Lecture+1+I.+Introduction+1-4-10

Lecture+1+I.+Introduction+1-4-10 - Welcome to BIS101-001...

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Unformatted text preview: Welcome to BIS101-001 Winter 2010 Genes and Gene Expression Dr. S.D. O’Neill, Professor Mon - Wed 10:00 a.m. - 11:50 a.m. 1003 Giedt Hall BIS101-001 Winter 2010—Genes and Gene Expression, S.D. O’Neill © 2010 BIS1012010— O’ BIS101 BIS101 is a survey of the fundamental BIS101 concepts of genetics and molecular biology including vocabulary, technology, experiment design, with particular emphasis on gene structure and function. Prokaryotic and eukaryotic molecular models will be used to demonstrate basic principles of gene mapping, chromatin structure, genomics, replication, transcription, translation, mutations, repair, gene regulation and genetic engineering. BIS101-001 Winter 2010—Genes and Gene Expression, S.D. O’Neill © 2010 BIS1012010— O’ Business Textbook: Introduction to Genetics by Griffiths et Textbook: al., 9th edition. Genetics — From Genes to Genomes — Hartwell Genetics et al., 3rd Edition. Grade based on 400 points distributed among two Grade midterms, each worth 100 points and a final exam worth 200 points. Requests for regards should be submitted to the Requests Teaching Assistants using a Petition for Regrade Form obtained on SmartSite. Past grade distribution is as follows: 18% As, 33% Past Bs, 29% Cs, 10% Ds and 8% Fs. Zero tolerance for cheating Zero BIS101-001 Winter 2010—Genes and Gene Expression, S.D. O’Neill © 2010 BIS1012010— O’ Exam Policy There will be no early, late or makeup There exams. A valid medical excuse is the only basis for missing an exam or for petitioning for an incomplete (I) grade. In the case of missed midterm exams, the final exam will be weighted an additional 100 points. Sixty (60) minutes are allotted to each midterm exam. BIS101-001 Winter 2010—Genes and Gene Expression, S.D. O’Neill © 2010 BIS1012010— O’ Let’s get started… Biological information is encoded in DNA Biological (genotype). Biological function is the result of proteins Biological and RNAs (phenotype). Complex biological systems are the result of Complex gene networks and interactions involving DNA-Protein, Protein-Protein, RNA-Protein). All life forms use similar mechanisms to All regulate genes. The modular nature of the genome facilitates The rapid evolution Powerful analytical tools (genomics) and a Powerful “systems” approach, permits the dissection of the complex genetic processes for the benefit of humankind. BIS101-001 Winter 2010—Genes and Gene Expression, S.D. O’Neill © 2010 BIS1012010— O’ Topic I. Introduction A. Genetics is the study of inheritance -offspring resemble their parents Goals of Genetics: 1. to explain heredity 2. explain variation Genetics also is defined by the study of “genes.” BIS101-001 Winter 2010—Genes and Gene Expression, S.D. O’Neill © 2010 BIS1012010— O’ What is a gene? B.Gene What is it? -functional unit of heredity (that carries information from one generation to the next) -structural unit of heredity, -segment of DNA (sequence composed of a transcribed region and a regulatory sequence that makes transcription possible) BIS101-001 Winter 2010—Genes and Gene Expression, S.D. O’Neill © 2010 BIS1012010— O’ How to study genes Three branches of Genetics, all study genes: 1. Transmission genetics (classical genetics)- study of the transmission of genes from generation to generation 2. Molecular genetics-structure and function of genes at the molecular level. 