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Benjamin A. Pierce GENETICS A Conceptual Approach FOURTH EDITION CHAPTER 20 Genomics and Proteomics © 2012 W. H. Freeman and Company Chapter 20 Outline • 20.1 Structural Genomics Determines the DNA Sequences of Entire Genomes, 558 • 20.2 Functional Genomics Determines the Functions of Genes by Using Genomic-Based Approaches, 570 • 20.3 Comparative Genomics Studies How Genomes Evolve, 575 • 20.4 Proteomics Analyzes the Complete Set of Proteins Found in a Cell, 582 20.1 Structural Genomics Determines the DNA Sequences of Entire Genomes • Structural genomics- organization and sequence of genetic information contained within a genome • Genetic maps – (linkage map) approximate locations of genes, relative to the location of other genes, based on the rates of recombination – Limitations • Low resolution or detail • Do not correspond to physical distances between genes 20.1 Structural Genomics Determines the DNA Sequences of Entire Genomes Physical map: based on the direct analysis of DNA, places genes in relation to distances measured in bp, kbp, and mbp 20.1 Structural Genomics Determines the DNA Sequences of Entire Genomes • Sequencing the Entire Genome • The Human Genome Project 20.1 Structural Genomics Determines the DNA Sequences of Entire Genomes • Whole-genome shotgun sequencing: Small-insert clones are prepared directly from genomic DNA and sequenced in a highly automated way. Concept Check 1 A contig is: a. a set of molecular markers used in genetic mapping b. a set of overlapping fragments that form a continuous stretch of DNA c. a set of fragments generated by a restriction enzyme d. a small DNA fragment used in sequencing Concept Check 1 A contig is: a. a set of molecular markers used in genetic mapping b. a set of overlapping fragments that form a continuous stretch of DNA c. a set of fragments generated by a restriction enzyme d. a small DNA fragment used in sequencing 20.1 Structural Genomics Determines the DNA Sequences of Entire Genomes • Single-nucleotide polymorphisms: • A site in the genome where individual members of a species differ in a single base pair • Haplotype: the specific set of SNPs and other genetic variants observed on a chromosome • Linkage disequilibrium • Tag SNPs • Genome-wide association studies 20.1 Structural Genomics Determines the DNA Sequences of Entire Genomes • Copy-number variations (CNV) • The number of copies of DNA sequences varies from people to people. • Expressed-Sequence Tags (ESTs) • Markers associated with DNA sequences that are expressed as RNA • Bioinformatics: • Molecular Biology + Computer Science Concept Check 2 The ab initio approach finds genes by looking for: a. b. c. d. common sequences found in most genes similarity in sequences with known genes mRNA with the use of in situ hybridization mutant phenotypes Concept Check 2 The ab initio approach finds genes by looking for: a. b. c. d. common sequences found in most genes similarity in sequences with known genes mRNA with the use of in situ hybridization mutant phenotypes 20.1 Structural Genomics Determines the DNA Sequences of Entire Genomes • Metagenomics- sequencing genomes of entire communities of organisms • Synthetic Biology-the creation from scratch novel organisms 20.2 Functional Genomics Determines the Functions of Genes by Using Genomic-Based Approaches • Functional genomics • characterizes what the sequences do • Transcriptome: all the RNA molecules transcribed from a genome • Proteome: all the proteins encoded by the genome 20.2 Functional Genomics Determines the Functions of Genes by Using Genomic-Based Approaches Predicting Function from Sequence • Homologous • Genes that are evolutionarily related • Orthologs • Homologous genes in different species that evolved from the same gene in a common ancestor • Paralogs • Homologous genes arising by duplication of a single gene in the same organism Concept Check 3 What is the difference between orthologs and paralogs? a. Orthologs are homologous sequences; paralogs are analogous sequences. b. Orthologs are more similar than paralogs. c. Orthologs are in the same organism; paralogs are in different organisms. d. Orthologs are in different organisms; paralogs are in the same organism. Concept Check 3 What is the difference between orthologs and paralogs? a. Orthologs are homologous sequences; paralogs are analogous sequences. b. Orthologs are more similar than paralogs. c. Orthologs are in the same organism; paralogs are in different organisms. d. Orthologs are in different organisms; paralogs are in the same organism. 20.2 Functional Genomics Determines the Functions of Genes by Using Genomic-Based Approaches • Gene Expression and Microarrays: • Nucleic acid hybridization: using a known DNA fragment as a probe to find a complementary sequence • Gene Expression and Reporter Sequences: • Reporter sequence: encoding an easily observed product used to track the expression of a gene of interest 20.2 Functional Genomics Determines the Functions of Genes by Using Genomic-Based Approaches •Genomewide Mutagenesis •mutagenesis screen 20.3 Comparative Genomics Studies How Genomes Evolve •Prokaryotic Genomes •Genome size and number of genes •Horizontal gene transfer •exchanging genetic information from closely related or distantly related species over evolutionary time •Function of genes 20.3 Comparative Genomics Studies How Genomes Evolve •Eukaryotic Genomes •Genome size and number of genes •Segment duplications and multigene families •Gene deserts •Transposable elements •Protein diversity •Homologous genes •Colinearity between related genomes 20.3 Comparative Genomics Studies How Genomes Evolve •Comparative Drosophila Genomics •The Human Genome 20.4 Proteomics Analyzes the Complete Set of Proteins Found in a Cell • Determination of cellular proteins • Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) • Mass spectrometry 20.4 Proteomics Analyzes the Complete Set of Proteins Found in a Cell • Affinity Capture • interactome • Protein Microarrays • Structural Proteomics