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genetics.doc Document Transcript

  • 1. BIOLOGY 215 GENETICS Spring 2003 mous pea experiments about 1900. The middle of the 20th century saw the birth of molecular genetics, as re- Bruce Wightman searchers connected the dots be- Shankweiler 224 tween biochemistry and Mendelian wightman@muhlenberg.edu genetics. The end of the 20th century x3254 saw the birth of genomics—an infor- mation-oriented approach that com- bined the power of computers and information technology with genetic data. This course will focus primarily Lecture and discussion meets Tues- on issues that are explicitly genetic— day and Thursday from 9:30-10:45 many applications of genetics are AM in Shankweiler 109. also covered in Molecular Biology, Cell Biology, Developmental Biology, Lab sections meet on Tuesday or Neuroscience, and Microbiology. We Wednesday afternoons, as sched- will emphasize genetics as it is used uled, from 1:30-4:20 PM in as a tool for inquiry—this is an aston- Shankweiler 230. ishingly fast-moving area of science. The course will treat both population and experimental approaches to un- derstanding genetic mechanisms. We will perform laboratory experi- ments that reflect current procedures and the experimental approaches of Genetics is the discipline that studies genetics, in addition to purely educa- the nature of biological diversity and tional exercises to illustrate concep- inheritance. In essence, Genetics tual points made in class. No class concerns itself with two major ques- focusing on an active area of scien- tions: 1) What are the mechanisms tific research is complete without for determining diversity within a some treatment of primary scientific species? 2) What are the mecha- literature. Therefore, we will be read- nisms by which biological character- ing selected papers that focus on ge- istics are inherited by offspring? Hu- netic issues, with a special emphasis mans have practiced manipulative on human genetics. My principle aim genetics since antiquity, millennia is to attempt both breadth of cover- before it became a scientific disci- age, from population to molecular pline. For example, early humans se- genetic approaches, and depth, with lectively bred animals and plants for specific forays into more detailed ex- agricultural purposes, and many had amples of how genetics is used to inbreeding taboos. The scientific learn more about biology. study of genetics began with the re- discovery of Gregor Mendel’s fa-
  • 2. SCHEDULE DATE DAY TOPIC READING 14-Jan Tu Introduction; variation, genetics and environment Ch. 1 16-Jan Th Mendelian genetics in humans pp 40-52 21-Jan Tu Gene interactions Ch. 4 23-Jan Th Discussion 28-Jan Tu Chromosomes and inheritance Ch. 3; Ch. 17 30-Jan Th Aneuploidy Ch. 18 4-Feb Tu Mutation Ch. 15-16 6-Feb Th Mutation 11-Feb Tu Population genetics Ch. 24 13-Feb Th Population genetics 18-Feb Tu Discussion 20-Feb Th Quantitative genetics Ch. 25 25-Feb Tu Evolutionary genetics Ch. 26 27-Feb Th Gene mapping Ch. 5; pp 404-7 11-Mar Tu Gene mapping 13-Mar Th Gene mapping Ch. 6 18-Mar Tu Discussion 20-Mar Th Bacterial genetics Ch. 7 25-Mar Tu Bacterial genetics 27-Mar Th EXAM 1-Apr Tu Bacterial genetics pp 283-290 3-Apr Th Discussion 8-Apr Tu Gene cloning pp 372-384 10-Apr Th Genetic engineering pp 418-427 15-Apr Tu Discussion 17-Apr Th Genomics Ch. 14 22-Apr Tu Genomics 24-Apr Th Discussion 29-Apr Tu Recombination mechanisms pp 586-592 1-May Th Transposons Ch. 20 Reading refers to specific chapters or pages in Griffiths et al., 7th edition.
  • 3. EVALUATION Your final grade will be determined based on your performance on exams, as- signments, participation, attendance, and laboratory. The weighting of these dif- ferent components will be as follows: 15% Mid-term exam 20% Final exam 20% Take-home assignments 25% Laboratory assignments and participation 15% Discussion and lecture participation 5% Homework Grades will be assigned based on the familiar, if arbitrary, 90-100 A range, etc. ASSIGNMENTS For the lecture component of the course, there will be regular assignments of two types: weekly homework and longer take-home assignments. The former will be collected, assigned simple credit, and returned. These assignments will be drawn primarily from problems in the textbook. Over the course of the semester, you will be given four or five longer take-home assignments. These assignments will be typewritten and graded. The explicit nature of these assignments will be provided when each is assigned. For the laboratory component of the course, there will be approximately six re- ports due over the course of the semester. Most will be of modest length. DISCUSSIONS Over the course of the semester there will by six meetings devoted entirely to discussions. Most or all of these sessions will focus on primary literature. You will be assigned to help lead the discussion of one session, along with three or four of your peers. Everyone must read the papers assigned and come to class pre- pared to discuss the paper. Have questions and observations in mind. What question are the authors addressing? What genetic approaches are employed? What are the implications of the study? What are the problems with the study?
