GENETIC-MARKERS AND MULTIFACTORIAL DISEASES - WHICH STRATEGY TO ADOPT

Genetic markers provide information on the determinism of multifactorial diseases. However the question addressed in those diseases is fundamentally different from the one in monogenic diseases. In the latter case a mutated gene is known to be responsible for the disease and the aim is to identify the primary defect and the involved protein. Thus, genetic markers are used to localize the corresponding DNA sequence. In this context, a systematic search for linkage with random markers is an efficient strategy. For multifactorial diseases - which are not due to a rare mutation, but to the unfavourable combination of several genetic and/or environmental factors the aim is to detect the risk factors involved and to evaluate their effect and interaction. Genes which are functionally related to the disease are then good candidates for risk factors. Focusing on markers of these genes appears to be a more appropriate strategy than using information on random genetic markers. In addition, the marker information does have not to be restricted to the one provided by linkage, but extended to the one on preferential associations between the alleles of the candidate gene and the marker alleles.