1. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-1 Human Genetics Concepts and Applications Seventh Edition Powerpoint Lecture Outline Ricki Lewis Prepared by Mary King Kananen Penn State Altoona

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

4. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-4 The Human Genome Project Decade-long project to sequence the human genome Determined the order of the nucleotides present in each of the human chromosomes The draft of the human genome was announced 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 Early Techniques Sequencing the human genome built on linkage and cytogenetic information from previous work Positional cloning –Identifying parts of the genome corresponding to a genetic disorder –Uses RFLP mapping of linked SNPs Reading 22.1 describes how the Huntington disease gene was discovered

7. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-7 Figure 22.1

8. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-8 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

9. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-9 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

10. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-10 Sanger Sequencing Method A DNA template is used to synthesize a new labeled DNA molecule Uses polymerase and nucleotides –a mix of regular deoxyribonucleotides (A, G, C and T) plus one dideoxyribonucleotide Addition of regular nucleotides allows continued DNA formation Addition of a dideoxyribonucleotide stops the DNA formation A dideoxyribonucleotide lacks the chemical group required to add new nucleotides to the DNA chain

11. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-11 Sanger Sequencing Method (Continued) If dideoxyadenosine is used as the chain terminator –Multiple DNA molecules are made, all ending in adenosine –If the template does not have adenosine at a specific length there will be no molecules of that length in the test tube This process is repeated separately with G, C and T dideoxynucleotides Computer compares fragments and sequences the DNA

12. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-12 Sequencing DNA Figure 22.2

13. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-13 Figure 22.3 DNA Sequence Data

14. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-14 Reading a DNA Sequence Figure 22.4

15. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-15 Key Inventions Expressed Sequence Tag (EST) –Enable researches to find protein – encoding genes –cDNAs that are expressed in a particular cell type DNA microarrays –Display cDNAs

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

17. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-17 Techniques Sequences cataloged in public databases called GenBANK Two approaches were used –“Clone by clone” –“Whole genome shotgun”

18. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-18 Figure 22.6a

19. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-19 Figure 22.6b

20. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-20 Sequencing Genomes Figure 22.7

21. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-21 Steps in Genome Sequencing and Analysis Table 22.1

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

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

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 Periodic Table of Genomes Figure 22.9

26. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-26 Figure 22.9

27. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-27 Figure 22.9

28. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-28 Figure 22.9

29. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-29 Figure 22.9

30. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-30 Figure 22.9

31. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-31 Figure 22.9

32. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-32 Figure 22.9

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

34. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-34 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

35. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-35 Future Figure 22.10

36. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 22-36 How Will Genome Information Affect you?