Genome-wide association studies using genotyping microarrays have long been a critical tool in understanding how genetic variation impacts disease. The problem is, most of these studies are based on genetic markers from people of European descent predominately, with little global diversity. Underrepresentation of diverse populations in genomic analysis hinders the ability to fully understand disease cause and correlation, and perpetuates inequality in patient care.
South San Francisco, CA-based Twist Bioscience is working with the Regeneron Genetics Center (RGC) in Tarrytown, NY, for the production of a custom next-generation sequencing (NGS) population genetics genotyping assay. Arising from a need to incorporate the genetic differences of global populations, this assay is designed to gain new insights into disease mechanisms, identify new drug targets, and accelerate drug discovery and development. Twist will market the assay as the Twist Diversity SNP Panel, and will make the content available to researchers globally for their population genomics studies.
According to the company, the Twist Diversity SNP panel is inclusive of roughly 1.4 million globally-representative genetic variations known as single-nucleotide polymorphisms (SNPs).
“Leveraging Twist’s custom NGS panel design capabilities, the RGC developed a first-of-its-kind, proprietary population genotyping assay that includes DNA probes that capture globally diverse genetic sequence variations,” said John Overton, PhD, vice president and chief sequencing officer at RGC. “This targeted panel integrates into our existing fully automated exome processing workflow, and provides base calls and imputed variants whose quality already exceeds the array-based approaches we were using. We began using this panel in late 2020 in the RGC and already we are seeing positive results in our integrated research to better understand the biology of human diseases.”
SNP microarray has been the gold standard of genetic study, said Twist Biosceince CEO and Co-Founder Emily Leproust, PhD. However, Leproust said Twist has noticed an increasing number of customers asking for a complete genotyping solution that allows flexibility for customized disease research, and she said Twist believes this is the future of disease marker testing.
“Collaborating with Regeneron to optimize the assay with content from multiple ethnicities enables increased characterization of diverse populations to improve understanding around disease, and potentially therapeutic development as well. We’re pleased to bring the Twist Diversity SNP assay to the scientific community.”
The Diversity SNP assay also enables research centers to consolidate their data generation costs and physical footprints by leveraging next-generation sequencers for both genotyping and exome/custom panels rather than maintaining separate genotyping instrumentation and lab space. While microarrays provide information about the presence or absence of a genetic variant, the Diversity SNP panel produces dynamic, multi-faceted information across a broad spectrum of the population. In addition, the panel can be iterated quickly to build a customized assay incorporating real-time journal and database entries, Twist noted.
As the first release in Twist’s emerging targeted genotyping-by-sequencing portfolio, the Twist Diversity SNP panel leverages the company's DNA synthesis platform to generate a global panel of more than 600,000 probes governing about 1.4 million SNPs. Used separately as a stand-alone genotyping panel or as an addition (spike-in) into Twist’s Human Comprehensive Exome panel, the company said this assay gives researchers a new ethnicity-neutral gold standard to use in generating genotyping data to match with their sequencing and other genomic data.