Tools for Molecular Genetic Epidemiology: A Comparison of MADGE Methodology with Other Systems

Abstract

The analysis of susceptibility loci for complex genetic diseases has become the focus of much activity in recent years. A key to the successful analysis of these disorders is the analysis of many single nucleotide polymotphisms (SNPs) in extensive population samples to identify DNA variants that are risk factors. As a result, efficient costeffective methods are required for the typing of SNPs. In this review we present an overview of one such method, Microplate-Array Diagonal Gel Electrophoresis (MADGE), and compare it with a number of other methodologies for high throughput SNP typing In disease gene mapping, an essential role is played by the typing of polymorphism between individuals. In the characterization of etiological genetic sites for polygenic disease traits, due to the nature of the genetic contribution to the disease, and thus to the methods of analysis, the number of polymorphic loci needing to be typed is extremely large. Common polymorphism is likely to underpin many common disease susceptibilities. Either guided by linkage studies or by functional hypotheses concerning specific genes, genetic variation in specific genes is examined by association either in family-based or case-control designs (Weeks and Lathrop, 1995). There are two main limitations in the analysis of genetic susceptibility to common disease. The first is that for complex diseases, which have multiple disease-causing