Recent advances have made it feasible to incorporate data on potential genetic risk factors into traditional epidemiological studies. Hence, there is an increasing need for epidemiologists to understand the genetic basis of disease, read and interpret genetic studies, and incorporate the collection and analysis of genetic information into studies of disease etiology.

The objectives of this course are to provide epidemiologists with an understanding of: (1) basic genetics, (2) the "tools" used by geneticists and genetic epidemiologists, and (3) the integration of genetic data into traditional epidemiological study designs. After completing this course, students will be able to read and interpret genetic epidemiological studies. In addition, they will be able to design epidemiological studies that incorporate genetic data collection and analysis.

Laura Mitchell, Ph.D.

Room 926, Blockley Hall

Phone: 215-573-6167, Fax: 215-573-2265

Email: lauramit@mail.med.upenn.edu

Timothy Rebbeck, Ph.D.

Room 904, Blockley Hall

Phone: 215-898-1793, Fax: 215-573-2265

Email: trebbeck@cceb.med.upenn.edu

Lecturers:

Format: The class will meet weekly for 2.5 hours (Tuesdays, 2-4:30). The first half of the semester will be devoted to a series of lectures covering the basic principals (e.g. Mendelian inheritance) and practices (e.g. bio-sampling and laboratory methods) that distinguish genetic epidemiology from traditional epidemiology. The remainder of the semester will focus on the types of studies that are typically used in genetic epidemiology. This portion of the class will consist of short lectures followed by critical appraisal of relevant literature.

Location: Room 940 Blockley Hall

Credits: 1 course unit

Prerequisites: Permission of course director (L. Mitchell or T. Rebbeck).

Reading: Original articles will be used. Background reading will be made available as needed.

Evaluation: 1) Class participation, 2) Homework, 3) Final exam

1. Introduction to Genetic Epidemiology

1/16 Lecture 1: Overview of Human Genetics (L. Mitchell, K. Nathanson, T. Rebbeck)

Review of meiosis, recombination and linkage. Mendelian patterns of inheritance.

1/23 Lecture 2: Overview of Human Genetics (L. Mitchell, K. Nathanson, T. Rebbeck)

Review of additional genetic concepts (e.g. genotype, phenotype, penetrance, expressivity, linkage, multifactorial inheritance) and nomenclature (e.g. genotypes, haplotypes).

Homework #1

1/30 Lecture 3: Overview of Genetic Epidemiology and Human Population Genetics (L. Mitchell)

Epidemiology versus genetic epidemiology, goals of genetic epidemiology.

Hardy-Weinberg Law, estimation of genotype and allele frequencies, testing for HWE, linkage equilibrium/disequilibrium.

Homework #2.

2/6 Lecture 4: Basic Concepts in Genetic Epidemiology (L. Mitchell)

Familial aggregation, complex traits, major genes, susceptibility loci, gene-environment interactions.

Homework #3

2/13 Lecture 5: Data Collection (T. Rebbeck and J. Stopfer)

Methods for, and logistics of collecting family data and DNA. Constructing a pedigree, confirmation of clinical diagnosis, and collection of biological specimens.

Review of Homework #1

2/20 Lecture 6: Biomarkers and Laboratory Methods (T. Rebbeck)

Overview of laboratory methods used to obtain genetic data (e.g microsatellites, SNP, PCR) and DNA banking.

Review of Homework #2

2/27 Lecture 7: Ethical Issues (J. Merz)

Informed consent, IRB concerns, DNA banking.

Review of Homework #3

3/6 Lecture 8: Segregation Analysis. (Y. Yao).

Overview of the goals of segregation analysis, strengths and limitations, interpretation of published studies.

3/13 Spring Break

3/20 Lecture 9: Parametric linkage Analysis (T. Rebbeck)

Overview of parametric linkage analysis, strengths and limitations, interpretation of published studies.

3/27 Lecture 10: Nonparametric Linkage Analysis (R. Spielman)

Overview of nonparametric linkage analysis, strengths and limitations, interpretation of published studies.

4/3 Lecture 11: Case-Control Studies (P. Kanetsky)

Overview of case-control studies. Special considerations in the design of case-control studies using genetic data (e.g. population stratification), genotypes versus alleles, evaluation of gene x gene and gene x environment interactions.

4/10 Lecture 12: Case-Series Studies (T. Rebbeck)

Evaluation of the case-series design for evaluating gene x gene and gene x environment interactions.

4/17 Lecture 13: Family based methods for detecting associations (L. Mitchell)

Overview of family based tests of association, comparison with case-control studies, evaluation of interactions.

4/24 Lecture 14: Examples of Genetic Epidemiological Studies (L. Mitchell, T. Rebbeck)