As many as 7 in 10 people carry at least one pathogenic genetic variant, even if they have no family history of disease1. That means most couples could unknowingly pass on an inherited condition to their children, underscoring the urgency for comprehensive carrier screening research programs.

What was once a niche practice limited to specific conditions or populations, carrier screening has now become a regular part of reproductive health conversations for everyone. To have the most impact, these conversations should be based on the most updated information regarding potential risks associated with certain inherited diseases, and research into populations and communities that may be most impacted. Having this information available can provide families a chance to better understand their potential for being affected by these conditions and help them make more informed plans.

Guidelines from organizations like the American College of Obstetricians and Gynecologists (ACOG) and the American College of Medical Genetics and Genomics (ACMG) reflect this reality, calling for broader and more inclusive approaches to screening2,3. Yet meeting those expectations has been difficult, because the genes most critical to reproductive health are often the most difficult to sequence. This, in turn, makes research on these genes challenging, preventing the useful dissemination of information to potentially impacted populations.

This week PacBio released the expanded PureTarget portfolio with a set of new kits available now that bring HiFi long-read sequencing to carrier screening research at scale and represent a major step forward in modernizing how labs approach inherited disease. With PureTarget, laboratories can replace legacy methods such as triplet-primed PCR, MLPA, and PCR and Sanger sequencing with one comprehensive workflow.

 

Carrier screening meets HiFi sequencing

A handful of genes have consistently caused the biggest challenges in carrier screening, including FMR1 for fragile X syndrome, SMN1 for spinal muscular atrophy, and HBA1/2 for Alpha thalassemia. Each presents unique challenges like long tandem repeat expansions, GC-rich sequences, near-identical pseudogenes, or complex structural variation that short-read sequencing alone cannot reliably resolve.

Traditionally, this pushed labs back onto older assays. Repeat-primed PCR was used to size expansions, MLPA to detect copy number changes, and long-range PCR to characterize structural variation. These tools did the job, but they belong to an earlier era of genetics. They were often labor-intensive, fragmented, and ultimately limited in scalability.

PureTarget powered by HiFi long-read sequencing offers a modern alternative. With read lengths that span kilobases and accuracy greater than 99.9 percent, HiFi sequencing can directly capture the regions that once required separate technologies. Instead of supplementing sequencing panels with piecemeal methods, labs can now get everything they need from a comprehensive long-read panel for 96 samples in a single sequencing run.

PureTarget packages HiFi sequencing into panels specifically designed for carrier screening research, making legacy add-on assays unnecessary and enabling comprehensive, high-throughput workflows.

 

Long-read sequencing for comprehensive carrier screening

The expanded PureTarget portfolio includes three distinct panels.

The carrier screening panel covers inherited conditions, including all ACMG tier 3 genes2 that are considered technically challenging. The repeat expansion panel provides high-resolution analysis of neurological disease–associated tandem repeat expansions. The control panel supports custom assay design and validation for labs tailoring their assays to specific populations or research priorities.

Available in 24- and 96-sample formats, the kits were designed to fit the needs of both focused research programs and large-scale initiatives. A single Revio system can support throughput of up to 100,000 PureTarget samples per year, allowing labs to maintain the high-volume workflows they already run while replacing outdated, multi-assay approaches with a unified modern solution.

For researchers, this creates cleaner, more consistent datasets that reflect the capabilities of modern sequencing rather than the limitations of older methods. This consolidation offers the promise of results that arrive faster and with fewer caveats.

 

How HiFi sequencing delivers confidence for carrier screening

Accuracy is what makes a result reliable. Legacy methods often introduced uncertainty: repeat-primed PCR could size repeats but fell short for non-canonical repeat motifs, and MLPA could measure copy number but not identify sequence changes. By contrast, HiFi sequencing allows PureTarget to:

Resolve repeat expansions such as those in FMR1 directly, without PCR or Southern blots. Determine full haplotype and copy number of nearly identical genes, such as SMN1 and SMN2, without relying on MLPA. Detect large deletions or inversion in a single workflow rather than through multiple separate tests.

As Dale Muzzey, Chief Scientific Officer of Myriad Genetics, observed:

 

“PureTarget is a breakthrough because it focuses PacBio’s outstanding long-read sequencing quality on clinically relevant, hard-to-sequence regions across many samples at once. This approach not only streamlines lab workflows by reducing the need for multiple specialized assays, but it can also enhance both the sensitivity and specificity of results.”

