Evolution of MIM/OMIM from a Catalog of Mendelian Phenotypes to a Catalog of Human Genes and Genetic Disorders
The first print edition of MIM in 1966 had the subtitle Catalogs of Autosomal Dominant, Autosomal Recessive and X-linked Phenotypes.1 In the 1994 edition,2 the subtitle became A Catalog of Human Genes and Genetic Disorders—a reflection of the progress in the field since the 1960s.
Nearly all of the 1,486 entries in the first edition of MIM discussed phenotypes. As of January 29, 2007, 6,146 of the >17,300 entries in OMIM represented phenotypes (see table 1 and fig. 3 ); the rest related to genes. Beginning in the late 1960s, entries were created in MIM for individual genes for which no associated Mendelian phenotype was known. The method of interspecific (e.g., mouse-human) somatic cell hybridization made it possible to map genes to specific human chromosomes without the existence of a Mendelizing phenotype that could be used in family linkage studies. The difference between the genomes of the two species in the hybrid substituted for the differences between the genomes inherited from father and mother used in family linkage mapping. Thus, when the thymidine kinase gene (TK1 [MIM *188300]) was mapped to chromosome 17 by study of mouse-human hybrid cell lines,13, 14 an entry was created for the gene, even though no Mendelian variation was known. Already, separate entries had been created for hemoglobin genes such as HBB, the lactate dehydrogenase genes such as LDHA (MIM +150000), and the G6PD gene (MIM +305900), among others. As mapping and cloning of genes advanced, the genes involved were given new entries in MIM, again although no Mendelian variation may have been known. Until the generic autosomal catalog was established (in 1994), autosomal “gene entries” were arbitrarily incorporated in the autosomal dominant catalog.
Figure 3 Growth of MIM and OMIM, in terms of total number of entries.
In the accessioning and curating of gene entries, OMIM works closely with the NCBI reference sequence project and the Human Genome Organisation (HUGO) nomenclature committee. Because each group is involved in curating genes and sequence information, a method for sharing each group’s analyses was established under the direction of Donna Maglott at NCBI. This collaborative effort resulted in the public resource “Locus Link” and its successor “Entrez Gene.” This initiative allows Alan Scott, OMIM’s Deputy Scientific Director for Genes, to review genes in OMIM, to remove duplicates, and to identify “new” genes for consideration of inclusion in OMIM. This is a considerable undertaking, since nearly 23,000 genes with supporting sequence have been identified.