Understanding how genetic variation causes disease can be like climbing a mountain. Such diseases tend to be rare and include cystic fibrosis and Huntington disease. Complex disorders, on the other hand, are quite different.
Complex disorders are common and subsume massive 'pie-slices' of healthcare budgets.
They include type 2 diabetes, asthma and Alzheimer's disease. They represent the greatest challenge to human genetics. This is demonstrated by the fact that no genes have yet been proven to cause complex disorders in humans, and only two have been reported in rodents. Through a sophisticated, detailed, original and painstaking approach, these investigators have implicated a gene that confers risk for type 2 diabetes, a gene with little by way to render it an obvious candidate. The classic approach to identifying a gene whose mutation causes a monogenic trait is through a method called 'positional cloning', so called because it relies on narrowing down the position of the gene to a point wherein the implicated chromosomal interval is so small that it houses only a few genes.