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Physiological Genomics Condensed notes from class, including extras from slides and mentioned in class!

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Physiology 3140A
Jane Rylett

Physiological Genomics 1 Genetic Control of Cell PhysiologyCellular Physiology Trying to understand how cells function Mammals have hundreds of different cell types each with unique biological roles and specialized properties These differences shape size function have to be taken into account when studying cell functionMost of the neurons in the brain no longer proliferate Two main processes required for a mature healthy organism Cell multiplicationTheseprocessesaredrivenbytheproliferation cellsgeneticprogramandtheinteractionsofthecellwithitsCell specializationenvironmentThissectiondealswithdifferentiation thecontrolofcellularbehaviourbygenesandtheconsequencesofthese eventsforthebiologyoftheorganism For each cell doubling this information must be duplicated in the process of DNAreplicationCell CycleReplication coupled to cell division through cell cycleReplication occurs in S phase synthesisCell division including equal distribution of DNA intothe two daughter cells occurs in the M Phase mitosisM and S phases separated by two Gap phases G1 cell decides what to do next proliferatedifferentiate die or not do anything and G2 prepares for mitosisNothing much goes on in G phasesG2 shorter than G1most decisions make in G1 but G2 can make emergency decisions tooGenes are individual units of DNA that encode functional molecules such as proteins and certain RNAsInformation stored as DNA is transcribed into RNA and messenger RNA mRNA is translated into proteinsFunctional information DNA info directly controls function of its gene products cells and organismDNA replication and mitosis ensure that all cells within an individual organism have identical genetic material eg nucleotide sequence with minor exceptionsVariety in cell types appearance and function achievedCell types defined by pattern of functional molecules mostly proteins in the cellsExample muscle cells contain many contractile proteins neuronal cells synthesize specific receptors and neurotransmitters and intestinal cells secrete specific digestive enzymesAll cells of a multicellular organism have the same genetic information but only a subset of material is active when certain genes are expressed in a given cellAs cells specialize during development pattern of gene expression becomes more specialized and restrictedInformation types in DNAFunctional info coding sequence determines structurefunction of gene productsRegulatory info controls whenwhere gene expressed additional regulatory info packaged in DNAThis info is very conserved within a species all humans have a very similar nucleotide sequence Specialization achieved at a molecular level through regulatory informationMuch of the info on which genes are active in a given context is contained in the DNA sequenceSequences regulate when and where a gene is switched on or off in response to external stimuli the level of gene expression changes etc ThreeDimensional Structure of DNA Chromatin and NucleosomesNucleosome DNA wrapped around histone octamerDNA Folding o Euchromatinrelaxed o Heterochromatinhighly foldedInverse relationship between gene expression and folding and methylation of DNA2 The Human GenomeGenetic Factors ControlDevelopment of physiological systems tissue architecture morphologyFunctional properties eg which receptors of channels are expressed and active in a particular cellGenetic Factors Contribute to most DiseasesGerm line mutations directly give rise to diseases cystic fibrosisGenetic variances polymorphisms contribute to the risk for common diseases eg diabetes cardiovascular diseases Alzheimers disease arthritisSomatic mutations responsible for most cancersGenetic factors control our response to exogenous substances such as drugs o Some drugs work only in patients with a certain genetic makeup o Other drugs have severe side effects in people with specific genotypesKnowledge of Genetic Principles and the Human Genome are thus Necessary ForUnderstanding of the development and homeostasis of organs and organismsIdentification of pathophysiological leading to diseasePersonalized medicine design of novel preventive diagnostic and therapeutic approachesLed to design of the Human Genome Project publication of complete sequence in 2001Human Genome ProjectDesigned to sequence the entire human genomeCompleted in 2001 by two groups o International Human Genome Sequencing Consortium Publicly Funded Nature o Venter et al Company funded privately Science
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