Genomics Bioinformatics

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Genomics Bioinformatics Medicine
http//biochem158.stanford.edu/

• Biochem 158/258 and HumBio 158G

Doug Brutlag Professor Emeritus Biochemistry and
Medicine (by courtesy) brutlag_at_stanford.edu
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Greg Gibson Spencer V. MuseA Primer of Genome
Science
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Greg GibsonIt Takes a Genome
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Course Syllabushttp//biochem158.stanford.edu/
Sept 27 Introduction to Genes, Diseases and Preventive Medicine
Sept 29 Diseases and Disease Databases
Oct 4 Sequencing the Human Genome
Oct 6 Finishing the Human Genome
Oct 11 Next Generation Sequencing Methods
Oct 13 Bioinformatics and Functional Genomics
Oct 18 Sequence Variations in the Human Genome
Oct 20 Structural Variations Insertions, deletions, transpositions, copy number variations.
Oct 25 Discovering Variations Associated with Disease
Oct 27 Discovering Causal Mutations for Disease
Nov 1 Personal Genomics
Nov 3 Stem Cells
Nov 8 Stem Cell Therapies
Nov 10 Gene Expression and Cancer Diagnostics
Nov 15 Epigenetics
Nov 17 Drug Development
Nov 29 Pharmacogenomics
Dec 1 Ethical Issues and Genetic Discrimination
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Course Requirementshttp//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

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Research Projects and Grading Policy
http//biochem158.stanford.edu/
Assignment of Grade Date Due
Inherited Disease Case Presentation 20 Oct. 11
Functional Analysis of a Human Gene 20 Oct. 25
Review of Genome-Wide Association Studies 20 Nov. 8
Final Project on Genomics and Medicine 40 Dec. 9
Second chance on homework!
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Cognate Courses

• Undergraduate Courses
• Biochem 118 Genomics and Medicine Sophomore
  Seminar
• Bio 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 Biology

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BioMedical SeminarsBiomedical Seminars Calendar

• Frontiers in Biology Seminar Series
• Atul Butte, Stanford
• Exploring Systems and Personalized Medicine
  Through Translational Bioinformatics
• Sep 28 400 PM Clark Center Auditorium
• Nick Schork, Scripps
• Functional Genomic Variants and Human Diversity
• Oct 26 400 PM Clark Center Auditorium
• Marisa Bartolomei, U of Pennsylvania
• Epigenetic regulation of genomic imprinting
• Nov 16 28 400 PM Clark Center Auditorium

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Leveraging Genomic Information

• Novel Diagnostics
• Microchips Microarrays - DNA
• Gene Expression - RNA
• Proteomics - Protein

Novel Therapeutics Drug Target
Discovery Rational Drug Design Molecular
Docking Gene Therapy Stem Cell Therapy
Understanding Metabolism
Understanding Disease Inherited Diseases -
OMIM Infectious Diseases Pathogenic
Bacteria Viruses
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Impact of Genomics on MedicineI. 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

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Impact of Genomics on MedicineII. 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

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Impact of Genomics on MedicineIII. Ethical,
Legal and Social Issues

• Personal Privacy
• Insurability
• Employability
• Discrimination
• Genetic selection versus eugenics
• Cosmetic genetics
• Patentability of genes, proteins and other
  natural products

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Impact of Genomics on MedicineIV. 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.

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Preventive Medicine
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Founder of Preventive MedicineLouis Pasteur
When thinking about diseases, I never think
about how to cure them, but instead I think about
how to prevent them.
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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 childs 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

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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.

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Huntington Disease Film
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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 Huntingtons Chorea or Huntingtons 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?