BIMM 110, Spring 2007
Professor Immo E. Scheffler

MOLECULAR BASIS OF HUMAN DISEASE

General Information
Announcements
Course Schedule
Common Techniques and Methods
Problems for Sections (Schedule)

SLIDES

 

"If the true essence of life is the accumulation of experience through generations, then one may perhaps suspect that the key problem in biology from the physicists point of view is how living matter manages to record and perpetuate its experience."
Max Delbruck (Nobel Prize, Physiology and Medicine)
 
"... a person has an inalienable right to know his or her genetic destiny."
Richard Myers (Medical Geneticist and Psychologist)
 
"The concept of genetic disease, enthusiastically appropriated by the medical sciences for complex institutional and economic reasons, represents an expansion of molecular biology far beyond its technical successes.. Today we are being told --and judging from media accounts, are apparently coming to believe-- that what makes us human is our genes. Indeed, the very notion of "culture" as distinct from "biology" seems to have vanished."
Evelyn Fox Keller (Historian of Genetics at Berkeley)

"The whole concept of gene therapy for genetic diseases doesn't fit the business model.."
                                                                  J.M. Wilson, Director of the Inst. for Human Gene Therapy, Univ. of  Penn.

"Disease is a fluid concept influenced by societal and cultural attitudes that change with time and in response to new scientific and medical discoveries."
                                                                      LKF Temple et al. Science 293:807 (2001)

  "The cloning of humans is on most of the lists of things to worry about from Science, along with behaviour control, genetic engineering, transplanted heads, computer poetry and the unrestrained growth of plastic flowers."
  - Lewis Thomas

GENERAL INFORMATION

 

INSTRUCTOR:

Immo E. Scheffler

3330 Bonner Hall

Tel. 534-2741

 e-mail:  ischeffler@ucsd.edu

Lectures:                9 - 9:50 AM in CENTR 101(note the change from the original location).

Office Hours:         flexible;  to be arranged to fit your schedule
 

TAs:                                    

 Saurab Agarwal sagarwal@biomail.ucsd.edu          TU 2-2;50 (WLH2115); W 6-6:50 (SOLIS 109)

Jarrod Heck jheck@ucsd.edu                                 W 4-4:50 and 5-5:50 (SOLIS 109)

Elizabeth Nakae enakae@hotmail.com                    F 8-8:50 (CENTR 217B); F 12-12:50 (U4131)

Mimi Nguyen mnn002@ucsd.edu                            M 2-2:50 (WLH2114)        

Mien Nguyen mtn003@ucsd.edu                             F 1-1:50 (WLH 2206)

Tuan Le ttl003@ucsd.edu                                       F 11-11:50 (CENTR (220)

Michelle Turley mturley@ucsd.edu                           M 11-11:50 (WLH 2114)

 

 

 

 
OBJECTIVES: Virtually every normal and abnormal variation upon the basic human physical condition is the result of the interaction of the genetic make-up of the individual and the environment. The aim of the human genetics segment is to help students gain sufficient understanding of human genetics so that they can appreciate the genetic basis of a large fraction of human diseases, and the importance of genetic considerations in the prevention and treatment of diseases. An introduction to classical genetics and cytogenetics will be followed by a more detailed discussion of the role of molecular genetic techniques in the cloning of genes associated with major inherited diseases, linkage analysis, and the construction of human linkage maps, prenatal diagnosis, and genetic counselling. Furthermore, the cloning of genes has lead to the identification of the function of the proteins encoded by these genes, leading to a deeper understanding of the biochemical and physiological basis of certain genetic diseases. Finally, the availability of cloned genes opens up the prospect of gene therapy.

Family and pedigree information will also be interpreted in genetic terms to predict recurrence risks. A short excursion into population genetics will provide some exposure to concepts such as allele frequencies, linkage equilibrium and disequilibrium, polymorphisms, selection and evolution.

The lectures are supplemented by a problem set. The problems illustrate how the theoretical concepts covered in the lectures can be applied to real situations. Some of the problems also serve simply to re-inforce basic genetic concepts that should be familiar from undergraduate courses. The latter are expected to be particularly helpful for review by non-bio majors.
The problems have been selected by the instructor and tutor, and they cover roughly the first half of the lectures. After some delay, the answers for these problems will be made available in your mailboxes. In practice the tutor, Bridget,  has dealt with the problems, but the instructor is also available for consultations.

Some similar problems will be found on the exam. A common complaint is that "they were not covered in the lectures". Correct, but the concepts needed to answer them WERE covered, OR SHOULD BE PART OF YOUR BASIC KNOWLEDGE OF GENETICS.


TEXTBOOK:    An Introduction to Human Molecular Genetics (2nd Edition)
                           J.J. Pasternak
                           Wiley-Liss 2005
 
(The class does NOT follow a textbook precisely, but the above gives a good introduction to all of the basics; various other textbooks are also suitable for learning the basics. The last half of the lectures will illustrate the powerful new methodologies in molecular genetics and "reverse genetics" by means of several specific examples)   

It has been pointed out repeatedly that all students of human (molecular) genetics should be using the Internet
There are numerous good websites, and the most useful are linked to this page or the following pages of the Web Site for this course:

The KEGG website is excellent for looking up information on Metabolism, Proteins, Genes,
Signalling Pathways, etc.
                    Kyoto Encyclopedia of Genes and Genomes

Online Mendelian Inheritance in Man
                                              (OMIM)
is the best source for information on human genetic diseases (pathology, biochemistry, genetics, etc)

 

"SLIDES"   in almost all lectures a series of slides will be shown (Power Point presentation). The precise number, sequence and content is not fixed until the day before the lecture. At that time these slides will be published on the website. A link will lead you there from each lecture, but to access the slides a password is required (copyrights, etc.). This password will be given out at the beginning of the first lecture.

