New York Rare Disease Center Enters Partnership to Increase Genomic Testing of Underrepresented Populations in the Bronx

Rare Daily Staff

The New York Center for Rare Diseases at Montefiore is partnering with GeneDx, PacBio, and Google Health to deliver genetic diagnoses for Bronx families living with rare diseases.

The goal of the new partnership is to help identify the genetic causes and best treatments for rare diseases that have remained undiagnosed, despite using today’s most advanced tests.

On average, the search for a rare disease diagnosis takes five to seven years and can be fraught with misdiagnoses. In some cases, it can take more than a decade. The focus of this research project on the Bronx in New York City adds a level of complexity to rare disease diagnostics. The population in the Bronx is more than 90 percent non-white and represents the racial and ethnic groups that have historically been underrepresented in genomic research, leading to higher rates of inconclusive findings in genomic testing. With almost a third of Bronx residents living below the poverty line, the borough represents communities for whom access to advanced genomic diagnostics is typically limited.

The New York Center for Rare Diseases pilot project involves advanced genomic testing on 50 trios—patients with undiagnosed suspected rare diseases and their two biological parents, 150 people in total, to determine if advanced long-read sequencing can identify complex genetic alterations which remain difficult to detect with current genetic diagnostic tests. Long-read sequencing is a new technology allowing in-depth analysis of the DNA of these patients.

For comparison, standard-of-care testing will be performed at the GeneDx lab, located in Gaithersburg, Maryland, using short-read whole genome sequencing, the most advanced test used in clinical practice today. The same blood sample will be used by GeneDx for research genetic testing, performing PacBio HiFi long-read DNA and RNA sequencing. The genomic data will be returned to the secure computing environment at Albert Einstein College of Medicine, where the collaborative team will implement novel analyses to find the cause of the patient’s symptoms.

Google Health is partnering with the center to develop analytical tools, using Google’s DeepVariant and DeepConsensus tools, designed to identify the genetic cause of a rare disease using advanced sequencing technologies in individuals of diverse origins.

The goal is to use these new long-read sequencing technologies to identify DNA or RNA sequence changes causing genetic diseases, overcoming gaps in today’s standard, whole genome short-read sequencing.

“To date, genetic sequencing has mostly been conducted on people from European ancestry, neglecting the racial and ethnic groups that represent the majority of our Bronx patients,” said John Greally, co-director of the New York Center for Rare Diseases at Montefiore. “By performing these new, advanced genomic sequencing studies on Bronx patients who have given permission for their DNA to be used in research, we will deliver answers to these families, learn how best to perform genomic studies and optimize the care for people impacted by these rare diseases.”

Photo: John Greally, co-director of the New York Center for Rare Diseases at Montefiore