Genetics: From genes to genomes

Entire genetic profiles of individuals will become available This genetic information can be used to help people Make predictions about future possibilities and risks Or, genetic information could also be used to to restrict people's lives Genetic Information Nondiscrimination Act was passed by the federal government in 2008 Prohibits discrimination on the basis of genetic tests by insurance companies and employers

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*Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or displayPowerPoint to accompanyGenetics: From Genes to GenomesFourth EditionLeland H. Hartwell, Leroy Hood, Michael L. Goldberg, Ann E. Reynolds, and Lee M. SilverPrepared by Mary A. BedellUniversity of GeorgiaCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1*Genetics: The study of biological information1.1 DNA: The Fundamental Information Molecule of Life1.2 Proteins: The Functional Molecules of Life Processes1.3 Complex Systems and Molecular Interactions1.4 Molecular Similarities of all Life-Forms1.5 The Modular Construction of Genomes1.6 Modern Genetic Techniques1.7 Human GeneticsCHAPTER OUTLINECHAPTERIntroduction to Genetics in the Twenty-First CenturyCHAPTERCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1*Three levels of biological informationDNAMacromolecule made of nucleic acidsRepository of the genetic codeProteinsMacromolecules made of amino acidsAmino acid sequence determined by DNA sequenceBiological systemsNetwork of interactions between molecules or groups of cellsAccomplish coordinated functionsCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1*The biological information in DNA generates an enormous diversity of living organismsFig. 1.1Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1*Complementary base pairs are a key feature of the DNA moleculeG – C and A – T hydrogen bonds between each strand of the double helixThe two strands of the double helix are in opposite orientationDNA is comprised of four nitrogenous bases [guanine (G), adenine (A), cytosine (C), and thymine (T)], a deoxyribose, and a phosphateFig. 1.2Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1*The information in DNA is one-dimensional and is digitalDNA sequence can be handled by computersAutomated DNA sequencers can sequence about 106 base pairs/dayNew technologies can sequence even more DNA per dayFig. 1.3Biological information is encoded in the nucleotide sequence of DNA and each unit of information is discreteCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1*Organization of genetic information in cellsGenes are sequences of DNA that encode proteinsChromosomes are organelles that package and manage the storage, duplication, expression, and evolution of DNAGenomes are the entire collection of chromosomes in each cell of an organismThe human genome:24 kinds of chromosomes3 x 109 base pairsEncodes 20,000 – 30,000 genesFigure 1.4Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1*Proteins are polymers of hundreds to thousands of amino acidsThere are 20 different amino acidsInformation in DNA of a gene dictates the sequence of amino acids for the proteinThe order of amino acids determines the type of protein and its three dimensional structureDiversity of three-dimensional structure of protein generates an extraordinary diversity of protein functionCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1*The amino acid sequence determines the three-dimensional shape of the proteinChemical formulas for two amino acidsThree-dimensional shapes of two proteinsFigure 1.5aFigure 1.5cCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1*Conversion of biological information from a one- to a four-dimensional stateFig. 1.6Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1*Evolution of biological information on earthRNA may have been the first information-processing moleculeHas ability to store, replicate, mutate, express information, and fold in 3-dimensionsRNA is unstable so other stable macromolecules evolvedDNA took over the linear information and replication functionsProteins took over the 3-dimensional folding functionsAll organisms alive now descended from the first organisms that adopted this molecular specializationCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1*RNA evolved into an intermediary in conversion of DNA information into proteinRNA is comprised of four nitrogenous bases [guanine (G), adenine (A), cytosine (C), and uracil (U)], a ribose, and a phosphateBases are read as triplets to encode amino acid subunits of proteinFig 1.7a Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1*All living organisms use essentially the same genetic codeSpecific triplets of RNA bases encode the 20 amino acidsFigure 1.7bCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1*Many genes have similar functions in different organismsComparison of gene products in different organisms can reveal identical and similar amino acid sequencese.g. cytochrome C protein from six speciesFigure 1.8Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1*A gene from one organism can functionally replace a gene in another organismExample: Pax6 gene is required for eye development in insects, mice, and humansExpression of human Pax6 gene in Drosophila can induce eye development Figure 1.9Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1*Fossil evidence for some of the major stages in the evolution of lifeDuplication and divergence of genetic information is evident in the evolutionary history of lifeTable 1.1Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1*The modular construction of genomesHierarchical organization of information in chromosomesIn eukaryotes, exons are arranged into genesExons from different genes can be rearranged to create new combinationsGenes can duplicate and diverge to create multi-gene familiesMulti-gene families can rapidly expand to create super-familiesRegulatory networks that control gene expression can change rapidlyCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1*Evolution of gene families by duplication of ancestral genesGene duplication followed by sequence divergence underlies the evolution of new genes with new functionsFigure 1.10Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1*Example of the effects of changes to a key regulatory networkTwo-winged flies evolved from four-winged fliesThis evolutionary change was also accomplished in the labMutation of a regulatory network converts a normal two-winged fly into a four-winged flyFigure 1.11Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1*Modern genetic techniquesGenetic dissection of model organismsInactivate a gene and observe the consequencesGenome sequencingHuman Genome ProjectModel organisms and other organismsUnderstanding higher-order processes that arise from interacting biological networksGenomics can rapidly analyze thousands of genesHigh-throughput DNA sequencing and genotypingLarge-scale DNA arrays (chips)Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1*Genomes of five model organisms were sequenced as part of the Human Genome ProjectFigure 1.12Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1*New global tools of genomics can analyze thousands of genes rapidlyFigure 1.13aSchematic drawing of the components of a DNA chipCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1*Hybridization of cDNAs made from cellular mRNAs to a DNA chipFigure 1.13bCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1*Computerized analysis of chip hybridizations can be used to compare mRNA expression in two types of cellsFigure 1.13cThousands of genes can be simultaneously analyzedIn this example, genes whose expression was altered by treatment with an experimental cancer drug were identified using a DNA chipCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1*The focus of this book is on human geneticsGenetics has powerful tools for understanding human biologyParadigm shift from studying one gene or protein at a time to studying interacting networks of many genes and proteinsMolecular studies can lead to predictive and preventive medicineDNA diagnostics can be used to generate a genetic profile of an individualDesign of therapeutic drugs to prevent or minimize symptoms of gene-based diseasesCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1*Important implications of genetics to social issuesEntire genetic profiles of individuals will become availableThis genetic information can be used to help peopleMake predictions about future possibilities and risksOr, genetic information could also be used to to restrict people's livesGenetic Information Nondiscrimination Act was passed by the federal government in 2008Prohibits discrimination on the basis of genetic tests by insurance companies and employersCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1*Important implications of genetics to social issues (continued)Proper interpretation of genetic information and understanding of statistical concepts is essentialRegulation and control of new technology Transgenic technology (genetic engineering) is routine in many animalsShould genetic engineering of human embryos be allowed?Guidelines must be established to prevent misuse of new knowledge in human genetics

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