ABSTRACT
While it has been difficult to directly identify the genes underlying obesity in humans, animal models clearly have important advantages for both genetic and biochemical studies. Evidence for Mendelian inheritance in human obesity has been provided by studies of families, twins, and adoptees. The two basic approaches to identifying the genes underlying complex diseases such as obesity can be called “phenotype down” and “genotype up”. The genotype up approach is the second major approach to identify genes underlying obesity. Unfortunately, traditional positional cloning approaches are difficult to use in human studies of complex polygenic traits such as obesity. This chapter concentrates on genotype up methods for the identification of loci underlying obesity and its risk factors by surveying the entire genome of experimental animal models. The methods used for phenotyping will depend on the trait of interest. Blood pressure is influenced by multiple genetic loci, and efforts to identify these loci in human subjects have been largely unsuccessful.
