pigment formation." In Plant Genetics, Genomics, Bioinformatics, and Biotechnology. Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 2019. http://dx.doi.org/10.18699/plantgen2019-104.

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"Functional characterization of Stagonospora nodorum necrotrophic effectors." In Current Challenges in Plant Genetics, Genomics, Bioinformatics, and Biotechnology. Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences Novosibirsk State University, 2019. http://dx.doi.org/10.18699/icg-plantgen2019-21.

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"The protective functions of progesterone system of hormonal regulation in higher plants." In Plant Genetics, Genomics, Bioinformatics, and Biotechnology. Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 2019. http://dx.doi.org/10.18699/plantgen2019-171.

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Reports on the topic "Genetics and genomics/functional genomics"

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Mawassi, Munir, Baozhong Meng, and Lorne Stobbs. Development of Virus Induced Gene Silencing Tools for Functional Genomics in Grapevine. United States Department of Agriculture, July 2013. http://dx.doi.org/10.32747/2013.7613887.bard.

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Grapevine is perhaps the most widely grown fruit crop. To understand the genetic make-up so as to improve the yield and quality of grapes and grape products, researchers in Europe have recently sequenced the genomes of Pinot noir and its inbred. As expected, function of many grape genes is unknown. Functional genomics studies have become the major focus of grape researchers and breeders. Current genetic approaches for gene function studies include mutagenesis, crossing and genetic transformation. However, these approaches are difficult to apply to grapes and takes long periods of time to accomplish. It is thus imperative to seek new ways for grape functional genomics studies. Virus-induced gene silencing (VIGS) offers an attractive alternative for this purpose and has proven highly effective in several herbaceous plant species including tomato, tobacco and barley. VIGS offers several advantages over existing functional genomics approaches. First, it does not require transformation to silence a plant gene target. Instead, it induces silencing of a plant gene through infection with a virus that contains the target gene sequence, which can be accomplished within a few weeks. Second, different plant genes can be readily inserted into the viral genome via molecular cloning and functions of a large number of genes can be identified within a short period of time. Our long-term goal of this research is to develop VIGS-based tools for grapevine functional genomics, made of the genomes of Grapevine virus A (GVA) from Israel and Grapevine rupestris stem pitting-associated virus (GRSPaV) from Canada. GVA and GRSPaV are members of the Flexiviridae. Both viruses have single-stranded, positive sense RNA genomes, which makes them easy to manipulate genetically and excellent candidates as VIGS vectors. In our three years research, several major breakthroughs have been made by the research groups involved in this project. We have engineered a cDNA clone of GVA into a binary vector that is infectious upon delivery into plantlets of micropropagated Vitis viniferacv. Prime. We further developed the GVA into an expression vector that successfully capable to silence endogenous genes. We also were able to assemble an infectious full-length cDNA clones of GRSPaV. In the following sections Achievements and Detailed description of the research activities, we are presenting the outcome and results of this research in details.
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Ron, Eliora, and Eugene Eugene Nester. Global functional genomics of plant cell transformation by agrobacterium. United States Department of Agriculture, March 2009. http://dx.doi.org/10.32747/2009.7695860.bard.

