The growing importance of carrier screening in genomics

Carrier screening is one of the most influential ways genetics is shaping the future of human health. By revealing inherited risks before they ever appear, carrier screening has changed how we think about reproductive health, population genetics, and research into rare conditions. Over the years a handful of targeted tests for specific populations has grown into large panels that can examine hundreds of genes at once.

Carrier screening is all about enabling healthier families, informing clinical decision-making, and strengthening research into the architecture of human disease. Millions of people carry genetic variants that have no effect on their own health but may matter for their children. Carrier screening brings those possibilities into focus, informing how we plan, study, and prepare for the future.

Carrier screening identifies whether someone is a carrier – a typically healthy individual who has a single copy of a gene linked to a genetic condition but remains unaffected because the other copy functions normally. For most autosomal recessive conditions affected by a single gene, both parents must carry a variant in the same gene for a child to be at risk. In this case, there is

• a 25% chance the child will inherit both altered copies and develop the condition,

• a 50% chance the child will also be a healthy carrier, and

• a 25% chance the child will inherit two normal copies.

However, these odds differ for conditions linked to the X chromosome . Males always inherit their Y chromosome from their father, and their X chromosome from one of their mother’s two copies. If a mother is a carrier of an X-linked recessive disease, her son will have a 50% chance of developing the disease and her daughter will have a 50% change of being a carrier.

This distinction is what makes carrier screening so impactful – by helping to forecast the possibilities that may arise in the next generation. This knowledge is foundational for population health research at large.

Historically, carrier screening was limited to specific conditions or populations , such as ancestry-based screening for Tay-Sach’s disease in Ashkenazi Jewish communities. With the rapid progression of molecular screening techniques, this narrow approach has broadened to what is now considered expanded carrier screening (ECS).

Instead of focusing on a few genes only, ECS examines hundreds of genes simultaneously and its impact has been notable. Studies show that expanded carrier screening can detect more risks than a targeted approach and highlight just how common it is to be a carrier , reinforcing the idea that these risks are not unusual, but rather a normal part of human genetics.

Carrier screening methods have progressed as technology has advanced. The earliest tools were biochemical assays that measured enzyme activity to detect specific diseases like Tay-Sach’s. These assays were effective but could only be applied to a small number of conditions.

Targeted genotyping panels expanded the scope slightly, allowing multiple known variants to be tested at once. Panels became standard for conditions like cystic fibrosis but were still restricted to variants that had already been identified.

The introduction of next-generation sequencing (NGS) however, enabled a step change for carrier screening. NGS made it possible to sequence dozens or hundreds of genes simultaneously, enabling expanded carrier screening panels. However, even with the shift to NGS, many significant hurdles have remained. Regions of the genome like repeat expansions, structural variants, and genes with pseudogenes or methylation signatures remain stubbornly difficult to analyze for many existing NGS technologies.

Which leads us to a broader truth: carrier screening is only as good as the methods behind it. By improving accuracy and expanding the types of variants detected, new approaches promise to make screening more powerful and more reliable.

Looking ahead, carrier screening will continue to expand in scope, accuracy, and impact. These trends are shaping the future of this field:

By capturing more conditions, carrier panels have the potential to reduce the burden of inherited disease on a population scale and make carrier screening more accessible. Making this possible will require continued investment in diverse variant databases and offering screening more broadly across populations to deliver its full public health impact.

Improved accuracy of carrier panels provides higher confidence in its results. To fully understand and characterize challenging genes, highly accurate long-read sequencing technologies, like HiFi, are needed achieve a comprehensive view of disease-causing genetic variants, particularly in historically challenging genes containing epigenetic modification, repeat expansions, large structural variants, copy number variants, and high-homology genes.

Current carrier screening workflows often require multiple legacy assays to fully characterize certain genes. For example, labs commonly run older and less accurate genotyping methods like Southern blots, MLPA (multiplex ligation-dependent prob amplification), PCR-based methods, or capillary electrophoresis and Sanger sequencing for genes that are not accurately characterized by short reads. These layered workflows can add time, cost, and complexity.

To learn more about how HiFi sequencing is being used in a comprehensive Thalassemia assay on the HBA and HBB loci as well as other complex loci like FMR1 , SMN1 , and CYP21A2 read our customer success story and interview with Dr. Aiping Mao from Berry Genomics

As announced earlier this year , the roadmap to expand PureTarget panels resolves many of these obstacles to achieve scalable, high accuracy carrier screening research. The new PureTarget carrier panel is purpose-built to tackle a group of 12 difficult-to-genotype genes that are commonly analyzed with these legacy techniques, consolidating these tests into one high-resolution, high-throughput solution. This panel will serve as a powerful frontline assay that can be run in parallel with routine short-read panels, ensuring comprehensive detection of complex variants that may otherwise go unnoticed or require expensive follow up analysis.

To learn more about how PacBio is working toward this future, visit our genetic testing page and learn more about PureTarget .