MyGene2 Resource Lets Families, Clinicians Searching for Molecular Diagnosis Share Data

ORLANDO, Florida (GenomeWeb) – Researchers at the University of Washington have created a new web-based resource called MyGene2 that lets families and clinicians that have not received a molecular diagnosis from whole-genome or exome sequencing share their information and data, improving their chances to find others with mutations in the same gene. 

At the American Society of Human Genetics meeting in Orlando, Florida today, Jessica Chong, analysis group lead at the UW Center for Mendelian Genomics, presented an overview of MyGene2 and how it has been used so far.

Between 50 percent and 70 percent of patients with a suspected Mendelian disease who undergo genome or exome sequencing remain undiagnosed, she said, though a majority of them have candidate genes identified. If families could share those candidate genes, along with phenotypic data, and find a match, this could lead to additional diagnoses. However, a current bottleneck is the absence of data-sharing opportunities for them.

Families struggling with genetic diseases are already highly motivated to find a diagnosis and take to Facebook and other social media to share their data, Chong said, but MyGene2 is making it easier to do so – not only for families but also for clinicians and researchers.

Families start by adding a profile that includes a free text description of the patient's health data, from which Human Phenotype Oncology (HPO) terms are automatically extracted. They can also add genetic data, including candidate genes, candidate variants, and genetic test reports, as well as VCF variant files for reanalysis.

Everyone who shares data – clinicians and researchers can share de-identified genetic data on behalf of their patients or research participants – can use the resource, and families, clinicians, and researchers have equal access. 

All candidate genes submitted are also available as a list, and for each gene, there is a match report of all families who share this candidate gene. In addition, the resource has information about the variants, such as their inheritance mode and annotations.

Those families who do not yet have any candidate genes because they haven't had exome or genome sequencing can apply for self-paid or free research exome sequencing in a CLIA-certified laboratory, conducted by the UW Center for Mendelian Genomics. Any candidate variants identified in the analysis are immediately shared with the family and MyGene2, and families also obtain a VCF that they can make public for reanalysis.

Currently, MyGene2, which was launched about a year ago, holds cases from 1,225 families submitted by 880 user accounts, which include 723 unique genes, among them many new disease genes. About 70 percent of cases were submitted by clinicians and researchers and about 30 percent by families.

Chong presented a couple of examples where the resource has already been helpful. One family with a girl with seizures and developmental delay opted for self-paid exome sequencing, and within three months was able to post a pathogenic variant identified in the GNB1 gene into the database. GNB1 had been implicated in epilepsy the year before, and the girl was quickly able to enroll in genotype-phenotype studies of GNB1 and connect with another family with the same variant. In addition, the parents were able to identify a potentially actionable secondary finding in the data by their own analysis of the variant data.

In another case, exome sequencing identified KMT2E as a candidate gene, but the family initially could not find someone else with the same mutation. Just this month, two other families joined MyGene2 that also had a result in the KMT2E gene.

Overall, the new database makes it easier for families to share their data in an organized and efficient way, Chong said, and for researchers to recruit families for research projects.

Asked by an audience member whether it might be too much of a burden for families to put it on them to share their data and pursue a diagnosis, Chong said that this is already the case. "It's already on the families. They are being told, 'We did a clinical exome. It's mutation-negative. That's all we've got,'" she said.