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The aim of this study was to carry out a global functional genomics analysis of plant cell transformation by Agrobacterium in order to define and characterize the physiology of Agrobacterium in the acidic environment of a wounded plant. We planed to study the proteome and transcriptome of Agrobacterium in response to a change in pH, from 7.2 to 5.5 and identify genes and circuits directly involved in this change. Bacteria-plant interactions involve a large number of global regulatory systems, which are essential for protection against new stressful conditions. The interaction of bacteria with their hosts has been previously studied by genetic-physiological methods. We wanted to make use of the new capabilities to study these interactions on a global scale, using transcription analysis (transcriptomics, microarrays) and proteomics (2D gel electrophoresis and mass spectrometry). The results provided extensive data on the functional genomics under conditions that partially mimic plant infection and – in addition - revealed some surprising and significant data. Thus, we identified the genes whose expression is modulated when Agrobacterium is grown under the acidic conditions found in the rhizosphere (pH 5.5), an essential environmental factor in Agrobacterium – plant interactions essential for induction of the virulence program by plant signal molecules. Among the 45 genes whose expression was significantly elevated, of special interest is the two-component chromosomally encoded system, ChvG/I which is involved in regulating acid inducible genes. A second exciting system under acid and ChvG/Icontrol is a secretion system for proteins, T6SS, encoded by 14 genes which appears to be important for Rhizobium leguminosarum nodule formation and nitrogen fixation and for virulence of Agrobacterium. The proteome analysis revealed that gamma aminobutyric acid (GABA), a metabolite secreted by wounded plants, induces the synthesis of an Agrobacterium lactonase which degrades the quorum sensing signal, N-acyl homoserine lactone (AHL), resulting in attenuation of virulence. In addition, through a transcriptomic analysis of Agrobacterium growing at the pH of the rhizosphere (pH=5.5), we demonstrated that salicylic acid (SA) a well-studied plant signal molecule important in plant defense, attenuates Agrobacterium virulence in two distinct ways - by down regulating the synthesis of the virulence (vir) genes required for the processing and transfer of the T-DNA and by inducing the same lactonase, which in turn degrades the AHL. Thus, GABA and SA with different molecular structures, induce the expression of these same genes. The identification of genes whose expression is modulated by conditions that mimic plant infection, as well as the identification of regulatory molecules that help control the early stages of infection, advance our understanding of this complex bacterial-plant interaction and has immediate potential applications to modify it. We expect that the data generated by our research will be used to develop novel strategies for the control of crown gall disease. Moreover, these results will also provide the basis for future biotechnological approaches that will use genetic manipulations to improve bacterial-plant interactions, leading to more efficient DNA transfer to recalcitrant plants and robust symbiosis. These advances will, in turn, contribute to plant protection by introducing genes for resistance against other bacteria, pests and environmental stress.
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Sessa, Guido, and Gregory Martin. A functional genomics approach to dissect resistance of tomato to bacterial spot disease. United States Department of Agriculture, January 2004. http://dx.doi.org/10.32747/2004.7695876.bard.

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The research problem. Bacterial spot disease in tomato is of great economic importance worldwide and it is particularly severe in warm and moist areas affecting yield and quality of tomato fruits. Causal agent of spot disease is the Gram-negative bacterium Xanthomonas campestris pv. vesicatoria (Xcv), which can be a contaminant on tomato seeds, or survive in plant debris and in association with certain weeds. Despite the economic significance of spot disease, plant protection against Xcvby cultural practices and chemical control have so far proven unsuccessful. In addition, breeding for resistance to bacterial spot in tomato has been undermined by the genetic complexity of the available sources of resistance and by the multiple races of the pathogen. Genetic resistance to specific Xcvraces have been identified in tomato lines that develop a hypersensitive response and additional defense responses upon bacterial challenge. Central goals of this research were: 1. To identify plant genes involved in signaling and defense responses that result in the onset of resistance. 2. To characterize molecular properties and mode of action of bacterial proteins, which function as avirulence or virulence factors during the interaction between Xcvand resistant or susceptible tomato plants, respectively. Our main achievements during this research program are in three major areas: 1. Identification of differentially expressed genes during the resistance response of tomato to Xcvrace T3. A combination of suppression subtractive hybridization and microarray analysis identified a large set of tomato genes that are induced or repressed during the response of resistant plants to avirulent XcvT3 bacteria. These genes were grouped in clusters based on coordinate expression kinetics, and classified into over 20 functional classes. Among them we identified genes that are directly modulated by expression of the type III effector protein AvrXv3 and genes that are induced also during the tomato resistance response to Pseudomonas syringae pv. tomato. 2. Characterization of molecular and biochemical properties of the tomato LeMPK3MAP kinase. A detailed molecular and biochemical analysis was performed for LeMPK3 MAP kinase, which was among the genes induced by XcvT3 in resistant tomato plants. LeMPK3 was induced at the mRNA level by different pathogens, elicitors, and wounding, but not by defense-related plant hormones. Moreover, an induction of LeMPK3 kinase activity was observed in resistant tomato plants upon Xcvinfection. LeMPK3 was biochemically defined as a dual-specificity MAP kinase, and extensively characterized in vitro in terms of kinase activity, sites and mechanism of autophosphorylation, divalent cation preference, Kₘand Vₘₐₓ values for ATP. 3. Characteriztion of molecular properties of the Xcveffector protein AvrRxv. The avirulence gene avrRxvis involved in the genetic interaction that determines tomato resistance to Xcvrace T1. We found that AvrRxv functions inside the plant cell, localizes to the cytoplasm, and is sufficient to confer avirulence to virulent Xcvstrains. In addition, we showed that the AvrRxv cysteine protease catalytic core is essential for host recognition. Finally, insights into cellular processes activated by AvrRxv expression in resistant plants were obtained by microarray analysis of 8,600 tomato genes. Scientific and agricultural significance: The findings of these activities depict a comprehensive and detailed picture of cellular processes taking place during the onset of tomato resistance to Xcv. In this research, a large pool of genes, which may be involved in the control and execution of plant defense responses, was identified and the stage is set for the dissection of signaling pathways specifically triggered by Xcv.
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Avni, Adi, and Kirankumar S. Mysore. Functional Genomics Approach to Identify Signaling Components Involved in Defense Responses Induced by the Ethylene Inducing Xyalanase Elicitor. United States Department of Agriculture, December 2009. http://dx.doi.org/10.32747/2009.7697100.bard.

