ABSTRACT
In this chapter, the authors describe the principles of linkage analysis and positional cloning because linkage analysis is an important area of genetic thinking that today's students should appreciate, at least in general terms. For rare recessive conditions, autozygosity mapping offers a possible solution. Modern autozygosity mapping uses SNP arrays or whole-genome sequence data. To show how it works out in practice, the authors describe some real examples from pioneering applications of exome sequencing. In countries with high levels of consanguineous marriage, autosomal recessive causes are frequent, and the causative variants may be identified by autozygosity mapping. The study of Vissers and colleagues showed the power of trio analysis for conditions like ID where a high proportion of cases are likely due to de novo mutations. Of the most widely used model organisms, mice are the most likely to show phenotypes directly related to the corresponding human mutation.
