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Functional Genomic Approaches (functional + genomic_approach)

Distribution by Scientific Domains

Life Sciences	75%

Selected Abstracts

Functional genomic approach to identify novel genes involved in the regulation of oxidative stress resistance and animal lifespan

AGING CELL, Issue 4 2007
Yongsoon Kim
Summary Genetic studies in many organisms suggest that an increased animal lifespan phenotype is often accompanied by enhanced resistance toward reactive oxygen species (ROS). In Caenorhabditis elegans, mutations in daf-2, which encode an insulin/insulin-like growth factor 1 receptor-like molecule, lead to an extended animal lifespan and increased resistance to ROS. We have optimized an assay to monitor ROS resistance in worms using the ROS-generating chemical paraquat. We have employed this assay to screen the RNAi library along chromosomes III and IV for genes that, when silenced, confer paraquat resistance. The positive RNAi clones were subsequently screened for a lifespan extension phenotype. Using this approach, we have identified 84 genes that, when inactivated by RNAi, lead to significant increases in animal lifespan. Among the 84 genes, 29 were found to act in a manner dependent on daf-16. DAF-16, a forkhead transcription factor, is known to integrate signals from multiple pathways, including the daf-2 pathway, to regulate animal lifespan. Most of the 84 genes have not been previously linked to aging, and potentially participate in important cellular processes such as signal transduction, cell,cell interaction, gene expression, protein degradation, and energy metabolism. Our screen has also identified a group of genes that potentially function in a nutrient-sensing pathway to regulate lifespan in C. elegans. Our study provides a novel approach to identify genes involved in the regulation of aging. [source]

Functional genomics studies on the innate immunity of disease vectors

INSECT SCIENCE, Issue 1 2008
Luke A. Baton
Abstract The increasing availability of genome sequences and the development of high-throughput techniques for gene expression profiling and functional characterization are transforming the study of innate immunity and other areas of insect biology. Already, functional genomic approaches have enabled a quantum advance in the characterization of mosquito immune responses to malaria parasite infection, and similar high-throughput functional genomic studies of other vector-pathogen interactions can be expected in the near future. The application of microarray-based and other expression analyses provide genome-wide transcriptional profiles that can be used to identify insect immune system components that are differentially regulated upon exposure to various classes of pathogens, including many important etiologic agents of human and animal diseases. The role of infection-responsive or other candidate immune genes identified through comparative genomic approaches can then be functionally characterized, either in vivo, for instance in adult mosquitoes, or in vitro using cell lines. In most insect vectors of human pathogens, germ-line transgenesis is still technically difficult and maintenance of multiple transgenic lines logistically demanding. Consequently, transient RNA interference (RNAi)-mediated gene-silencing has rapidly become the method of choice for functional characterization of candidate innate immune genes. The powerful combination of transcriptional profiling in conjunction with assays using RNAi to determine gene function, and identify regulatory pathways, together with downstream cell biological approaches to determine protein localization and interactions, will continue to provide novel insights into the role of insect innate immunity in a variety of vector-pathogen interactions. Here we review advances in functional genomics studies of innate immunity in the insect disease vectors, over the past decade, with a particular focus on the Anopheles mosquito and its responses to malaria infection. [source]

Mechanisms of Regulation of Litter Size in Pigs on the Genome Level

REPRODUCTION IN DOMESTIC ANIMALS, Issue 2007
O Distl
Contents Improvement in litter size has become of great interest in pig industry as good fecundity is directly related to a sow's productive life. Genetic regulation of litter size is complex and the main component traits so far defined are ovulation rate, embryonic survival, uterus capacity, foetal survival and pre-weaning losses. Improvements using concepts of the quantitative genetics let expect only slow genetic progress due to its low heritability of approximately 0.09 for number of piglets born alive. Marker assisted selection allows to dissect litter size in its component traits and using molecular genetic markers for the components of litter size traits promises more progress and advantages in optimum balancing of the different physiological mechanisms influencing litter size. In this review, efforts being made to unravel the genetic determinants of litter size are accounted and discussed. For litter size traits, more than 50 quantitative trait loci (QTL) were mapped and in more than 12 candidate genes associations confirmed. The number of useful candidate genes is much larger as shown by expression profiles and in addition, much more QTL can be assumed. These functional genomic approaches, both QTL mapping and candidate gene analysis, have to be merged for a better understanding of a wider application across different pig breeds and lines. Newly developed tools based on microarray techniques comprising DNA variants or expressed tags of many genes or even the whole genome appear useful for in depth understanding of the genetics of litter size in pigs. [source]

New insights into Chlamydia intracellular survival mechanisms

CELLULAR MICROBIOLOGY, Issue 11 2009
Jordan L. Cocchiaro
Summary Chlamydia sp. are responsible for a wide range of diseases of significant clinical and public health importance. In this review, we highlight how recent cellular and functional genomic approaches have significantly increased our knowledge of the pathogenic mechanisms used by these genetically intractable bacteria. As the extensive repertoire of chlamydial proteins that are translocated into the mammalian host is identified and characterized, a molecular understanding of how Chlamydiae co-opt host cellular functions and block innate immune pathways is beginning to emerge. [source]