The localization and identification of human quantitative trait loci
Substantial recent progress has been made in the genomic localization of human quantitative trait loci. Most of these localizations have employed a linkage paradigm using family-based sampling designs. Large extended pedigrees can be shown to be optimal for mapping genes influencing variation in many quantitiatve traits related to common disease risk. In this presentation, I review central issues in the design of QTL localization studies with a focus on variance component-based approaches that are appropriate for both linkage and association analysis. While localization of human QTLs is conceptually straightforward, requiring only large enough samples to be successful, the identification of the genes underlying such QTLs remains difficult. Novel approaches to identification are required such as large-scale transcriptional profiling that is used in tandem with linkage/association information to prioritize positional candidate genes for exhaustive resquencing. Several examples of successful identification of human quantitative trait loci using this marriage of genetic and genomic methods will be provided including the discovery of several novel genes involved in diabetes/obesity risk.