 
The value here is clear. By eliminating older, piecemeal technologies, PureTarget improves output while simplifying delivery.

 

Carrier screening at population scale

Carrier screening is no longer a niche practice for select groups. It is increasingly a public health priority, with health systems and governments exploring national initiatives4. For example, researchers at Berry Genomics have pioneered the use of HiFi sequencing in China for widescale, PCR amplicon-based assays for single-gene disorders including thalassemia5, congenital adrenal hyperplasia6, spinal muscular atrophy7.

While these examples highlight important advances, the path to truly comprehensive programs at large has been constrained by the inefficiency of legacy assays. PureTarget provides an exciting streamlined approach by consolidating 12 genes into one long-read sequencing workflow. This can enable population-scale programs with wide-ranging implications.

With this adoption, research benefits too, with large-scale studies now able to rely on sequencing that reflects today’s standards instead of being held back by yesterday’s limitations.

 

Future-ready panels

For years, delivering comprehensive carrier screening has meant layering multiple technologies on top of one another, adding cost and complexity at every step. Each legacy assay comes with its own validation requirements, service contracts, instruments, and technician certifications. Training staff across multiple workflows is costly, and keeping older equipment online drains budgets long after its value has peaked.

The expanded PureTarget portfolio makes those extra layers unnecessary. By consolidating carrier screening into a single HiFi sequencing workflow, labs can retire outdated assays, reduce the number of service agreements they maintain, and focus staff expertise on one modern platform. That means lower costs, simpler operations, and a sustainable way to keep pace as standards expand. With modular content, automation support, and customizable control panels, PureTarget provides a future-proof framework that adapts to tomorrow’s needs.

 

Moving carrier screening beyond legacy workflows

The story of carrier screening until now has been one of complexity: a patchwork of short reads combined with repeat-primed PCR, MLPA, PCR, Sanger sequencing and more, all stitched together. The expanded PureTarget panels change that story.

Legacy assays give way to modern HiFi sequencing. Inconclusive results give way to confident answers. Fragmented workflows give way to unified clarity.

For labs, this means sustainable programs built on a modern foundation. It means receiving answers rooted in the best of today’s technology rather than yesterday’s.

 

The future of carrier screening is here

With the expanded PureTarget portfolio, PacBio is replacing outdated, fragmented technologies with the reliability and scalability of HiFi sequencing, bringing clarity and confidence to carrier screening at scale. By delivering clearer results, this innovation can influence the health outcomes of generations to come.

The future of carrier screening is available now.

 

References

Guo, D., et al. (2025). Regional patterns of genetic variants in expanded carrier screening: a next-generation sequencing pilot study in Fujian Province, China. Frontiers in Genetics, 16, 1527228. Guha, S., et al. & ACMG Laboratory Quality Assurance Committee. (2024). Laboratory testing for preconception/prenatal carrier screening: A technical standard of the American College of Medical Genetics and Genomics (ACMG). Genetics in Medicine, 26(7), 101137. Gregg, A. R., et al. & ACMG Professional Practice and Guidelines Committee. (2021). Screening for autosomal recessive and X-linked conditions during pregnancy and preconception: a practice resource of the American College of Medical Genetics and Genomics (ACMG). Genetics in Medicine, 23(10), 1793-1806. Kraft, S. A., Duenas, D., Wilfond, B. S., & Goddard, K. A. (2019). The evolving landscape of expanded carrier screening: challenges and opportunities. Genetics in Medicine, 21(4), 790-797. Liang, Q., et al. (2021). A more universal approach to comprehensive analysis of thalassemia alleles (CATSA). The Journal of Molecular Diagnostics, 23(9), 1195-1204. Liu, Y., Chen, M., Liu, J., et al. (2022). Comprehensive analysis of congenital adrenal hyperplasia using long-read sequencing. Clinical chemistry, 68(7), 927-939. Li, S., Han, X., Zhang, L., et al. (2023). An effective and universal long-read sequencing-based approach for SMN1 2+ 0 carrier screening through family trio analysis. Clinical chemistry, 69(11), 1295-1306.