MIDTERM EXAM:         Wednesday, May 2, 8 - 10 PM in WLH 2001
  

 FINAL EXAM:    Tuesday, June 12, 2007 (absolutely no early exams)

 
AUXILIARY TEXTS: (On Reserve in the Biomed. Library)

6. PRINCIPLES AND PRACTICE OF MEDICAL GENETICS. A.E.H. Emery and D.L. Rimoin, editors; 2nd Edition;     Churchill Livingstone New York 1990; vols. 1 and 2; over 2000 pages !

9.  MEDICAL GENETICS, G.H. Sack, jr., McGraw Hill, New York, 1999.
       this book also comes with a CD-ROM, and it makes a very good attempt to complement and expand the written text with information        available on the Internet (many useful web sites are given).

10. a text book with a complementary WEB SITE that looks very good can be found at UTAH  

    - the following three are good on classical aspects, population genetics, history:

11. TEXTBOOK OF HUMAN GENETICS, M. Levitan, A. Montagu Oxford University Press, New York, London (1971)

12. HUMAN GENETICS, F. Vogel, A.G. Motulsky Springer Verlag, Berlin (1986); Second, Revised Edition

13. THE GENETICS OF HUMAN POPULATION, S,L.L. Cavalli-Sforza, W.F. Bodmer W.H. Freeman and Co. San            Francisco (1971)

- Another excellent set of textbooks or REFERENCE books are:

1. THE MOLECULAR BIOLOGY OF THE CELL (Fourth Edition) by B. Alberts et. al.

2. MOLECULAR CELL BIOLOGY (3rd or newer Edition) by H.Lodish et.al.

An innovative and potentially very useful "TEXT" is becoming available on the Web for learning, catching up, finding definitions, links to the recent literature and much more. It includes the textbook "GENES" and much more (even more to come in the future)

From the virtual text company:         ergito          TRY IT !

 

COURSE SCHEDULE

ANNOUNCEMENTS    (to be updated weekly during the course)

 

LECTURE NO.

 TOPIC
Lectures 1-3 Basic techniques: cloning, restriction mapping, PCR, DNA libraries, nucleic acid hybridizations, DNA sequencing
Lectures 4-5 Genetics in Medicine. Mendelian Genetics in Humans. Inborn Errors of Metabolism. Pedigree Analysis. Genetic Counseling
Lecture 6-7 Complexity of the Human Genome
Lecture 8 Human Cytogenetics. Karyotyping. Chromosomal Abnormalities
Lecture 9 Meiosis, Gametogenesis, Fertilization
Lectures 10-11 Transgenic animals, knock-out mice, cloning of mammals
Lecture 12 Nondisjunctions, Trisomies and Monosomies
Lecture 13 Sex Chromosomes. X-Chromosome Inactivation
Lecture 14-15 Sex Chromosomes. The Y Chromosome and SRY
Lecture 16 Somatic Cell Genetics. Hybrid Cells. Gene Mapping. In situ hybridization
Lectures 17-18 The Human Linkage Map. The complete Human Genome
Lecture 19 Duchennne Muscular Dystrophy
Lecture 20-21 Cystic Fibrosis
Lecture 22-23 Fragile X and Trinucleotide Expansions; Huntington's disease
Lecture 24-25 Mitochondrial Diseases. Maternal Inheritance. Mitochondria, ROS and Aging
Lecture 26 Epigenetics and Imprinting
Lecture 27-28 Genetics of Cancer. Oncogenes, Tumor Suppressors.
Lecture 28 Microarrays and Cancer
Lecture 29 Bioethics and Human Molecular Genetics
Lecture 30 Population Genetics. Hardy Weinberg Law. Linkage Disequilibrium (not given in SP04)

2004 Midterm Exam and Answers

2000 Final Exam and Answers

1999 Final Exam and Answers


 
COMMON TECHNIQUES AND METHODOLOGY USED IN MOLECULAR GENETICS

 The following techniques should be familiar to you, or you should make an effort to find them described in text books. Arrangements will be made to describe, or explain these methodologies as required. In particular, the first Conference will be devoted to this subject.

Most of this material should be familiar to you from your CBB segment on Molecular Biology

WEB SITES:        Primer
                                    Pedro's Tools   (Check it out!)

 1. Electrophoresis of DNA fragments

conventional electrophoresis on agarose or polyacrylamide gels
field inversion gel electrophoresis
pulsed field gel electrophoresis
detection of DNA or RNA by staining or autoradiography
2. Restriction mapping and Southern blots
use of restriction enzymes (specificity)
use of radioactive and nonradioactive probes
hybridization to DNA blots and signal detection
stringency and specificity
 3. Northern blots
conventional
nuclease protection assays
 4. Construction of libraries
vectors: plasmids, phages (lambda), cosmids, YACs (yeast artificial chromosomes),
cDNA and genomic libraries; expression libraries
reverse transcriptase
selections and gene transfer experiments
 5. Screening of libraries
probes
use of antibodies with expression libraries
multiplex screening
selection by genetic complementation
 6. The polymerase chain reaction (PCR)