3. Population genetics-distribution and behavior of genes within populations 4. We will focus our attention on transmission genetics and molecular genetics, with a genomics approach whenever possible and appropriate. BIS101-001 Winter 2010—Genes and Gene Expression, S.D. O’Neill © 2010 BIS1012010— O’ The Central Dogma C. The Central Dogma: The theory that explains the flow of genetic information in a cell. Textbook takes a historical look at genetics beginning with the days before such things as genes were understood; back in the mid-1800s at the time of Gregor Mendel, the founder of the science of genetics. However, we will discuss genetics knowing that a gene is a gene functional sequence of DNA that encodes genetic information. The Central Dogma for the flow of genetic information is below: Central replication transcription translation DNA DNA RNA protein The information carried in the DNA, RNA and protein result in a particular trait or character of an organism. We will study this process in detail during Part 2 of the course. BIS101-001 Winter 2010—Genes and Gene Expression, S.D. O’Neill © 2010 BIS1012010— O’ Genotype and Phenotype D. Genotype vs. Phenotype: Genotype- genetic make-up of an organism 1. 2. same genotype = same genes For a given individual, genotype is fixed for a lifetime (except for mutation and epigenetic effects) -generally unchanged by the environment starting point or the potential for structure/function potential 3. Phenotype- physical form of an organism (the outward manifestation of a genetic trait) Can be considered at all levels: individual tissue/cell molec. level organism liver/organ proteins (structural/enzymes) BIS101-001 Winter 2010—Genes and Gene Expression, S.D. O’Neill © 2010 BIS1012010— O’ Phenotype 1. Same phenotype = same look or function alike. 2. May change throughout lifetime Example: hair color in humans -affected by the environment - especially nutrition has major effect (e.g., height/weight). 3. Product of interaction between genes and environment. BIS101-001 Winter 2010—Genes and Gene Expression, S.D. O’Neill © 2010 BIS1012010— O’ Course Objective Course objective:To understand the true Course relationship between genotype and phenotype Definition of Genotype: The actual alleles Definition (alternation forms of a gene, or sequence of DNA) in an individual. Definition of Phenotype: An observable Definition characteristic (produced by the genotype). Challenge: The path from genotype to Challenge: phenotype is not a straight line! BIS101-001 Winter 2010—Genes and Gene Expression, S.D. O’Neill © 2010 BIS1012010— O’ Biological Complexity The path from genotype to phenotype is complex and non-linear so we must consider the complexity of biological systems when we study genetics. BIS101-001 Winter 2010—Genes and Gene Expression, S.D. O’Neill © 2010 BIS1012010— O’ Filters of Genetics Variation i cs n et n tio tri i ge Nu Ep GENOTYPE GENOTYPE re u ult C e tyl s fe Li PHENOTYPE PHENOTYPE PHENOTYPE Life span Because of these gene modifiers, we do not have to be slaves to our genes nor do we have to be victims of genetic determinism. March 30, 2009 BIS101-001, Spring 2009—Genes and Gene Expression, R.L. Rodriguez ©2009 BIS1012009— From Genotype to Phenotype Genetic Variation March 30, 2009 BIS101-001, Spring 2009—Genes and Gene Expression, R.L. Rodriguez ©2009 BIS1012009— What is the source of phenotypic differences? National Museum National Single Nucleotide Polymorphism (SNP) of History March 30, 2009 BIS101-001, Spring 2009—Genes and Gene Expression, R.L. Rodriguez ©2009 BIS1012009— Alleles, SNPs and Heterozygosity Allele 1 Allele 1 Allele 1 Allele 1 G-C G-C C-G C-G A-T A-T A-T A-T T-A T-A T-A T-A A-T A-T C-G C-G G-C G-C C-G C-G C-G C-G T-A T-A A-T A-T A-T A-T C-G C-G G-C G-C C-G C-G A-T A-T A-T A-T T-A T-A T-A T-A A-T A-T C-G C-G G-C G-C C-G C-G C-G C-G T-A T-A A-T A-T A-T A-T C-G C-G Allele 1 Allele 2 Allele 1 Allele 2 G-C G-C C-G C-G A-T A-T A-T A-T T-A T-A T-A T-A A-T A-T C-G C-G G-C G-C C-G C-G C-G C-G T-A T-A A-T A-T A-T A-T C-G C-G G-C G-C C-G C-G A-T A-T A-T A-T T-A T-A T-A T-A A-T A-T T-A T-A G-C G-C C-G C-G C-G C-G T-A T-A A-T A-T A-T A-T C-G C-G Allele 1 Allele 3 G-C C-G A-T A-T T-A T-A Slide 10 A-T C-G G-C C-G C-G T-A A-T A-T C-G A-T C-G A-T A-T T-A T-A A-T C-G G-C C-G C-G T-A A-T T-A C-G Allele 