ABSTRACT
Technological advances made in molecular biology in the last 10-20 years have profoundly influenced the manner in which the etiology o f disease is investigated. Nowhere is this more apparent than in the study of the genetic basis o f human disease. To date, genes (or mutations) influencing a number of diseases whose biochemical defects were unknown at one time have been either physically isolated or localized to a small region in the human genome (i.e., the collective genetic material possessed by each o f us) by taking advantage o f modem laboratory methods (1,2). Although the molecular tools that paved the way for the localization, or “mapping,” o f these genes were unthinkable only some 25 years ago, their development does not tell the whole story. Equally important to the development o f any technology is its proper application or implementation. In this review, we describe contem porary and successful strategies for the detection and localization o f genes that depend on modem molecular genetic technologies. We want to empha size that this review focuses not on the technologies themselves, but rather on the ways in which one can exploit them to map genes influencing a disease or phenotype o f interest. In addition, we do not review strategies one might use to determine whether a disease or phenotype is under genet ic control (i.e., heritability or segregation assessment). With this in mind, the primary question to be addressed in this review is not “how can one determine if a disease is genetic?” but “how can one find the genes in-
fluencing a disease known to have a genetic component?” Since an under standing o f a few basic concepts in genetics is required for this purpose, we offer a brief summary o f some necessary terms. We also offer tables listing studies that make use o f the strategies described. For readers interested not only in the application o f modem gene mapping methods, but also in the details o f the requisite laboratory methods, we suggest any of the contem porary textbooks describing the biological basis o f modem recombinant DNA methods (3-5).
