Biology Dept.

DePauw University

Sping 2006
Instructor: Fornari

BIO 415 Lecture

Molecular Genetics

Lecture-MWF 2:15-3:15*Olin 205 or 135*
Lab
-R 9:00-11:50pm*Olin 228A*

Instructor: Chet Fornari
Olin 232, x4781; e-mail: cfornari

Please Note: this course is an elective in
the Biochemistry Program


Instructor: Chet Fornari
Olin 232, x4781; e-mail: cfornari

 

Text: Human Molecular Genetics, (2005) by Jack J. Pasternak, Wiley-Liss Pub.
New Text: The Biology of Cancer (2007) by Robert A. Weinberg
A very useful supplement for the laboratory work: Calculations for Molecular Biology and Biotechnology (2003) by Frank H. Stephenson, Academic Press Pub. (this book is required for the BIO 220/315 course)

Prerequisites: BIO 120/140 or BIO 215; BIO 220 or BIO 315 or instructor's permission


Brief Outline of Course Contents:

I. Chromosome Structure/Function, Transmission Genetics & Linkage;
Basics of the Human Genome & introduction to relevant web-sites and programs

II. DNA polymorphisms, Discovering disease genes by Mapping & Bioinformatics; How are genes for human diseases discovered and identified? The combined approaches are called functional/candidate gene cloning and positional cloning.

III. Advanced Human Genome; Bioinformatics & Population Genetics
IV. The Biochemistry & Genetics of Development & Cancer; applications of gene regulation
V. The molecular genetics of selected diseases.

"Science should be as simple as possible but not simpler."
--Albert Einstein


Description of Course Contents

The first Parts of the course (I, II) focus on basic Transmission Genetics, the structure & function of genes and chromosomes as organized into genomes, along with an introduction to DNA polymorphisms. Essential principles of gene regulation and the basics of signal transduction pathways are also introduced. We do this early in the semester since your understanding of what follows depends on knowing the theoretical genetics, biochemistry, and methods used to generate the data you will be evaluating. So it's important to master this information at the start of the semester; if you accomplish this goal, you will avoid a great deal of confusion as we proceed through the remaining topics. Also, we will try to appreciate more fully the strong connections between the development and use of methods, and the generation of data to support or refute creative hypotheses.

Part III of the course focuses on the Human Genome, and serves to direct our attention to the genes and gene families in our genome that are ultimately responsible for disease. A major emphasis in this Part is the role of transcription factors in the regulation of gene expression. We will review some classic gene systems and examine how they are controlled by specific protein factors (SSDBP's) which bind to specific DNA sites. This part will prepare you for a molecular genetic analysis of development & cancer, (Part IV).

The last part of the course (V) will basically deal with modern Medical Genetics and Molecular Pathology; we will examine the history and genetic causes of certain diseases, and relate this scientific endeavor, experimentally done by candidate gene and positional cloning, to the Human Genome Project.

Throughout the course, we will emphasize experimentation and bioinformtics as the primary means of generating data to test hypotheses; so we will examine the theoretical basis for a variety of methods. You will not be able to design a good experiment or critically evaluate the data in a journal article if you do not understand these methods, along with basic transmission or Mendelian genetics and DNA polymorphisms. Information and discussions from both the lecture and lab will help you to become thoroughly familiar with some of these basic techniques and concepts.

When covering Part IV, development and cancer, we will draw heavily on the role played by transcription factors and signal transduction pathways(Part III); but for Part V, we will use our accumulated understanding of all areas of modern genetics. You can easily see how important it is to keep up with the material, since understanding any one Part depends on how well you mastered the previous one.