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Plant-microbe interactions involve a large number of global regulatory systems, which are essential for plants to protect themselves against pathogen attack. An ethylene-inducing xylanase (EIX) of Trichoderma viride is a potent elicitor of plant defense responses, like hypersensitive response (HR), in specific cultivars of tobacco (Nicotiana tabacum) and tomato (Lycopersicon esculentum). The central goal of this proposal was to investigate the molecular mechanisms that allow plants to specifically activate defense responses after EIX treatment. We proposed to identify cellular signaling components involved in the induction of HR by the EIX elicitor. The molecular genetic analysis of the signal transduction pathway that modulates hypersensitive responses is an important step in understanding the induction of plant defense responses. The genes that mediate LeEIX2-EIX dependent activation of resistance mechanisms remain to be identified. We used two approaches to identify the cellular signaling components that induce HR mediated by the EIX elicitor. In the first approach, we performed a yeast two-hybrid screening using LeEix2 as bait to identify plant proteins that interact with it. In the second approach, we used virus-induced gene silencing (VIGS) for a high-throughput screen to identify genes that are required for the induction of LeEIX2-EIX mediated HR. VIGS will also be used for functional characterization of genes that will be identified during the yeast two-hybrid screen. This investigation will shed light on cellular processes and signaling components involved in induction of general plant defense against pathogens and will provide the basis for future biotechnological approaches to improve plant resistance to pathogens. Several genes were indentified by the two approaches. We used the VIGS and yeast two hybrid approaches to confirm that activity of the genes initially identified by different procedure. Two genes inhibit the induction of HR by the fungal elicitor in the different systems; Tobacco-Harpin binding protein 1 and cyclopropyl isomerase.
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Abbott, Albert G., Doron Holland, Douglas Bielenberg, and Gregory Reighard. Structural and Functional Genomic Approaches for Marking and Identifying Genes that Control Chilling Requirement in Apricot and Peach Trees. United States Department of Agriculture, September 2009. http://dx.doi.org/10.32747/2009.7591742.bard.

