By Michael Goodman
July 6, 2016 | The introduction of exome and whole-genome sequencing in 2010 has accelerated the discovery of genes underlying Mendelian disorders. However delineating new Mendelian conditions by comparing phenotypic traits across families is still challenging, especially with limited sharing of health and genetic data among researchers.
The Origins of MyGene2
MyGene2 has its genesis with a patient named Milo. Milo is a young child who presented with developmental delays, hypotonia, and distinctive facial characteristics. A few years ago, his parents established a website and took to social media to identify other families with a child harboring similar clinical symptoms. They quickly made contact with another family who led them to a publication that reported a variant of unknown significance (VUS) in the KDM1A gene in a child with similar symptoms. That made three families.
Milo’s parents reached out to the Center for Mendelian Genomics (CMG) at the University of Washington (one of four NIH-supported centers working to identify the genomic causes of Mendelian diseases) to help delineate the condition, confirm that the variants in KDM1A were causal, and report the findings to the community of researchers.
Michael Bamshad, professor of Pediatrics and principal investigator at CMG took away some lessons from this experience, in particular: the power of social media as a way to connect families with Mendelian conditions and to set in motion the process of gene discovery.
This March, Bamshad and Jessica Chong, an instructor in Pediatrics, launched MyGene2—a play on “My Genes Too” to symbolize the family’s role—as a platform for connecting families with Mendelian conditions with other families and with researchers and clinicians. “If a family is interested in making a diagnosis, there was no single place that served as a repository for useful information, that organized it in a way that made matching possible, and facilitated making the information available to clinicians and researchers. MyGene2does all those things,” says Bamshad.
The Need That MyGene2 Addresses
Other sites focused on developing and disseminating discoveries in Mendelian genetics had arisen over the past decade. Matchmaker Exchange is one such site, and MyGene2 will soon be a part of its network.
But Bamshad says most others were developed primarily for researchers and clinicians. Typically, a researcher enters the name of a gene, and if another researcher enters the same gene, there’s a match. But Bamshad says the problem is that there are a lot of false positives because the information being shared is often incomplete, usually including the gene name but not phenotypic information about the inheritance pattern. Other times, information is withheld by researchers intent on preserving their authorship rights and “ownership” over the patient’s information.
MyGene2 is focusing on linking families with similar genotypes with other families, clinicians, and researchers. Sequencing is often done for a family that has a child with a rare genetic condition, but physicians can’t always make a definitive diagnosis based solely on the identification of a candidate gene from exome sequence data. And, HIPPA regulations preclude them from sharing identifiable health-related data.
Now, clinicians with a candidate gene who are trying to determine whether it’s causal can create a de-identified family profile on MyGene2 that includes both phenotypic information and candidate genes and scan the profiles entered by other clinicians and families.
“What we’re trying to do” Bamshad says, “is to empower families by engaging them as citizen scientists.” Families can create their own profiles, adding the details they’ve discovered about genetic information (is the gene known or unknown?), detailed family history, descriptions of symptoms, photos—anything that will facilitate making a match.
MyGene2 doesn’t monitor exchanges between users once a match is made. It facilitates the match, but once a family has been matched with another family or with a researcher, further communication takes place outside of MyGene2.
This points to another unique aspect of MyGene2: all information is warehoused and shared equally with all users, and matches will eventually be automated and reported out rapidly. Getting clinicians and researchers motivated to use such a public system will require a cultural change. Some of the barriers that will need to be overcome include making sure that credit for a discovery is attributed correctly, academic institutions recognize alternative pathways of “publishing,” and funding agencies acknowledge the merits of rapid dissemination of knowledge.
Scientists are currently sitting on hundreds of discoveries, but Bamshad says the way scientists have worked for years on gene discovery—i.e., getting a single grant to do it, “owning” the data, working on it for years—“those days are coming to an end.”
There are upwards of 7,000 Mendelian conditions, genes have been discovered for about half of them, and industry has translated that knowledge into treatments for fewer than 200 rare diseases. MyGene2, as a first step in this process, is trying to make gene discovery more rapid and efficient.