  • 4. BIOLOGY DEPARTMENT SEMINARS All students are strongly encouraged to attend the Biology Seminar Series regu- larly. Biology Department seminars are held on Tuesday or Wednesday after- noons at 4:30 PM in Shankweiler 109. Specific seminars, especially those that relate to genetics, will be announced in class. TEXTBOOK Griffiths, J. F., et al., 2000, An Introduction to Genetic Analysis, 7th Ed., New York: WH Freeman. This textbook is absolutely required for the course and available for sale in the bookstore. OFFICE HOURS My nominal office hours will be MWF 10-11 AM, and Tu 11-11:30 AM. I’m likely to be in my office or nearby in one of the labs any day between 9:30 AM and 4:30 PM. I also encourage you to email me with questions. POLICIES All assignments are due on the date indicated. Late assignments will result in a significant penalty. Each exam must be taken on the date and time scheduled. Exceptions to these policies will be allowed only in the case of serious illness or family emergency. All exceptions must be pre-approved by the instructor and documented by a physician or other official. Cheating will not be tolerated in any form. Trying to obtain “answers” from stu- dents who took this course in years past is an ABC violation, and in any case will hurt you in the long run (this is really a course about questions). Keep in mind that all written work handed in for this course must be your own. In most cases, you may discuss assignments with your peers or me, but the written work submit- ted must be your work alone. In the case of the longer take-home assignments, all work must be your own, signing the ABC pledge will indicate your compliance in not discussing the assignment with anyone else. Attendance is expected at every class. If you cannot attend a particular class, it is your responsibility to obtain notes from a classmate. Students with documented disabilities should discuss appropriate accommoda- tions with me as soon as possible.
  • 5. ASSUMED KNOWLEDGE The prerequisite for BIO 215 is the three semester Principles of Biology core se- quence. For students who have not completed this sequence due to transfer, non-traditional or cross-registration status, this equates to complete mastery of the contents of Biology, by Campbell and Reece, or its equivalent. Specifically, students should be completely proficient in basic Mendelian genetics, which will NOT be covered in any detail in this course. Examples of terminology and con- cepts that will be assumed include, but are not limited to: allele Chi-square analysis recombinant DNA gene penetrance vector, plasmid, etc. trait expressivity transformation characteristic linkage basic biochemistry dominant sex-linkage genetic code recessive meiosis Central Dogma semidominant mitosis lac operon codominant recombination basic gene regulation TENTATIVE OUTLINE My current vision for the conceptual flow of the course is indicated in the sched- ule on page 2. A more detailed outline of the concepts we will cover follows, but is subject to change. i. histones I. Variation, genetics and environment ii. heterochromatin a. genetic variation iii. loop domains and b. genetic and environmental de- puffs terminism e. genome sequence organization c. genetic nomenclature i. repetitive DNA d. genetic ratios and probability ii. transposons e. lethal alleles iii. VNTR and centromer- f. Chi-square test ic sequences II. Human Mendelian genetics iv. spacer DNA and III. Gene interactions genome organization a. complementation analysis b. epistasis f. changes in chromosome struc- c. suppression ture d. enhancement i. mechanisms of e. animal coat color example change IV. Chromosomes and inheritance ii. deletions iii. duplications a. meiotic segregation and life cy- iv. inversions cle v. translocations b. alternating haploid-diploid c. chromosome structure vi. position effect varie- i. centromeres gation ii. telomeres V. aneuploidy iii. nucleoli a. ploidy and variation iv. banding patterns i. monoploidy d. chromatin and chromosome ii. polyploidy compaction b. human aneuploidies
  • 6. VI. mutation i. founder effect a. natural sources of mutation ii. directional selection b. mutation induction b. adaptive peaks i. mutagens c. speciation c. selections and screens d. evolution of genes i. suppressor screens i. changes in ploidy ii. reversion screens ii. gene duplication iii. enhancer screens iii. horizontal transfer iv. sensitized background iv. rates of molecular d. measuring mutation rates evolution; molecular e. types of mutations clocks i. point, forward, reverse X. Gene mapping (reversion), null, a. linkage revisited leaky, frameshift, non- b. recombination sense, missense, c. sex-linkage differences silent, insertions, dele- d. genetic maps and linkage tions e. three-point testcross f. interference ii. morphological, lethal, conditional, temp- g. mapping with molecular mark- sens, biochemical, ers; RFLP analysis protorophic, aux- h. tetrads and octads otrophic, lof, gof, hy- i. mitotic recombination and mo- pomorphic, hypermor- saic analysis phic, neomorphic, ma- j. other mapping techniques ternal effect, zygotic i. in situ analysis effect ii. somatic cell hybrids VII. Population genetics XI. Microbial genetics a. allele frequency a. Hfr gene mapping in bacteria b. types of polymorphism b. bacteriophage genetics; rII sys- c. sequence polymorphism tem d. Hardy-Weinberg c. gene mapping by transduction e. sources of variation i. mutation d. genetic fine structure; intra- ii. recombination genic recombination iii. migration XII. Gene cloning a. vectors iv. inbreeding and assor- b. libraries tative mating v. selection c. cloning by functional comple- 1. fitness mentation 2. rate of d. positional cloning change e. cloning by tagging XIII. Genetic engineering 3. artificial se- a. animal engineering lection b. human gene therapy vi. balanced polymor- c. molecular genetic diagnostics phism XIV. Genomics f. human populations and the a. structural genomics concept of race i. physical mapping VIII. Quantitative genetics ii. genome sequencing a. statistical measures b. functional genomics b. genotype and phenotype distri- i. two-hybrid approach- bution es c. norm of reaction and phenotyp- ii. microarrays ic distribution iii. proteomics d. heritability XV. Recombination mechanisms a. chiasmata e. QTL’s and mapping quantita- b. Holliday model tive genes XVI. Transposition IX. Evolutionary genetics a. McClintock a. variation and divergence of b. bacterial transposons populations
  • 7. c. eukaryotic transposons; P ele- ments