UNIVERSITY OF ALABAMA AT BIRMINGHAM

School of Publich HealthDepartment of Biostatistics

 

Spring 2002

 

BST 675 – Statistical Genetics I

MW 3:30 – 4:45

 

Professor:  Dr. José R. Fernández  

435 Webb Building – (205) 934-2029

jose@uab.edu

 

 

Background

 

After the remarkable achievements of the human genome project, the field of genetics has dramatically increased its importance in clinical areas and biomedical research. The course is aimed to graduate students interested in developing an expertise in statistical genetics or to research-oriented individuals who would like to understand the biological basis underlying statistical approaches for gene mapping.  Students will receive an overview of the field of genetics as an initial exposure to those interested in understanding the process of identifying genes influencing complex traits. Individuals who register for the course must have a basic understanding of statistics and regression models.  Although no prerequisites are established for this course, the sequence BST 601 and BST 602 (or its equivalent) is highly recommended.

During their experience in the course, students will be exposed to principles of Mendelian and molecular genetics, statistics, the use of animal and human models for genetic investigations, and the use of association and linkage techniques to identify genetic influences in population traits.  Also, students will participate in computer lab exercises that will facilitate the understanding of the techniques discussed in class and will demonstrate their application to the identification of genetic influences in complex traits.  

 

Textbook

 

Lynch, M. & Walsh, B.  (1998) Genetics Analysis of Quantitative Traits.  Sunderland, MA:  Sinauers

 

Klug, W.S. & Cummings M.R. (2001) Essentials of Genetics, Fourth Edition.  Upper Sadle River, New Jersey:  Prentice Hall.

 

Optional Recommended Books:

 

Gonic, L. & Smith, W. (1993) The cartoon guide to statistics.  Harper-Collings Publishers, Inc.

 

Gonic, L. & Wheelis, M. (1991) The cartoon guide to genetics.  Harper-Collings Publishers, Inc.

 

 

Grading:

 

Students’ final grade for this course will be based on a total of 100 points, distributed in the following manner:

 

a)        Attendance (7 points): A signing sheet will be passed around during each class to record students’ attendance.  Students will receive .25 point of the final grade for every class they attend except for 1/22 and 2/25.

 

b)       Data Analysis Project (3 points):  This project will account for 3 points of your final grade.  Further details about this project will be provided after the midterm.  This project will be due on 4/3.

 

c)        Midterm (30 points): The midterm exam will consist of 8 questions representing the topics discussed in the course by the time of this exam.  Students will choose 6 questions to be answered.  Each question will have a value of 5 points.  No extra credit will be offered.

 

d)       Final paper  (30 points): A written final paper will be due on May 1st, 2002.   This paper could be done individually or in groups and should follow the style of a manuscript submitted for publication.

 

e)        Oral presentation (30 points):  A 10-20 minute oral presentation is expected for every final paper.  This oral presentation should simulate a talk at a professional meeting.

 

Final Grade will be based on:  A = 100 - 90; B = 89.9 – 80; C = 79.9 – 65; D=64.9 – 50; F = less than 49.9          

 

 

DATE

TOPIC

READINGS

Essentials of Genetics

Genetics and Analysis of QT

Notes

Wed 1/2

Review of Statistics

 

Chapter 2

Guest Lecturer:

Dr. T. Mark Beasley

UAB - Biostatistics

Mon 1/7

Introduction / History of Genetics / Basic Concepts

Chapter 1

 

 

Wed 1/9

Mendelian Genetics and Hardy-Weinberg Equilibrium

Sections 3.1 - 3.7, 22.1 - 22.5

Pages 51-54; 60

 

Mon 1/14

Mitosis, Meiosis and Chromosomal Segregation

Chapter 2

 

 

Wed 1/16

DNA Structure and Central Dogma

Chapter 10

 

 

Mon 1/21

NO CLASS- Martin Luther King Holiday

 

 

 

Wed 1/23

Genetic Markers and Recombinant DNA

Chapter 16

Pages 390-398

Sunnucks (2000)

Mon 1/28

Molecular techniques

Chapter 16

 

Guest Lecturer:

Dr. Mark Shriver

Penn State Univ.

