Mapping complex traits in diseases of the hair and skin

The past decade has witnessed the ascendance of human genetics in modern medicine, and at the forefront of this movement is the identification of genetic factors underlying inherited diseases. The methods of genetic mapping and positional cloning have made the discovery of genes with alleles that cause simple Mendelian diseases commonplace. The elucidation of the genetic basis of such disorders has vitalized both human genetics and the entire medical community as the field has gained prominence. The fact remains, however, that diseases resulting from the action of alleles of a single gene comprise only a minor percentage of traits that are medically relevant to humanity. The majority of these are multifactorial "complex traits", which result from the aggregate contribution of an unknown number of genes interacting with each other and with the environment. The current challenge has become one of parlaying successes in the mapping of Mendelian diseases into the discovery of genes whose alleles predispose the development of a complex disease. In light of this challenge, this review summarizes the methods and addresses some of the central issues of complex trait mapping, while using examples from dermatologically-relevant complex traits such as psoriasis and alopecia. Additionally, current technical and theoretical advances as well as the potential impact of the Human Genome Project will be discussed.