Applied Genetic Modeling: Winter 2004

Biomathematics 207B/ Biostatistics M237 / Human Genetics M207B

Instructor: Dr. Janet Sinsheimer, , 5-8002

Room 5357C (Gonda) or AV-628 (CHS)

Office Hours: by appt.

TA: Vladimir Minin, Biomathematics

Applied genetic modeling introduces the statistical methods used in the analysis of familial studies of disease. Lecture 2 hours (Thursday 11am-1pm), Computer laboratory 2 hours (Tuesday 11-1pm) Lab held in CHS A1-269.

Prerequisites: Coursework in undergraduate statistics equivalent to Biostatistics 110A and 110B or the consent of the instructor. Basic genetic concepts will be covered during the first lecture (no prerequisite knowledge of human genetics required).

Laboratory Fee: $20 (includes copy of GAP - student version).

Evaluation: Course grade will be based on a project (55%), an in class midterm exam (35%) and homework and class participation (10%). The project will consist of data analysis summarized as a (seven page) paper written in the style of a journal article. Lab and lecture attendance and participation will also be taken into account in the grading.

Primary Texts:

M. J. Khoury, T. H. Beatty, B. H. Cohen, Fundamentals of Genetic Epidemiology. Oxford University Press, New York (1993).

P. K. Sham, Statistics in Human Genetics, Arnold applications in Statistics, Oxford University Press, New York (1998).

GAP Manuals, Epicenter Software, PO 90073, Pasadena CA 91109, (818) 304-9487

SAGE Manuals, version 3.1 Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland Ohio.

Supplementary Texts:

L. Gonick and M. Wheelis, The Cartoon Guide to Genetics, Harper Collins Publishers. New York, New York (1996).

B. H. Liu, Statistical Genomics: Linkage Mapping and QTL analysis. CRC Press (1998).

K. Lange, Mathematical and Statistical Methods in Human Genetics, Second Edition, Springer-Verlag (2002).

J. Ott, Analysis of Human Genetic Linkage. The Johns Hopkins University Press, Baltimore (1991).

T. Strachan and A. P. Read, Human Molecular Genetics. John Wiley and Sons, Inc. New York (1999).

K. M. Weiss, Genetic Variation and Human Disease. Cambridge University Press, New York (1993).

Tentative Topics and Schedule:

Date Topic

"Week" 1 - 1/8/04 Fundamental Genetic Concepts / Fundamental Statistical Concepts.

(1/8/04 and 1/13/04) On Tuesdays, we meet in the computer laboratory Room A1-269

(Bring 3” floppy or zip disk to Lab each week)

Week 2 - 1/15/04 Familial Aggregation / Multivariate Regression Analysis

Week 3 - 1/22/04 Segregation analysis Part I - Does the trait act in a genetic manner?

Week 4 - 1/29/04 Segregation analysis Part II - What is the best genetic model?

Genetic model based linkage analysis

Week 5 - 2/5/04 Genetic model based and genetic model free linkage analysis

Week 6 - 2/12/04 Genetic Model free linkage analysis

Week 7 - 2/19/04 MIDTERM EXAM 2/19/04 (covers through 2/12/04 inclusive)

Genetic Model free methods continued.

Week 8 - 2/26/04 Family Based Association Tests

Week 9 - 3/4/04 “Advanced Topics” - Genotype error checking, building a genetic map, variance components

Week 10 – 3/11/04 Advanced topics continued

Seven page paper due by Wednesday noon of finals week (3/24/04). Drop off paper at the Biostatistics Office (5th floor) or to room 5357C Gonda.