Wed 1/30

Microarrays

Pages 398-399

 

Xiang and Chen (2000)

Mon 2/4

Breeding Crosses in Animal Models (P1, P2, F1, F2, RIs)

Page 37;

Section 22.11

 

 

Wed 2/6

Transgenics, Congenics, Knockouts, tissue-specific knockouts, inducible knock-outs

Section 14.10

Pages 405 - 413

 

Mon 2/11

Multifactorial Inheritance: Genetic Variance

Section 6.1

Pages 61 - 79

 

Wed 2/13

Heritability Estimation

Section 6.3

Pages 170 – 175

 

Mon 2/18

Human Models: Family Structure and Pedigrees

Section 3.9

 

 

Wed 2/20

Twin and Adoption Studies / Review

 

Chapter 19

MacGregor et al. (2000)

Mon 2/25

MID TERM EXAM

 

 

 

Wed 2/27

Linkage, Association, Linkage Disequilibrium, and Haplotype Analysis

Sections 8.1 – 8.2

 

Goldstein and Weale (2001)

Mon 3/4

QTL Mapping

Section 6.4

Pages 321 – 328; 398 – 402; 431 – 436; 442 - 453

Broman (2001)

Wed 3/6

Complexities: Oligogenes, Dominance, Epistasis, Imprinting, Overdominance, etc.

Chapter 4

Pages 82 – 85;

457 - 463

Fernández et al. (2000)

Mon 3/11

LAB Exercise

 

 

 

Wed 3/13

Resemblance Among Relatives

 

Pages 131 – 145

 

Mon 3/18

Linkage:  Sib-Pair Analysis

 

Pages 513 – 521

Amos &  de Andrade (2001)

Wed 3/20

LAB Exercise

 

 

 

Mon 3/25

NO CLASS – SPRING BREAK

 

 

 

Wed 3/27

NO CLASS – SPRING BREAK

 

 

 

Mon 4/1

Discussion of Lab Exercises

 

 

 

Wed 4/3

Data Analysis Project Due

Variance Component Methods

 

Pages 510 - 512

Guest Lecturer: 

Dr. Carol Etzel

MD Anderson Cancer Center

Mon 4/8

TDT: Quantitative Traits

Guest Lecturer:  Dr. David Allison

Pages 419 – 422

Guest Lecturer: 

Dr. David Allison

UAB – Biostatistics;

Allison (1997)

Wed 4/10

MALD

 

 

 

Mon 4/15

Environmental Variation,

Gene x Environment interaction,

Gene by Environment correlation

 

Chapter 6;

Chapter 22

Guest Lecturer: 

Dr. Mark Beasley

UAB – Biostatistics

Wed 4/17

Analysis of Microarray Data

 

 

Guest Lecturer: 

Dr. Grier Page

UAB – Biostatistics

Allison et al. (2001)

Mon 4/22

Oral Presentations

 

 

 

Wed 4/24

Oral Presentations

 

 

 

May 1

FINAL PAPER DUE

 

 

 

 

 

REFERENCES:

 

Allison D. (1997) Transmission-disequilibrium tests for quantitative traits.  American Journal of Human Genetics, 60 (3): 676-690.

 

 Allison, D. B., Gadbury, G., Heo, M, Fernandez, J, Lee, C-K, Prolla, T. A., & Weindruch, R. (in press). A mixture model approach for the analysis of microarray gene expression data. Computational Statistics & Data Analysis.

 

Amos CI & de Andrade M.  (2001) Genetic linkage methods for quantitative traits.  Statistical Methods for Medical Research, 10(1): 3-25.

 

Browman KW (2001)  Review of statistical methods for QTL mapping in experimental crosses.  Laboratory Animal (NY), 30 (7): 44-52

 

Fernández JR, Tarantino LM, Hofer SM, Vogler GP & McClearn GE (2000)  Epistatic quantitative trait loci for alcohol preference in mice.  Behavior Genetics, 30(6): 431-437. 

 

McGregor AJ, Snieder H, Schork NJ & Spector TD (2000)  Twins. Novel uses to study complex traits and genetic diseases.  Trends of Genetics, 16(3): 131-134.

 

Sunnucks P (2000) Efficient genetic markers for population biology Trends in Ecology & Evolution, 15(5): 199-203

 

Xiang CC & Chen Y (2000) cDNA microaary technology and its applications. Biotechnology Advances 18: 35-46.

 

Goldstein DB & Weale ME (2001) Population genomics:  Linage disequilibrium holds the key.  Current Biology, 11: 14 R576-R579.