4 Allele 4 2 Allele3 A-T G-C C-G A-T A-T T-A T-A A-T T-A G-C C-G C-G T-A A-T A-T C-G A-T C-G A-T A-T T-A T-A A-T T-A C-G G-C C-G C-G T-A A-T A-T C-G March 30, 2009 BIS101-001, Spring 2009—Genes and Gene Expression, R.L. Rodriguez ©2009 BIS1012009— Genomics and Predictive, Preventative, Personalize Medicine 2002 — The National Institutes of Health 2002 and Celera Genomics release of working drafts of the human, (rice genome was also released that same year. The human genome will lead The us to predictive, preventive and personalized medicine. March 30, 2009 BIS101-001, Spring 2009—Genes and Gene Expression, R.L. Rodriguez ©2009 BIS1012009— The Human Genome: A summary 3.4 billion base pairs distributed among 23 distinct chromosomes 4-6 million differences between any two individuals ↓ ↓ ↓↓ ↓ ↓ March 30, 2009 BIS101-001, Spring 2009—Genes and Gene Expression, R.L. Rodriguez ©2009 BIS1012009— Complex biological systems emerge from regulatory networks March 30, 2009 BIS101-001, Spring 2009—Genes and Gene Expression, R.L. Rodriguez ©2009 BIS1012009— Complex biological systems emerge from regulatory networks Key Information Control Points March 30, 2009 BIS101-001, Spring 2009—Genes and Gene Expression, R.L. Rodriguez ©2009 BIS1012009— From Genotype to Phenotype Environment x Gene Interactions (Lifestyle,Diet, Behavior, Culture, Socioeconomic Status) March 30, 2009 BIS101-001, Spring 2009—Genes and Gene Expression, R.L. Rodriguez ©2009 BIS1012009— Environment x Gene Interactions Pima Indians in the US Pima and in Mexico have the same genetic background. Pimas of Arizona have a Pimas T2DM rate approaching 50% for individuals over 45. Pimas of Mexico have Pimas T2DM rates similar to US whites (~7%). The principle differences The between these two groups are diet and physical activity. March 30, 2009 BIS101-001, Spring 2009—Genes and Gene Expression, R.L. Rodriguez ©2009 BIS1012009— From Genotype to Phenotype Epigenetics/Epigenomics (a state of gene functionality that is not encoded in the DNA but is still heritable from one generation to the next and maintained through chemical modification of DNA) March 30, 2009 BIS101-001, Spring 2009—Genes and Gene Expression, R.L. Rodriguez ©2009 BIS1012009— Dissecting Environment from Genetics Identical or monozygotic (MZ) Identical twins have the same genetic material. This make twins ideal for This studying environmental affects. At the left are DNA profiles from At four sets of twins. Which are MZ? March 30, 2009 BIS101-001, Spring 2009—Genes and Gene Expression, R.L. Rodriguez ©2009 BIS1012009— Dr. Robert J. Huskey, University of Virginia Huskey, Affects of Epigenetic Drift on Phenotype March 30, 2009 BIS101-001, Spring 2009—Genes and Gene Expression, R.L. Rodriguez ©2009 BIS1012009— From Genotype to Phenotype Genomic Architecture: Genetic Admixture March 30, 2009 BIS101-001, Spring 2009—Genes and Gene Expression, R.L. Rodriguez ©2009 BIS1012009— What about “genetic admixture”? Mexican American Health Professions Organization: Ashley L. Garcia, president; Lizette Gonzales, public relations; Carlos Cruz, treasurer; Elizabeth Salinas, vice president; Monique Rodriguez, secretary March 30, 2009 BIS101-001, Spring 2009—Genes and Gene Expression, R.L. Rodriguez ©2009 BIS1012009— Genetic Admixture — Latinos African Native American European = “Mestizos” Courtesy E. Burchard-Gonzalez Burchard- March 30, 2009 BIS101-001, Spring 2009—Genes and Gene Expression, R.L. Rodriguez ©2009 BIS1012009— Genetic Origins of Latino Ethnic Groups 100% 90% 80% 70% 7 24 52 19 African Native American European Percent Ancestral Contribution Admixture 60% 50% 40% 30% 20% 10% 0% 57 41 Choudhry S, et. al: 2006 Mexican American Puerto Rican March 30, 2009 BIS101-001, Spring 2009—Genes and Gene Expression, R.L. Rodriguez ©2009 BIS1012009— Complex phenotypes are due to many factors Complex Environmental Signals Schadt and Lum, 2006. J. Lipid Res. 47:2601-17 