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Structural and functional genomic approaches for marking and identifying genes that control chilling requirement in apricot and peach trees. Specific aims: 1) Identify and characterize the genetic nature of chilling requirement for flowering and dormancy break of vegetative shoots in Prunusgermplasm through the utilization of existing apricot (NeweYa'ar Research Center, ARO) and peach (Clemson University) genetic mapping populations; 2) Use molecular genetic mapping techniques to identify markers flanking genomic regions controlling chilling; 3) Comparatively map the regions controlling chilling requirement in apricot and peach and locate important genomic regions influencing chilling requirement on the Prunus functional genomic database as an initial step for identification of candidate genes; 4) Develop from the functional genomics database a set of markers facilitating the development of cultivars with optimized chilling requirements for improved and sustained fruit production in warm-winter environments. Dormant apricot (prunus armeniaca L.) and peach [Prunus persica (L.) Batsch] trees require sustained exposure to low, near freezing, temperatures before vigorous floral and vegetative bud break is possible after the resumption of warm temperatures in the spring. The duration of chilling required (the chilling requirement, CR) is determined by the climatic adaptation of the particular cultivar, thus limiting its geographic distribution. This limitation is particularly evident when attempting to introduce superior cultivars to regions with very warm winter temperatures, such as Israel and the coastal southern United States. The physiological mechanism of CR is not understood and although breeding programs deliberately manipulate CR in apricot and peach crosses, robust closely associated markers to the trait are currently not available. We used segregating populations of apricot (100 Fl individuals, NeweYa'ar Research Center, ARO) and peach (378 F2 individuals, Clemson University) to discover several discreet genomic loci that regulate CR and blooming date. We used the extensive genomic/genetic resources available for Prunus to successfully combine our apricot and peach genetic data and identify five QTL with strong effects that are conserved between species as well as several QTL that are unique to each species. We have identified markers in the key major QTL regions for testing in breeding programs which we are carrying out currently; we have identified an initial set of candidate genes using the peach physical/transcriptome map and whole peach genome sequences and we are testing these currently to identify key target genes for manipulation in breeding programs. Our collaborative work to date has demonstrated the following: 1) CR in peach and apricot is predominantly controlled by a limited number ofQTL loci, seven detected in a peach F2 derived map comprising 65% of the character and 12 in an apricot Fl map comprising 71.6% and 55.6% of the trait in the Perfection and A. 1740 parental maps, respectively and that peach and apricot appear in our initial maps to share five genomic intervals containing potentially common QTL. 2) Application of common anchor markers of the Prunus/peach, physical/genetic map resources has allowed us not only to identify the shared intervals but also to have immediately available some putative candidate gene information from these intervals, the EVG region on LG1 in peach the TALY 1 region in apricot on LG2 in peach; and several others involved in vernalization pathways (LGI and LG7). 3) Mapped BACcontigs are easily defined from the complete physical map resources in peach through the common SSR markers that anchor our CR maps in the two species, 4) Sequences of BACs in these regions can be easily mined for additional polymorphic markers to use in MAS applications.
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Mawassi, Munir, and Valerian V. Dolja. Role of the viral AlkB homologs in RNA repair. United States Department of Agriculture, June 2014. http://dx.doi.org/10.32747/2014.7594396.bard.

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AlkB proteins that repair DNA via reversing methylation damage are conserved in a broad range of prokaryotes and eukaryotes including plants. Surprisingly, AlkB-domains were discovered in the genomes of numerous plant positive-strand RNA viruses, majority of which belong to the family Flexiviridae. The major goal of this research was to reveal the AlkB functions in the viral infection cycle using a range of complementary genetic and biochemical approaches. Our hypotheses was that AlkB is required for efficient replication and genetic stability of viral RNA genomes The major objectives of the research were to identify the functions of GVA AlkB domain throughout the virus infection cycle in N. benthamiana and grapevine, to investigate possible RNA silencing suppression activity of the viral AlkBs, and to characterize the RNA demethylation activity of the mutated GVA AlkBs in vitro and in vivo to determine methylation status of the viral RNA. Over the duration of project, we have made a very substantial progress with the first two objectives. Because of the extreme low titer of the virus particles in plants infected with the AlkB mutant viruses, we were unable to analyze RNA demethylation activity and therefore had to abandon third objective. The major achievements with our objectives were demonstration of the AlkB function in virus spread and accumulation in both experimental and natural hosts of GVA, discovery of the functional cooperation and physical interaction between AlkB and p10 AlkB in suppression of plant RNA silencing response, developing a powerful virus vector technology for grapevine using GLRaV-2-derived vectors for functional genomics and pathogen control in grapevine, and in addition we used massive parallel sequencing of siRNAs to conduct comparative analysis of the siRNA populations in grape plants infected with AlkB-containing GLRaV-3 versus GLRaV-2 that does not encode AlkB. This analysis revealed dramatically reduced levels of virus-specific siRNAs in plants infected with GLRaV-3 compared to that in GLRaV-2 infection implicating AlkB in suppression of siRNA formation. We are pleased to report that BARD funding resulted in 5 publications directly supported by BARD, one US patent, and 9 more publications also relevant to project. Moreover, two joint manuscripts that summarize work on GVA AlkB (led by Israeli PI) and on viral siRNAs in grapevine (led by US PI in collaboration with University of Basel) are in preparation.
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Klein, Eric, and Yaw Nyame. The genetics and genomics of prostate cancer. BJUI Knowledge, July 2019. http://dx.doi.org/10.18591/bjuik.0152.

