While newborn genetic research holds immense promise for the future of healthcare, its success hinges on advancements in characterizing the genetics of rare diseases.
Today, about a quarter of babies born worldwide undergo some form of newborn sequencing, currently screening from a single to a maximum of 97 conditions for rare conditions. However, current tests cover only a fraction of the ~7,000 genes known to cause disease.
Revvity, Inc., based in Waltham, MA, develops these assays and methods and is at the forefront of utilizing AVITI sequencing in its research endeavors.
Newborn genetic research “delivers on the promise of population genomics, and our goal is to develop more assays to identify more disorders in newborns at an earlier stage," says Dr. Madhuri Hegde, Chief Scientific Officer at Revvity.
The Potential of AVITI Sequencing in Genetic Research
While still in its initial phase, complementing traditional biochemical and molecular assays with next-generation sequencing (NGS) into the research and development of newborn screening routines marks a significant advancement. NGS offers several advantages over traditional research methods including:
- Multiplex testing: NGS allows for the simultaneous examination of multiple disorders, enhancing efficiency and coverage.
- Identifying more genetic markers: researchers can better predict whether early intervention would benefit specific conditions.
- Enhanced disease discovery: NGS can uncover diseases missed by previous methods, such as whole exome sequencing and curated panels.
For instance, research by Revvity published in JAMA Network Open and based on blood samples, found that genome sequencing identified a higher percentage of children at risk for pediatric onset diseases compared to exome-based panels.
This is where AVITI sequencing becomes a pivotal tool, holding great promise for advancing research that could lead to the development of more comprehensive genetic tests for newborns in the future. Revvity is now adopting AVITI in some of its labs around the world, including in the U.S., Sweden and India.
Implementing AVITI in Research Workflows
Revvity has developed an end-to-end workflow incorporating AVITI sequencing to bolster the research and discovery of previously unknown rare diseases. This workflow includes advanced dried blood spot collection and processing devices, nucleic acid extraction kits, liquid handlers, reagents for library preparation, and software for sample quality control.
Dr. Hegde explains the integration of AVITI sequencers: "A comprehensive cross-comparison showed AVITI’s throughput met our research needs perfectly, with improved chemistry reducing duplication rates. This efficiency means fewer reads are discarded, requiring less sequencing overall."
Impact on Genetic Research and Potential Therapies
As access to sequencing grows around the world, it can have a deep impact on global health.
One notable example of the benefit of NGS is in the research of Duchenne muscular dystrophy (DMD). The most common hereditary neuromuscular disease, DMD is caused by mutation of the dystrophin gene, located on chromosome Xp21. Newborn screening for DMD involves an assay for the creatinine kinase enzyme, but research has shown that molecular confirmation is needed to determine if enzyme leakage is due to a defect in the DMD gene. This precise identification is crucial as pharmaceutical companies research potential treatments.
Conclusion
Revvity's use of AVITI exemplifies how cutting-edge sequencing technologies can propel our understanding and management of genetic disorders. As research continues to evolve, the integration of advanced sequencing systems like AVITI promises to unlock new insights, paving the way for more comprehensive and effective newborn screening protocols in the future.
“Newborn screening is probably one of the most successful public health initiatives,” said Dr. Hegde. “Discovering and developing new ways to test will only improve on that record.”