340.632.01 METHODS FOR LINKAGE ANALYSIS IN GENETIC EPIDEMIOLOGY

Covers the principles of linkage analysis and introduction to sequencing as used in studies of complex diseases, where both genes and environmental risk factors influence risk. Addresses the principles of both singlepoint and multipoint linkage analysis using ‘model based’ and ‘model free’ statistical methods. Examines the interpretation of genome wide linkage analysis with a particular emphasis on complex and heterogeneous diseases. Introduces the methods for identifying linkage heterogeneity and covariate effects on evidence from linkage analysis as well as combined tests of linkage and linkage disequilibrium in family based tests. Also addresses basic sequencing methods.

This course will prepare you to be able to do the following: • Interpret and critically evaluate published articles on mapping genes for complex phenotypes • Explain the differences between parametric and non-parametric linkage analysis • Explain how linkage models can be extended to test for genetic heterogeneity and gene-gene interaction • Download and implement currently available software for linkage analysis • Explain the conceptual differences between linkage and association as statistical tools to identify genes controlling complex phenotypes • Explain how family based association tests can yield information on linkage in the presence of disequilibrium • Use currently available software to test for linkage in the presence of disequilibrium • Explain how multiple markers can be used as haplotypes or in multipoint mapping • Explain new methods for sequencing analysis • Critically evaluate published articles on haplotype methods for family based tests and contrast these to case-control designs