epidemiologia_genetica
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MASTER UNIVERSITARIO EN SALUD PÚBLICA
UNIVERSITAT POMPEU FABRA
UNIVERSITAT AUTÓNOMA DE BARCELONA
Curso 2010-2011
Curso académico: 2010-2011
Asignatura: Principles of Genetic Association Studies
Tipo de asignatura: Optativa
Créditos: 3 ECTS
Profesores: Stefano Guerra, Juan Ramon González
INTRODUCTION Basic contents. The course will focus on the principles, methods, and challenges to dissect the genetics of complex diseases using association studies. Specific topics will be: Epidemiological design strategies for genetic association studies; Selection of positional and/or functional candidate genes; Linkage disequilibrium and population stratification; Allele, genotype, diplotype, and haplotype analyses; Gene-by-environment and gene-gene interactions General aims
1. To provide an overview of the concepts and methods for designing genetic association studies and conducting allele, genotype, haplotype and diplotype analyses
2. To present the software required for analyzing genetic association studies 3. To interpret results derived from a genetic association study 4. To be able to read and critique a paper presenting a genetic association study
EVALUATION The evaluation will be based on:
• Presentation and written critique of one paper on a genetic association study (50%)
• Presentation and written report of an analysis of a real data set (50%) (both will be presented during the last day of classes)
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WORKING PLAN SESSION 1: Introduction to Population and Molecular genetics Date: 25/05/2011
Total time estimated: 4 hours
Objectives: To introduce the concepts of Population and Molecular genetics: Mendelian heredity, genes in population, mechanisms of evolution, Hardy-Weinberg Equilibrium and genetic variability. To describe technologies for the study of genetic basis of disease.
Lecturers: David Comas and Olaya Villa Room: 60.117 Time: 11:00 a 13:00
Plan of activities:
In class (2 hours = 2 hours lectures)
Content Description Time Population genetics Lecture 1 hour
Molecular genetics Lecture 1 hour
At home (2 hours):
Content Description Time ZG Chpt 1 / DT Chpt 2 Read 1 hour
ZG Chpt 4 Read 1 hour
SESSION 2: Basic Principles of Genetic Association Studies Date: 30/05/2011
Total time estimated: 6 hours
Objectives: To introduce the course. To describe challenges in dissecting genetics of complex traits and possible reasons for inconsistencies across previous genetic studies. To describe potentials of genetic association studies and the need for a change in our approach to study the genetic components of complex traits. To introduce different study designs in genetic associations studies and describe strengths and limitations for each of them. To introduce basic concepts of terminology, biological and statistical interaction, with a special emphasis on gene-by-environment interactions.
Lecturer: Stefano Guerra Room: 60.117 Time: 09:00 a 13:00
Plan of activities:
In class (4 hours = 4 hours lectures)
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Content Description Time Introduction: linear versus mutlifactorial approaches Lecture 1 hour
Study design, strengths and limitations of genetic association studies
Lecture 1h 30min
Terminology, biological and statistical interactions,
Gene-by-environment interactions
Lecture 1h 30min
At home (2 hours):
Content Description Time Hand-out readings Read 2 hours
SESSION 3: Analytical Strategies in Genetic Association Studies Part I and Statistical Methods in Genetic Association Studies Date: 01/06/2011
Total time estimated: 8 hours
Objectives: To introduce Mendelian inheritance and the importance of HWE in genetic association studies. To introduce differences in approaches and methodologies to study monogenic diseases versus complex traits. To describe advantages and limitations of linkage disequilibrium in genetic association studies. To introduce statistical methods in genetic association studies
Lecturer: Stefano Guerra, Juan Ramón Gónzalez Room: 60.117 & 61.307 Time: 09:00 a 13:00
Plan of activities:
In class (4 hours = 4 hours lectures)
Content Description Time Mendelian inheritance and the importance of Hardy-Weinberg Equilibrium in genetic association studies
Lecture 1h
The importance of Linkage Disequilibrium in genetic association studies
Lecture 1h
Statistical methods in genetic association studies Lecture 2h
At home (4 hours):
Content Description Time ZG Chpt 2, 3, 9 Read 4 hour
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SESSION 4: Haplotype analysis and computer lab session Date: 06/06/2011
Total time estimated: 6 hours
Objectives: To introduce haplotype phase ambiguity. To introduce software to perform genetic association studies.
