Chromosomal Location of Human Genetic Diseases
Nowhere is the growth of knowledge about disease- causing mutations in human genes more apparent than in the mapping of their locations to specific sites on individual chromosomes. This progress is documented in twelve published editions of Mendelian Inheritance in Man. A Catalog of Human Genes and Disorders (MIM) by Victor A. McKusick, M.D., at the Johns Hopkins University School of Medicine. Initiated in the early 1960s, its first edition in 1966 contained a total of 1487 entries without a single autosomal gene mapped. This was achieved in 1968 at the time of the second edition (1545 entries). The subsequent editions reveal an entry-doubling time of about 15 years (3368 in the 6th edition (1983), 5710 entries in the 10th edition (1992), 8587 entries in the 12th edition (1998) and 10848 on 21 September 1999 (Hamosh et al., 2000). Since 1987 the McKusick catalog is internationally available online from the National Library of Medicine (Online Mendelian Inheritance in Man, OMIM, see references).

Regularly updated, OMIM has become a major source of information on human genes and genetic diseases. Each entry has a unique 6- digit identifying number and is assigned to one of five catalogs according to genetic category: (1) autosomal dominant, (2) autosomal recessive, (3) X-chromosomal, (4) Y-chromosomal, and (5) mitochondrial. Autosomal entries initiated since 1994 begin with the digit 6. The McKusick catalog has provided a systematic basis for the genetics of man comparable to the first periodic table of chemical elements by Dimitrij I. Mendelyev in 1869 or to the “Chronologisch-thematisches Verzeichnis sämtlicher Tonwerke Wolfgang Amade Mozarts” by Ludwig Alois Ferdinand Köchel in 1862.

A special feature of the McKusick catalog is a map of disease-related gene loci assigned to specific chromosomal sites, called The Morbid Anatomy of the Human Genome. Since this first appeared in 1971 (3rd edition) on a single page, the complete information can no longer be presented in a readable printed version. The map of disease loci presented here on the next five pages, therefore, represents selected entries. For complete information, the reader is referred to the network of data available through OMIM. However, the maps shown on the following pages do provide an overview. More than 1000 disease genes have been mapped as of early 2000. The McKusick catalog also reflects an important difference between customary clinical medicine and medical genetics. Whereas medicine classifies diseases according to their main manifestations, organ systems, age, gender, and other criteria related to the phenotype, medical genetics focuses on the genotype. The gene locus involved, the type of mutation, and genetic heterogeneity provide the basis for disease classification. This expands the concept of disease beyond the clinical manifestation and age of onset (see Childs, 1999).

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