1. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-1 Human Genetics Concepts and Applications Eighth Edition Powerpoint Lecture Outline Ricki Lewis Prepared by Dubear Kroening University of Wisconsin-Fox Valley

2. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-2 Chapter 22 Genomics

3. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-3 Genomes An organism’s complete set of chromosomes and genes Instruction manual for individual (species) Genomics  study of genomes

4. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-4 The Human Genome Project Started with linkage maps (now greatly improved) Automated DNA sequencing increased resolution Positional cloning, RFLPs, and SNPs Officially started in 1990, $3 billion, 15 year project Determined the order of the nucleotides present in each of the human chromosomes Draft of the human genome in February 2001 Represents the work of thousands of researchers in an international collaboration

5. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-5 Human Genome Project (ELSI) Recognizing the impact of the human genome project on public policy 3% of the government-sponsored budget was set aside for Ethical, Legal, and Social Issues To prevent misuse of information and genotypic discrimination

6. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-6 Figure 22.1

7. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-7 Sequencing the Human Genome Isolated DNA was broken into smaller pieces and cloned into vectors In the public genome project –Restriction digests of cloned fragments were compared –The order of the pieces along the chromosomes was determined –Subfragments were sequenced and assembled into one continuous sequence

8. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-8 Sequencing the Human Genome (Continued) In the corporate genome project –Fragments were randomly sequenced –The sequences were aligned and assembled into one continuous sequence afterwards –Also used information established in the public project

9. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-9 Sequencing Methods Sanger sequencing – generates fragments (differing by one bp), labeled and read 454 sequencing uses microfluidics, 20 million bases in < 5 hours

10. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-10 Figure 22.2 DNA Sequence Data

11. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-11 Reading a DNA Sequence Figure 22.3

12. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-12 Key Inventions Expressed Sequence Tag (EST) –Enable researches to find protein-encoding genes –cDNAs that are expressed in a particular cell type DNA microarrays –Displays gene expression

13. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-13 Deriving a DNA Sequence Figure 22.4

14. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-14 Techniques Sequences cataloged in public databases called GenBANK Two approaches were used –“Clone by clone” –“Whole genome shotgun”

15. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-15 Figure 22.5a

16. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-16 Figure 22.5b

17. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-17 Sequencing Genomes Figure 22.6

18. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-18 Steps in Genome Sequencing and Analysis Table 22.1

19. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-19 Public Genome Databases Table 22.2

20. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-20 Comparative Genomics List of sequenced organisms is rapidly growing Updated list at www.genomesonline.orgwww.genomesonline.org Looks for conserved sequences that have biological importance Establishing a framework to explain biodiversity and evolutionary events

21. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-21 Figure 22.7

22. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-22 Periodic Table of Genomes Figure 22.8

23. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-23 Figure 22.8

24. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-24 Figure 22.8

25. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-25 Figure 22.8

26. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-26 Figure 22.8

27. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-27 Figure 22.8

28. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-28 Figure 22.8

29. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-29 Figure 22.8

30. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-30 Figure 22.8

31. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-31 Comparative Genomics May Help Us Answer Important Questions Minimal set of genes for life Distinctions between three domains Genes for the simplest eukaryote Basic blueprint for an animal Genes for terrestrial living Birds to mammals Chimps to humans

32. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-32 Genome Uses Comparing sick to healthy to ID genes Examining those at high risk that don’t have the disease to determine why Future treatments based on increased understanding Considerations in having your genome sequenced Encountering genetic technology

33. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-33 Future Figure 22.9