Whole Genome Sequencing Solution Targets Unsolved Rare Disease Cases

Rare diseases often present persistent diagnostic challenges for patients and families. Many patients undergo years of testing without receiving a diagnosis, and even comprehensive genetic testing can miss or fail to interpret disease-causing changes. A newly launched test solution now combines whole genome sequencing, RNA analysis, and ongoing reanalysis to support rare disease diagnosis.

Ambry Genetics (Aliso Viejo, CA, USA) has launched GenomeNext and GenomeReveal, a comprehensive whole genome sequencing (WGS) solution designed to help improve diagnosis of patients with rare diseases. GenomeNext analyzes a patient’s genome using a pangenome reference designed to better represent human genetic diversity. The approach is intended to improve variant detection across diverse ancestral backgrounds.

GenomeReveal adds integrated RNA analysis, which can provide additional evidence to help interpret certain DNA findings. The testing also includes Ambry’s Patient for Life program, through which laboratory-initiated proactive reanalysis re-evaluates patient data as gene-disease knowledge evolves. This reanalysis is designed to deliver clinically meaningful reclassifications to patients who previously received negative or uncertain results.

Published data cited by Ambry show that RNA analysis can significantly increase diagnostic yield. The cited research includes a 2024 JAMA Oncology study on diagnostic outcomes of concurrent DNA and RNA sequencing in individuals undergoing hereditary cancer testing. Ambry also cited a 2025 Genetics in Medicine study reporting that laboratory-driven proactive reanalysis led to positive reclassifications in 5% of initially negative or uncertain exome sequencing cases.

“Advances in the use of a pangenome reference representing wider human diversity, like RNA analysis, and ongoing reanalysis are not just technical upgrades. They lead to a more complete approach to clinical genomics that enables better variant detection, improves diagnostic yield across diverse populations and provides clinically meaningful insights that evolve over time. This is where the field is heading, toward more comprehensive, equitable and lifelong care for patients,” said Dr. Wendy Chung, Chief of the Department of Pediatrics at Boston Children’s Hospital and Mary Ellen Avery Professor of Pediatrics, Harvard Medical School.

Related Links:
Ambry Genetics