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OMIM Turns 50: A Genetic Database’s Past, Present, and Future

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OMIM Turns 50: A Genetic Database’s Past, Present, and Future

Victor McKusick with residents atop Administration Building dome.

Credit:Johns Hopkins Medicine

OMIM Turns 50: A Genetic Database’s Past, Present, and Future

By Christy Brownlee 

May 2017—When Online Mendelian Inheritance in Man (OMIM) was first published in 1966, its catalog of human genes, genetic disorders and traits looked a little different than it does now. For starters, it would be more than two decades later until OMIM was actually online. Second, from the catalog’s inception, the data were stored on magnetic tape, an early form of computerized data storage—and in all caps, due to limitations in the technology. Third, for many years, MIM—as it was known at the time, before it was online—had very few genes listed because the technology didn’t exist yet to find them. Instead, this catalog initially consisted of 1,487 descriptions written by OMIM’s creator, Victor A. McKusick, known as the father of modern genetic medicine. 

Victor Mckusick Victor Mckusick

From these humble beginnings, OMIM is now a collection of more than 24,000 entries, most of them focused on genes rather than phenotypes, and accessed thousands of times every day by clinicians, researchers and others around the world. This year, OMIM turns 50—an incredible milestone for a resource that will continue to have an impact on the field of genetics far into the future. 

“You really can’t do human genetics work without it,” says OMIM scientific director Ada Hamosh, M.D., the Dr. Frank V. Sutland Professor of Pediatric Genetics and member of Johns Hopkins’ McKusick-Nathans Institute of Genetic Medicine. “I don’t say that because I run it, but because I’m a geneticist, and I and tens of thousands of scientists, clinicians and others use it all the time.”

Looking Back

OMIM was just one of the legacies left behind by McKusick, whose career at Johns Hopkins spanned from the time he began medical school there in 1942 until his death in 2008. After training as a cardiologist, McKusick became interested in genetic syndromes, such as Peutz-Jeghers and Marfan syndromes. Eventually, his interest spread to other inherited disorders such as those found in Amish communities. 

In 1957, he founded the Division of Medical Genetics at the Johns Hopkins School of Medicine. Soon afterwards, McKusick got the idea for MIM. 

Early on, McKusick was the sole author of MIM.  He was assisted in compiling the information for the catalogs by Medical Genetics fellows from the Moore Clinic.  From 1966 to 1986, the book was published every three to four years. As the field expanded and researchers discovered more and more about genetic diseases, the book started publishing every two years.  McKusick brought on colleagues and dedicated MIM employees to assist in development of the knowledge base.  Among the first was Carol Bocchini, now editorial director of OMIM, who with McKusick laid the foundation of content and structure that is OMIM today. 

In the 1980s, McKusick worked with the National Library of Medicine to use MIM as a test bed for natural language search software.  With the help of Nina Matheson at the Welch Medical Library, McKusick and his colleagues provided the first online and completely searchable version of MIM in 1987. “OMIM was ‘online’ before online even existed,” quips Hamosh. The knowledge base was now updated nightly, and researchers from around the world began accessing OMIM daily. And in 1995, MIM was adapted for the World Wide Web. 

OMIM family treeCharting the family tree of the Mendelian Inheritance in Man (view full sized version). Credit: Hopkins Medicine Magazine

Joanna Amberger, OMIM’s program manager, started working with McKusick as a research assistant a year after OMIM transitioned to the online format. Back then, Amberger maintained and developed MIM’s gene map and morbid map, work she still continues today.  “It’s hard to imagine in today’s world, where so much information is at your fingertips, how eye-opening it was to suddenly be able to search across a catalog of information like MIM so easily,” Amberger says.

Tool for the Clinic and Lab

Today, between 60,000 and 90,000 unique users access OMIM every month, hailing from every country that has Internet access, says Hamosh. Some users, like David Valle, M.D., professor of pediatrics at the Johns Hopkins University School of Medicine and director of the McKusick-Nathans Institute of Genetic Medicine, are on OMIM multiple times a day to get the information they need to serve patients. 

OMIM has evolved from a catalog of genetic phenotypes into a compendium of entries on genes, phenotypes or both, with virtually everything else that’s known about them: clinical features of phenotypes, their molecular basis, the crystal structure of proteins produced from genes, animal models of those genes or phenotypes.  In addition, has many links to external resources, making it easy to access DNA or protein sequence, molecular pathway and variant databases, gene-testing registries, clinical trial databases and more.

Valle says that OMIM has helped him solve a tricky diagnosis or determine a patient’s clinical needs far more times than he can count. For example, the day before he was interviewed for this article, Valle accessed OMIM to help a pediatric patient who has hearing loss and other characteristics of a rare genetic disorder called Usher syndrome, which is the leading cause of deaf-blindness. Although this patient didn’t have evidence of vision problems, it was possible that he had a late-onset form of the disease.

Using OMIM, Valle says, he was able to gather information about different types of Usher syndrome, a disease that few medical geneticists will see in their lifetimes—knowledge that helped him counsel the young patient’s parents and that will eventually steer targeted genetic testing.

Valle has also used OMIM as a research tool. Several years ago, he and his lab, along with colleagues at Harvard and Notre Dame, used OMIM to gather a collection of phenotypic features that overlapped among different diseases to see if genes connected to these conditions might also overlap. This initial “diseasome” was published in PNAS in 2007, leading to dozens of offshoot research studies since.

“Every day, OMIM has increased value as a hub for information for the clinical and research geneticist alike,” Valle says.

Growing into the Future

Currently, a dedicated staff of 14 full- and part-time employees compile the vast amount of information in OMIM that’s updated daily, curating it from the hundreds of journals that publish information relevant to this resource. As OMIM heads into its next 50 years and the field continues to grow, Valle says, new technology may be necessary to keep up with the constant influx of information. For example, rather than having science writers read and decide on whether information on genes or phenotypes is worth including, a computerized text reader might eventually be able to lessen the load.

The type of information included in OMIM is also undergoing a slow shift, says OMIM’s deputy director of genes Alan Scott, Ph.D., associate professor of medicine at the Johns Hopkins University School of Medicine and member of the McKusick-Nathans Institute for Genetic Medicine. McKusick invited Scott, who runs the Genetic Resources Core Facility at Johns Hopkins, to join OMIM in 1995 to sort out overlaps in descriptions of genes produced by different research groups that ultimately proved to be the same genes.

At the time, only protein-coding genes were thought to influence phenotypes. Since then, a multitude of non-protein-coding genes have been discovered to influence phenotypes through their actions on protein-coding genes. Some of these are currently described in OMIM, but Scott and other experts suggest that this number is only the tip of the iceberg when it comes to the real total. Eventually, he says, OMIM will incorporate these genes, too, adding yet another layer to the rich body of information that’s grown over the last half-century.

“In 50 years, we’ll probably have a much more detailed description of essentially every base in the genome and have a much better understanding of what they do,” he says. “It’s not exactly clear to me right now how OMIM will capture this data, but I’m quite certain that it will.”