 
{Current Reading Assignments and Problems or CRAaP}

Specific topics, with Chapter references:

Chs.
Topics in Sections
Ch.1
Ch.2
Ch.3

PART I - Chromosome Structure/Function & Ideograms; Transmission Genetics, Linkage & Mapping, Human pedigrees; Essentials of the Human Genome

1. Understanding Human Disease: p. 1-14; RQs 1, 3-9
2.
The Genetic System: Chromosomes: p.1-36; RQs 1-10 (all)
3.
The Genetic System: Mendel's Laws & Linkage (with Human Pedigrees); LOD scores; all pages; RQs1-5; 10-13; 15,19,20

Ch.6
Ch.7

 

PART II - Discovering Human Disease Genes by Integrated Mapping
and Bioinformatics

6. Genetic and Physical Mapping of the Human Genome: Gentetic markers, p.153-159; mapping disease genes, p. 159-163; CEPH family panel, p.163-165; putting the disease gene onto the map, p.165-168; genotyping SNPs, p.174-181; the Physical Map and integrating all 3 map types, p.181-186;
CMBB text: ch.12, all pages
Review only: Restriction Enzymes, JJP ch.5, p.108-115; CMBB text, ch.9 , p.186-189 ; Hybridization, JJP ch.5, p.119-122; CMBB text, ch.9, p.212-223
; RQs for ch. 6: 1-6, 8, 9, 13, 15, 20
7. Discovering Human Disease Genes: Cloning Human Disease genes, p.189-191 with fig. 7.2 on p.192; Survey of methods to detect Mutations in Human Genes, p.191-201

Ch.8

Part III - Advanced Human Genome; Bioinformatics; Population Genetics

8. Bioinformatics: Genomics, Functional Genomics, & Proteomics: DiseaseGeneLinks;

Ch.16

PART IV - The Biochemistry & Genetics of Development & Cancer

16. Molecular Genetics of Cancer Syndromes: Introduction to the (1) Cell Biology and Epidemiology of Cancer, (2) the 7 general types of cancers and the properties of cancer cells, and (3) general mechanisms for cancer initiation and progression, p.471-473 and slide set, Part One
Scienftic American article on Herceptin and Dimercept, May 2006 issue
Molecular Mechanisms for Cancer, Signal Transduction Pathways, p.473-477; cell division and apoptosis, p.477-480; oncogenes and tumor suppressor genes, p.482-488
Selected examples only of cancer pathologies (neurofibromatosis, breast cancer, colon cancer, etc.)p. 488-515

X
X
Ch.17

PART V - Genetic Diseases & Molecular Pathology

a. DNA-based diagnosis of genetic diseases; identifying human disease genes
b. Genetically complex human diseases
c.
Working toward human gene therapy
   
   

Grading policies:
(70%): 3 Exams (based on the assigned readings, and lecture/ discussion material):
March 2nd , April 8th (study guide), May 4th; (30%) May 11th Presentations and final Lab Reports due by
(30%):  Lab work, lab reports. class presentation; and Web Project on Human, genetic diseases (see separate syllabus).
top of page

INTERNET SITES & JOURNAL ARTICLES for this course by section: (see lab syllabus for additional sites)

Section
relevant web sites
journal articles
I

UCSC Genome Bioinformatics Ensembl Human

Entrez Genome Project OMIM

GenePalette (requires program installation and registration)

topoSNP

Chromosome Mapping with DNA Markers by R. White & J-M Lalouel in Sci Am 258 #2 Feb 1988

REVIEW ARTICLE: The Genetics of Autism by R. Muhle, S.V. Trentaoste, and I. Rapin, MD in May 2004 Pediactrics 113 #5

REVIEW ARTICLE: The Melanocortin 1 Receptor (MC1R): More Than Just Red Hair by J.L. Rees in Pigment Cell Research 13: 135-140 (2000)

II

Short Tandem Repeat DNA Internet Database

The Biology Project: STR polymorphisms

Beckman-Coulter CEQ Sequencer: STR Genetic Analysis

Chromosome Mapping with DNA Markers by R. White & J-M Lalouel in Sci Am 258 #2 Feb 1988
III
DiseaseGeneLinks  
IV

Genetic Basis of Cancer

New method for Cancer Detection: ROMA

KEGG BRITE Database and KEGG2

Sci Am article on Herceptin and Dimercept, May 2006
Sci Am article on How Cancer Arises 1998
Sci AM article on the Genetic Basis of Cancer 1995
V