Lecturers: Stefano Guerra, Juan Ramón Gónzalez Room: 60.117 & 61.307 Time: 09:00 a 13:00
Plan of activities:
In class (4 hours = 1 hour lecture + 3 lab sessions)
Content Description Time Haplotype ambiguous phase Lecture 1 hour
Statistical software to perform genetic association studies: Descriptive, HWE, SNP association, SNP interaction, haplotype analysis and haplotype interaction
Lab session 3 hours
At home (2 hours):
Content Description Time ZG Chpt 10, 12 Read 2 hours
SESSION 5: Analytical Strategies in Genetic Association Studies Date: 08/06/2011
Total time estimated: 6 hours
Objectives: To introduce gene selection (positional versus functional candidate gene and genome-wide associations studies), genome-wide strategies, Mendelian randomization. To introduce principles of allele, genotype, haplotype, and diplotype analyses.
Lecturers: Stefano Guerra Room: 60.117 Time: 09:00 a 13:00
Plan of activities:
In class (4 hours = 4 hours lectures)
Content Description Time Gene selection, genome-wide strategies, Mendelian randomization
Lecture 1h 30min
Principles of allele, genotype, haplotype, and diplotype analyses
Lecture 1h 30min
Overview Lecture 1 hour
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At home (2 hours):
Content Description Time ZG Chpt 10, 12 Read 2 hours
SESSION 6: Paper critique presentations and Computer lab session Date: 15/06/2011
Total time estimated: 9 hours
Objectives: To evaluate student’s critiques of selected papers addressing genetic association studies. To evaluate student's capability of analyzing and interpreting genetic association Studies on a dataset that will be given to students in Session 4.
Lecturers: Stefano Guerra, Juan Ramón Gónzalez Room: 60.117 Time: 09:00 a 13:00
Plan of activities:
In class (4 hours = 2 hours seminar + 2 hours lab session)
Content Description Time Paper critique presentation Seminar 2 hours
Data analysis presentation Lab session 2 hours
At home (5 hours):
Content Description Time To prepare presentation 5 hours
BIBLIOGRAPHY
• Ziegler & König: “A Statistical Approach to Genetic Epidemiology” [ZG]
• Khoury, Little, and Burke: “Human Genome Epidemiology” [KLB]
• Duncan Thomas: “Statistical Methods in Genetic Epidemiology” [DT]
LECTURERS
Stefano Guerra received his Medical Degree in 1996 from the University of Milan, where he also completed a fellowship in pulmonary medicine. Subsequently, he completed a Master in Public Health (concentration area in epidemiology) and a PhD in Epidemiology with minor in Genetics (2003) at the University of Arizona in Tucson. Over the last eight years, he has taught graduate courses in genetic epidemiology at the University of Arizona
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and at the Universitat Pompeu Fabra. His main research focus is on identifying genetic and molecular profiles for development and progression of asthma and chronic obstructive pulmonary disease (COPD) and, to that purpose, he is involved in the design and conduct of several long-term cohort studies on respiratory diseases.
Juan Ramón Gonzalez obtained his BSc (1997) in Biostatistics at Autonomous University of Barcelona. Then he got his MSc (2000) and PhD (2006) in Statistics at Technical University of Catalonia. He was working at the Catalan Institute of Oncology (ICO) from 1997 until 2005 as a biostatistician. Since July 2005 he has been working at the Centre for Genomic Regulation (CRG) as a researcher at Xavier Estivill’s lab. In July 2007 he moved to the Centre for Research in Environmental Epidemiology (CREAL) getting a research position in biostatistics. Since 2006 he is an associate professor of biostatistics at the Department of Public Health of University of Barcelona (UB). Currently, his work focuses on genetic epidemiology. He is mainly interested in statistical methods to identify genetic causes of complex disorders. Joint with other colleagues, we have developed software for genotype and haplotype association analysis in genetic association studies. We also developed a model to predict mutations in deafness. He is also interested in methods for determining alterations in gene dosage (CNVs).
Contact
Stefano Guerra Centre de Recerca en Epidemiologia Ambiental (CREAL) Parc de Recerca Biomédica de Barcelona (PRBB) C/Doctor Aiguader nº88 Barcelona 08003 Planta 1 Despacho 183.11 Tel: 93 214 73 29 http://www.creal.cat [email protected]
Juan Ramon González Centre de Recerca en Epidemiologia Ambiental (CREAL) Parc de Recerca Biomédica de Barcelona (PRBB) C/Doctor Aiguader nº88 Barcelona 08003 Planta 1 Despacho 188 Tel: 93 316 06 72 http://www.creal.cat http://www.creal.cat/jrgonzalez [email protected]