Schadt and Lum, 2006. J. Lipid Res. 47:2601Lum, Res. 47:2601-17 Complex phenotypes Epigenetic modifications: Epigenetic modifications: March 30, 2009 BIS101-001, Spring 2009—Genes and Gene Expression, R.L. Rodriguez ©2009 BIS1012009— Reverse Engineer Genetic Networks From Genotype to Phenotype From Genotype to Phenotype Integrative Genomics: A Holistic View External Input Epigenotype Genotype Genome Regulatory networks modulated by signal transduction pathways RNAi microRNA transposons Regulatory networks modulated by chromatin remodeling (i.e. methylation, acetylation) Gene expression Gene expression Gene expression Phenotype / Health Outcomes Phenotype Phenotype Phenotype March 30, 2009 BIS101-001, Spring 2009—Genes and Gene Expression, R.L. Rodriguez ©2009 BIS1012009— The Single Gene/Magic Bullet Paradigm Magic Bullet (drug) Gregor Mendel 1822-1884 Paul Ehrlich 1854-1915 Gene Gene Gene Gene Product Product Disease Disease Phenotype Phenotype March 30, 2009 BIS101-001, Spring 2009—Genes and Gene Expression, R.L. Rodriguez ©2009 BIS1012009— The “Systems” Approach to Biological Processes “Systems” All the other genes All the other genes I Idon’t know about, don’t know about, I Idon’t care about don’t care about Gene B Gene D Gene A Gene C Gene E List of ALL genes Biological Processes interactions Pathways Networks List of metabolites 1990 2008 March 30, 2009 BIS101-001, Spring 2009—Genes and Gene Expression, R.L. Rodriguez ©2009 BIS1012009— Systems Biology and Health (Chapter 12) Systems biology is the application of “omic” technologies (genomics, proteomics, metabolomics, informatics, combinatorial chemistry, etc.) to the studying biological processes. Unlike traditional biology which examines single genes or proteins in isolation, systems biology simultaneously studies the complex interaction of many levels of biological information - genomic DNA, mRNA, proteins, functional proteins, metabolites and informational pathways and networks - to understand the true relationship between genotype and phenotype. As biology becomes and information-rich science, the challenge will be to transform data into knowledge and knowledge into applications that will promote global health and a clean and stable environment. March 30, 2009 BIS101-001, Spring 2009—Genes and Gene Expression, R.L. Rodriguez ©2009 BIS1012009— Systems biology integrates all the “omics” transcriptome protein proteome genotype Informatics gene gene expression profiling informational networks metabolome March 30, 2009 BIS101-001, Spring 2009—Genes and Gene Expression, R.L. Rodriguez ©2009 BIS1012009— What are the “omic” sciences? Genomics Structural Genomics Functional Genomics Metabolomics Comparative Genomics Proteomics Nutritional Genomics Glycomics Transcriptomics Lipomics Physiological Genomics Whateveromics March 30, 2009 BIS101-001, Spring 2009—Genes and Gene Expression, R.L. Rodriguez ©2009 BIS1012009— Chapter 1: The Study of Biological Information Biological information, fundamental to life, is Biological encoded in DNA. DNA is an ideal “information” molecule DNA Genomics is the high-throughput, massively Genomics parallel analysis of the structure, function and regulation of all genes in a cell or organism. Genomics make genetics an information-rich Genomics science March 30, 2009 BIS101-001, Spring 2009—Genes and Gene Expression, R.L. Rodriguez ©2009 BIS1012009— BIS101 Lecture Material Acknowledgments: Acknowledgments: Thank you to Professor Raymond L. Rodriguez for permission to use some of his lecture slides. Please respect the copyright nature of this material. BIS101-001 Winter 2010—Genes and Gene Expression, S.D. O’Neill © 2010 BIS1012010— O’ ...
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This note was uploaded on 02/10/2010 for the course BIS BIS 101 taught by Professor Sanders during the Winter '09 term at UC Davis.

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