1. Doug Brutlag 2011 Genomics Bioinformatics & Medicine http://biochem158.stanford.edu/ http://biochem158.stanford.edu/ Biochem 158/258 and HumBio 158G Doug Brutlag Professor Emeritus Biochemistry and Medicine (by courtesy) brutlag@stanford.edu

2. Doug Brutlag 2011 Greg Gibson & Spencer V. Muse A Primer of Genome Science A Primer of Genome Science $62

3. Doug Brutlag 2011 Greg Gibson It Takes a Genome

4. Doug Brutlag 2011 Course Syllabus http://biochem158.stanford.edu/ http://biochem158.stanford.edu/ Sept 27Introduction to Genes, Diseases and Preventive Medicine Sept 29Diseases and Disease Databases Oct 4Sequencing the Human Genome Oct 6Finishing the Human Genome Oct 11Next Generation Sequencing Methods Oct 13Bioinformatics and Functional Genomics Oct 18Sequence Variations in the Human Genome Oct 20Structural Variations: Insertions, deletions, transpositions, & copy number variations. Oct 25Discovering Variations Associated with Disease Oct 27Discovering Causal Mutations for Disease Nov 1Personal Genomics Nov 3Stem Cells Nov 8Stem Cell Therapies Nov 10Gene Expression and Cancer Diagnostics Nov 15Epigenetics Nov 17Drug Development Nov 29Pharmacogenomics Dec 1Ethical Issues and Genetic Discrimination

5. Doug Brutlag 2011 Course Requirements http://biochem158.stanford.edu/ http://biochem158.stanford.edu/ Four research assignments –Disease case presentation –Bioinformatics analysis of gene function –Description of a genome-wide association study –Final project (paper or presentation) on The molecular basis of a disease A novel diagnosis or treatment of a disease A technological advance in genomics & disease An ethical, legal or social issue in genomics or medicine Participation in Class Discussion

6. Doug Brutlag 2011 Research Projects and Grading Policy http://biochem158.stanford.edu/ http://biochem158.stanford.edu/ Assignment% of GradeDate Due Inherited Disease Case Presentation20%Oct. 11 Functional Analysis of a Human Gene20%Oct. 25 Review of Genome-Wide Association Studies20%Nov. 8 Final Project on Genomics and Medicine40%Dec. 9 Second chance on homework!

7. Doug Brutlag 2011 Cognate Courses Undergraduate Courses Biochem 118 Genomics and Medicine Sophomore Seminar Bio 109A and 109B (HumBio 158A and B) The Human Genome and DiseaseBio 109A and 109B (HumBio 158A and B) The Human Genome and Disease HumBio 157 The Biology of Stem Cells HumBio 159 Genes and Environment in Disease Causation Graduate Level Courses Genetics 210 Genomics and Personalized Medicine Genetics 211 Genomics CS 262 Computational Genomics CS 273A A Computational Tour of the Human Genome Biochem 218/BMI 231 Computational Molecular Biology BMI 214/CS 274 Representations and Algorithms for Computational Molecular BiologyBMI 214/CS 274 Representations and Algorithms for Computational Molecular Biology

8. Doug Brutlag 2011 BioMedical Seminars Biomedical Seminars Calendar Biomedical Seminars Calendar Frontiers in Biology Seminar Series Atul Butte, Stanford Exploring Systems and Personalized Medicine Through Translational Bioinformatics Sep 28 4:00 PM Clark Center Auditorium Nick Schork, Scripps Functional Genomic Variants and Human Diversity Oct 26 4:00 PM Clark Center Auditorium Marisa Bartolomei, U of Pennsylvania Epigenetic regulation of genomic imprinting Nov 16 28 4:00 PM Clark Center Auditorium

9. Doug Brutlag 2011 Leveraging Genomic Information Novel Diagnostics Microchips & Microarrays - DNA Gene Expression - RNA Proteomics - Protein Understanding Metabolism Understanding Disease Inherited Diseases - OMIM Infectious Diseases Pathogenic Bacteria Viruses Novel Therapeutics Drug Target Discovery Rational Drug Design Molecular Docking Gene Therapy Stem Cell Therapy

10. Doug Brutlag 2011 Impact of Genomics on Medicine I. Diagnostics Genomics: Identifying all known human genes Functional Genomics: Functional analysis of genes –In what tissues are they important? –When in development are the genes used? –How are they regulated? Novel diagnostics –Linking genes to diseases and to traits –Predisposition to diseases –Expression of genes and disease Personal Genomics –Understanding the link between genomics and environment –Increased vigilance and taking action to prevent disease –Improving health care

11. Doug Brutlag 2011 Impact of Genomics on Medicine II. Therapeutics Novel Drug Development –Identifying novel drug targets –Validating drug targets –Predicting toxicity and adverse reactions –Improving clinical trials and testing Gene therapy –Replacing the gene rather than the gene product Stem cells therapies –Replacing the entire cell type or tissue to cure a disease Pharmacogenomics –Personalized medicine –Adjusting drug, amounts and delivery to suit patients –Maximize efficacy and minimize side effects –Identify genetics of adverse reactions –Identify patients who respond optimally

12. Doug Brutlag 2011 Impact of Genomics on Medicine III. Ethical, Legal and Social Issues Personal Privacy Insurability Employability Discrimination Genetic selection versus eugenics Cosmetic genetics Patentability of genes, proteins and other natural products

13. Doug Brutlag 2011 Impact of Genomics on Medicine IV. Strategic Genomics can discover disease associated genes Genomics can discover disease causing genes. Genomics provides understanding of disease Genomics and bioinformatics provides basis for novel drug development Genomics provides basis for novel genetic and stem cell therapies Genomics provides the basis for preventive medicine.

14. Doug Brutlag 2011 Preventive Medicine

15. Doug Brutlag 2011 Founder of Preventive Medicine: Louis Pasteur When thinking about diseases, I never think about how to cure them, but instead I think about how to prevent them.

16. Doug Brutlag 2011 Preventive Medicine The goal is to prevent disease from occurring. First one must identify the cause of the disease. Treat the cause of the disease rather than the symptoms –Example 1: Peptic Ulcers –Example 2: Pyrogens Genomics identifies genetic causes of inherited disease. When Paul Wise (a Stanford pediatrician) heard that we may soon sequence every child’s genome at birth, he stated: –“… all medicine may soon become pediatrics!” Overlooked accidents, infectious disease, auto immune disease and aging: environmental or acquired diseases Genetic penetrance and environment

17. Doug Brutlag 2011 Health Care Policy Current health care treats disease rather than maintaining health (Illness care?) Future health care prevent disease Reduce need for expensive interventions Need policies that incentivize patients and doctors to prevent disease. Need social pressures to control behavior and increase vigilance.

18. Doug Brutlag 2011 Huntington Disease Film

19. Doug Brutlag 2011 The Inheritance You are 18 years old. Your father abandoned you and your mother when you only 2 years old. Your father died this year and left you an inheritance. He died from an autosomal dominant disease known as Huntington’s Chorea or Huntington’s Disease. You have a 50% chance of inheriting this invariably fatal neurodegenerative disease. But there is a genetic test for this disease that can tell you not only if you have the disease, and if you do, when you will die from it. Would you take the genetic test or not? Why?