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Anouncements • • • • Lab tonight: 1245 SC Bring own laptop/computer is welcome CSS accounts Questions about Perl install (which is perfect for Lab) • Lectures have been mapped out further on web • Next paper (probably tonight). 1 Review Central Dogma • Transcription • Translation 2 Summary of Paper • Where are we in Genomics? • J.F. Hocquette • Journal of Physiology and Pharmacology, 2005, 56, Supp 3, 37-70 • Herbivore Research Unit • Saint-Genes Champanelle, France 3 Genomics • Classically divided into two basic areas – structural genomics -- characterization of the physical nature of whole genomes – functional genomics -- the characterization of overall patterns of genes expression • Two "new paradigms" – view is more global due to the development of high-throughput techniques – development of bioinformatics -- (needs the use of computers to manage biological information) -direct consequence of more information available derived from genomics studies. 4 Genomes • 240 genomes sequenced • 1000 in progress (with links in paper) • What are all of the genes -- not completely solved (ex. yeast ORFs still being corrected) • ENCyclopedia Of DNA Elements (ENCODE) -develop techniques to identify all protein-coding genes, non-protein coding genes, and any other DNA elements • www.genome.gov/ENCODE • "Most of our genome is 'silent' • "It was also observed in humans that introns are, on average, 14 times shorter in highly expressed 5 than in low expressed genes." Why? Misc. • "It was recently demonstrated that the spatial organization of chromosomes is tissuespecific." • polymorphism -- DNA sequence differences between organisms, species, or individuals (of same species) • pharmacogenetics -- inherited differences in DNA which affects drug metabolism) • nutrigenetics -- inherited differences in DNA which affects diet response • pharmacogenomics -- study of the genes that 6 determin drug behavior and response Misc • SNPs: www.ncbi.nlm.nih.gove/SNP • Chips for genotyping with 10,000 SNPs • www.moltools.org -- increase genotyping throughput, precision, and improve cost (European) • www.gnome.gov/HapMap 7 Epigenetics • -- DNA sequence is unlikely to be the exclusive source of heritable information – methylation and/or histone arrangement – The epignome – www.epignome.noe.net 8 RNA studies • Presence of any RNA molecule implies that the underlying gene is expressed. • techniques: differential display, SAGE, cDNA arrays, oligonucleotide arrays -- what about EST sequencing???? • transcriptomics • Limitations of arrays -- variability arises from a great number of sequential steps from array preparation • Application -- molecular profiles correlate to disease states -- they can be used as 9 diagnostic tools Protein Studies • "more than 90% of the genome serves no known purpose???" • 30,000 genes produce about 1 million proteins • 10% of the genes have been suggested to encode more than 90% of the proteins • Protein complexity -- comes from: – 40% of human/mouse genes are alternatively spliced – multiple transcription start sites – polyadenlylation and pre-mRNA editing – posttranslational protein modification 10 Proteins cont • www.interaction-proteome.org • www.functionalgenomics.org.uk/section s/resources/protein_arrays.hml • "…some authors claim the human proteome will continue to lie beyond detection threshold of current analytical procedures." 11 Misc • 20,000 knockout strains of yeast have been created • single-gene knockout mutants are commercially available. 12 Systematic Approaches • "biological systems have been broken into simple units and analysed independently." • Not a criticism -- just all that was possible until recently • Phenotype of whole organism "phenome" • Figure -- not terribly insightful • "interpretation of genomic studies in combination with phenotypic data" -challenge of next decade 13 Systematic approaches cont • generic model organism database • www.gmod.org • distributed annotation system DAS • biodas.org -- allows for integration of different databases across the world • Systems biology -- "This approach has thus the potential to reveal unexpected properties of biological systems not accessible by analysing individual molecule classes or 14 separate biological processes." Bioinformatics and In Silico Biology • Information that needs to be analyzed: – 1) genome, DNA, and protein sequences, 2) nucleic acid and protein structures, 3) gene and protein expression data, 4) molecule interactions, and 5) the interaction between integrative biology, systems biology, and literature • BioSPICE -- simulation tools for intra-cellular processes • what is "in silico" biology? • "The next level of complexity is network analysis to detect novel interactions and regulatory connections between genes and groups of genes, in order to understand 15 biological systems." New Journals • PLoS Computational Biology -- 2005 • Claim to fame -- open source 16 Finally -- Concerns about Biotech • food safety related to human health (especially in Europe) • detrimental environmental impact and loss of biodiversity • dissemination of genetically-modified organisms • economic and regulatory concerns over control of biotech by private companies • lack of transparency in food science • ethical concerns about animal welfare • use of gene-related biotech in medical 17 science