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Lennie, Peter. Facilities and Equipment for Genomics/Comparative Functional Genomics at New York University. Office of Scientific and Technical Information (OSTI), June 2006. http://dx.doi.org/10.2172/898062.

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Yuen, Gary, Serge Edme, Gautam Sarath, Nathan Palmer, Satyanarayana Tatineni, and Robert Mitchell. Genetics and Genomics of Pathogen Resistance in Switchgrass. Office of Scientific and Technical Information (OSTI), December 2020. http://dx.doi.org/10.2172/1783170.

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Lers, Amnon, and Gan Susheng. Study of the regulatory mechanism involved in dark-induced Postharvest leaf senescence. United States Department of Agriculture, January 2009. http://dx.doi.org/10.32747/2009.7591734.bard.

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Postharvest leaf senescence contributes to quality losses in flowers and leafy vegetables. The general goal of this research project was to investigate the regulatory mechanisms involved in dark-induced leaf senescence. The regulatory system involved in senescence induction and control is highly complex and possibly involves a network of senescence promoting pathways responsible for activation of the senescence-associated genes. Pathways involving different internal signals and environmental factors may have distinctive importance in different leaf senescence systems. Darkness is known to have a role in enhancement of postharvest leaf senescence and for getting an insight into its regulatory mechanism/s we have applied molecular genetics and functional genomics approaches. The original objectives were: 1. Identification of dark-induced SAGs in Arabidopsis using enhancer/promoter trap lines and microarray approaches; 2. Molecular and functional characterization of the identified genes by analyzing their expression and examining the phenotypes in related knockout mutant plants; 3. Initial studies of promoter sequences for selected early dark-induced SAGs. Since genomic studies of senescence, with emphasis on dark-induced senescence, were early-on published which included information on potential regulatory genes we decided to use this new information. This is instead of using the uncharacterized enhancer/promoter trap lines as originally planned. We have also focused on specific relevant genes identified in the two laboratories. Based on the available genomic analyses of leaf senescence 10 candidate genes hypothesized to have a regulatory role in dark-induced senescence were subjected to both expression as well as functional analyses. For most of these genes senescence-specific regulation was confirmed, however, functional analyses using knock-out mutants indicated no consequence to senescence progression. The transcription factor WARK75 was found to be specifically expressed during natural and dark-induced leaf senescence. Functional analysis demonstrated that in detached leaves senescence under darkness was significantly delayed while no phenotypic consequences could be observed on growth and development, including no effect on natural leaf senescence,. Thus, WARKY75 is suggested to have a role in dark-induced senescence, but not in natural senescence. Another regulatory gene identified to have a role in senescence is MKK9 encoding for a Mitogen-Activated Protein Kinase Kinase 9 which is upregulated during senescence in harvested leaves as well as in naturally senescing leaves. MKK9 can specifically phosphorylate another kinase, MPK6. Both knockouts of MKK9 and MPK6 displayed a significantly senescence delay in harvested leaves and possibly function as a phosphorelay that regulates senescence. To our knowledge, this is the first report that clearly demonstrates the involvement of a MAP kinase pathway in senescence. This research not only revealed a new signal transduction pathway, but more important provided significant insights into the regulatory mechanisms underlying senescence in harvested leaves. In an additional line of research we have employed the promoter of the senescence-induced BFN1 gene as a handle for identifying components of the regulatory mechanism. This gene was shown to be activated during darkinduced senescence of detached leaves, as well as natural senescence. This was shown by following protein accumulation and promoter activity which demonstrated that this promoter is activated during dark-induced senescence. Analysis of the promoter established that, at least some of the regulatory sequences reside in an 80 bps long fragment of the promoter. Overall, progress was made in identification of components with a role in dark-induced senescence in this project. Further studies should be done in order to better understand the function of these components and develop approaches for modulating the progress of senescence in crop plants for the benefit of agriculture.
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