The New York Center for Rare Diseases (NYCRD) at Montefiore, recognized as a Center of Excellence by the National Organization for Rare Disorders (NORD), 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 of, 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 represents the racial and ethnic groups (>90% non-White) 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 NYCRD 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 ascertain if advanced long-read sequencing, a new technology allowing in-depth analysis of the patients’ DNA, can identify complex genetic alterations which remain difficult to detect with current genetic diagnostic tests.

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. 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, D.Med., Ph.D., chief of genomics, and professor of genetics and of pediatrics at Albert Einstein College of Medicine, clinical geneticist at the Children’s Hospital at Montefiore Einstein (CHAM), and co-director of the NYCRD 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.”

“We are thrilled to collaborate with the New York Center for Rare Diseases at Montefiore to empower the underserved communities of the Bronx with the precision that PacBio HiFi sequencing can bring to rare disease research,” said Christian Henry, President and Chief Executive Officer of PacBio. “Our aim is to illuminate rare disease mysteries and bring answers and hope to families navigating the complexities of a rare disease.”

The Division of Genetics at CHAM is one of the oldest and best known in the country. Through partnerships with PacBio, GeneDx and Google, Montefiore’s goal is to offer more lifesaving resources for families with rare diseases and build a foundation for improving care delivered to ethnically and socioeconomically diverse populations in the Bronx and beyond. If a disease is identified because of this project, families will be supported by a geneticist, genetic counselor or social worker at CHAM.

“For more than twenty years, we have pioneered the development of clinical genomic diagnostics, with the goal of ending the diagnostic odyssey for patients with rare genetic diseases,” said Paul Kruszka, M.D., FACMG, Chief Medical Officer at GeneDx. “We are excited to partner with Montefiore, PacBio and Google Health to explore the potential of innovative methods such as long-read sequencing to improve our ability to deliver precise genetic diagnoses.”

Google Health is partnering with the NYCRD 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.

“We’ve seen long reads enable huge advances in making the human reference better reflect human diversity,” said Andrew Carroll, Product lead, Genomics, Google AI. “This project represents the next step – using the comprehensiveness of long reads to find disease-causing variants that have been difficult to discover in under-represented populations. Together with PacBio and Montefiore, we can help improve equity in genomics resources and help end long diagnostic odysseys for patients.”

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About Montefiore Health System

Montefiore Health System is one of New York’s premier academic health systems. It is a recognized leader in providing exceptional quality and personalized, accountable care to approximately three million people in communities across the Bronx, Westchester, and the Hudson Valley. It comprises ten hospitals, including the Children’s Hospital at Montefiore, Burke Rehabilitation Hospital, and over two hundred outpatient ambulatory care sites. The advanced clinical and translational research at its medical school, Albert Einstein College of Medicine, directly informs patient care and improves outcomes. From the Montefiore-Einstein Centers of Excellence in cancer, cardiology and vascular care, pediatrics, and transplantation, to its preeminent school-based health program, Montefiore is a fully integrated healthcare delivery system providing coordinated, comprehensive care to patients and their families. For more information, please visit www.montefiore.org. Follow us on Twitter, Instagram, and LinkedIn, or view us on Facebook and YouTube.