Future Challenges of OMIM
As outlined earlier, an objective of OMIM from its beginning as the book MIM has been to catalog the relationship between phene and gene. The organization of MIM/OMIM has evolved to accommodate that fundamental objective of human genetics. Mapping has been important in establishing that relationship and has been comprehensively chronicled in MIM/OMIM. With completion of the sequencing of the human genome, all genes have, in effect, been mapped in terms of their location in the sequence, but many remain to be characterized (“annotated”). The goal now is to relate phenotype to gene function.
Despite the official completion of the human genome project several years ago, the number of identified genes continues to rise, although more slowly. Extrapolating the growth of the number of genes with “known or inferred function” suggests that, barring major surprises (such as the growing number of small RNAs), nearly all genes will belong to this category in the next 6–8 years. Of course, “known” is a relative term; we continue to learn new biology about a great many of the genes already in OMIM. A challenge for OMIM is to capture information describing “new” genes while continuing to add important science to the ∼11,500 current gene entries for which the sequence is known. Other challenges will be to capture alias gene names and to register in some orderly way the complexity of combinatorial alternative splicing and many other surprises that the human genome is likely to reveal.
Mendelian (monogenic or monolocus) phenotypes and their molecular basis will continue to be the principal fodder for the ever enlarging catalogs.82 The mechanism by which the mutation leads to the phenotype (the steps from gene to phene) will always be important information for cataloging. There will be attention also to collation of information on genetic, epigenetic, and environmental modifiers of Mendelian phenotypes. A challenge OMIM already faces is how to catalog complex phenotypes and complex genotypes and their functional relationships to each other and to include epigenetics (and epigenomics), the interaction of genes and gene products, the interaction with and influence of environment, and the emergent phenotypes resulting from these interactions—no small undertaking.
These relationships between complex phenotypes and complex genotypes are under investigation in a large number of clinical and epidemiologic research programs, usually involving, by necessity, large cohorts of subjects, with use of haplotype data for description of the genotype in association studies, and covering a range of topics for study that includes cancer(s), cardiovascular disease(s), asthma, and mental illnesses. OMIM must continue to register this information in a manner that is useful to clinical medicine and that promotes our fundamental understanding of the genetics of health and disease.
Will there ever be another print edition of MIM? At this time, that seems unlikely because of the obvious advantages of the electronic version, with its daily updating and its searchability. The availability of the book in nonelectronic settings and the tables and other appendiceal material in the preface and foreword may not justify its existence. The historian in me regrets the loss of the archival function of the print edition.
My colleague Alan Scott argues that there would be a use for a print version of an annotated human genome atlas with abbreviated MIM entries. He points out that a book is easier to browse, with opportunities for serendipity to operate, than is a computerized database. Such an atlas could be organized chromosome by chromosome with, in effect, a separate “catalog” for each autosome comparable to the present chromosome-specific catalogs (X, Y, and mitochondrial).