MOLECULAR BASIS OF HUMAN DISEASE
"The whole concept of gene therapy for genetic diseases doesn't fit the
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)
Immo E. Scheffler
3330 Bonner Hall
Saurab Agarwal email@example.com TU 2-2;50 (WLH2115); W 6-6:50 (SOLIS 109)
Jarrod Heck firstname.lastname@example.org W 4-4:50 and 5-5:50 (SOLIS 109)
Elizabeth Nakae email@example.com F 8-8:50 (CENTR 217B); F 12-12:50 (U4131)
Mimi Nguyen firstname.lastname@example.org M 2-2:50 (WLH2114)
Mien Nguyen email@example.com F 1-1:50 (WLH 2206)
Tuan Le firstname.lastname@example.org F 11-11:50 (CENTR (220)
Michelle Turley email@example.com 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
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)
(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
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.
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 !
ANNOUNCEMENTS (to be updated weekly during the course)
|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
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
Pedro's Tools (Check it out!)
1. Electrophoresis of DNA fragments
conventional electrophoresis on agarose or polyacrylamide gels2. Restriction mapping and Southern blots
field inversion gel electrophoresis
pulsed field gel electrophoresis
detection of DNA or RNA by staining or autoradiography
use of restriction enzymes (specificity)3. Northern blots
use of radioactive and nonradioactive probes
hybridization to DNA blots and signal detection
stringency and specificity
conventional4. Construction of libraries
nuclease protection assays
vectors: plasmids, phages (lambda), cosmids, YACs (yeast artificial chromosomes),5. Screening of libraries
cDNA and genomic libraries; expression libraries
selections and gene transfer experiments
probes6. The polymerase chain reaction (PCR)
use of antibodies with expression libraries
selection by genetic complementation