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Genomes

Genomes. Chapter 17. Outline. Genome Maps Genome Sequencing Human Genome Project Genome Geography Variation in the Human Genome Comparative Genomics Functional Genomics Proteomics. Genome Maps.

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Genomes

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  1. Genomes Chapter 17

  2. Outline • Genome Maps • Genome Sequencing • Human Genome Project • Genome Geography • Variation in the Human Genome • Comparative Genomics • Functional Genomics • Proteomics

  3. Genome Maps • Genetic maps show the relative location of genes on a chromosome as determined by recombination frequencies. • measured in centimorgans (cM) • one cM = 0.01% recombination

  4. Genome Maps • Physical maps are diagrams showing the relative positions of landmarks within specific DNA sequences. • measured in base-pairs (bp) • 1,000 base pairs equal 1 kilobase (kb) • use restriction enzymes to cut sequences • use sequenced-tagged sites (STSs) to construct large genome maps

  5. Physical Maps with Restriction Enzymes

  6. Physical Maps with Sequence-Tagged Sites

  7. Genome Sequencing • Sequencing • sequencing of entire genomes now practical due to technological advances • sequencers provide accurate sequences for DNA segments up to 500 bp long • five to ten genome copies sequenced to reduce errors

  8. Sequencing DNA

  9. Genome Sequencing • Artificial chromosomes • vector used in cloning larger pieces of DNA • yeast artificial chromosomes (YAC) • bacterial artificial chromosomes (BAC) • Sequencing by whole genomes • clone-by-clone sequencing - cloning larger inserts in BAC requires construction of a physical map, then placing site of BAC clones for later sequencing

  10. Genome Sequencing • shotgun sequencing - sequence all cloned fragments and use a computer to put together overlaps • requires abundant computing power • does not tie the sequence to any other information about the genome • assembler programs assemble a consensus sequence

  11. Method Comparison

  12. Human Genome Project • Human genome contains 3.2 gigabases • announced on June 26, 2000, that the entire human genome had been sequenced • International Human Genome Sequencing Consortium • draft sequence contains gaps still being filled in

  13. Genome Size and Complexity

  14. Genome Geography • Must now be determined which regions of the genome contain which genes, and what those genes do • Bioinformatics uses computer programs to search for genes, compare genomes, and assemble genomes. • open reading frame (ORF) • expressed sequence tag (EST)

  15. Gene Organization • Four classes of protein-encoding genes are found in eukaryotes. • single-copy genes • segmental duplications • multigene families • tandem clusters

  16. Eukaryotic Noncoding DNA • Six major sorts of noncoding human DNA • noncoding DNA within genes • structural DNA • simple sequence repeats • segmental duplications • pseudogenes • transposable elements • long-interspersed elements (LINEs) • Short-interspersed elements (SINEs)

  17. Variation in the Human Genome • Single nucleotide polymorphisms (SNPs) in the human genome are being used to look for associations between genes. • expect genetic recombination randomizes all but most tightly linked genes • linkage disequilibrium - tendency for genes to not be randomized • can be used to map genes

  18. Comparative Genomics • Comparisons of whole genome maps reveal a large degree of commonality among organisms. • Synteny refers to conserved arrangements of DNA segments in related genomes.

  19. Functional Genomics • Functional genomics is the study of the function of genes and their products. • DNA Microarrays • DNA fragments are deposited on a microscope slide producing DNA microarrays. • SNPs can serve as markers. • screen large numbers of genes extremely quickly

  20. Proteomics • Cataloging and analyzing every protein in the human body • Gene transcripts may not be translated into a protein at any particular moment. • Must study all the RNA present in a tissue at a specific time, transcriptome, as an intermediate step. • Proteomics utilizes new methods to quickly identify and characterize large numbers of proteins.

  21. Using Genomic Information • Genomics revolution has yielded millions of new genes to be investigated. • improvement of medical diagnostics • improvement in agriculture • biological weapons • Potential problems • gene patents • privacy concerns

  22. Summary • Genome Maps • Genome Sequencing • Human Genome Project • Genome Geography • Variation in the Human Genome • Comparative Genomics • Functional Genomics • Proteomics

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