From DNA To Decision

(Posted on Wednesday, February 25, 2026)

Today, it is now possible to read and interpret a complete DNA sequence quickly enough to consistently make timely decisions for newborns or adults. We can obtain whole-genome sequences, but the problem is that each individual has many genetic changes—some inherited, some new. A subset of these changes is well characterized and strongly associated with disease, carrying a high probability of causing serious conditions that warrant timely intervention in infants, children and adults. Many other variants, however, are of ambiguous or unknown significance.

From Newborn Genomes To Real Decisions

Genomic sequencing is rapidly becoming part of routine newborn care, with large programs now able to identify serious genetic conditions days after birth, often before symptoms appear. For conditions like spinal muscular atrophy, where early treatment dramatically alters motor outcomes and survival, the speed of diagnosis can spell the difference between a lifetime of disability and near‑normal development.

New approaches are now being developed to understand, in real time, the potential consequences of specific genetic differences. This is important, particularly when there is a clear marker—a distinct change in a gene with a known biological function. These approaches can help determine whether to initiate appropriate treatment promptly or wait for additional information.

Recent research highlights the promise of functional models that can turn ambiguous genetic findings into actionable information. Using living systems that closely reflect human biology, it’s possible to quickly observe the impact of genetic changes on organs and tissues. This field is still in its infancy, but there has been a recent and important advance in at least one specific case.

In that case, a mutation was found in two infants. The mutation was in critical genes, including SMN1, the gene that causes spinal muscular atrophy when it fails. However, the mutation that was found was one of “unknown signficiance” meaning that it was unclear whether it would lead to the development of spinal muscular atrophy in the children. Therefore, the central question was whether to intervene immediately with existing therapies or to delay action until the risk was better understood.

A Proof Of Concept With High Stakes

To address this, an animal model that provides a rapid functional readout was employed. The zebrafish is a well-established genetic system that leverages decades of work on genome manipulation and gene function in live animals. The human gene carrying the mutation was isolated from the infants and then cloned. It was then inserted into the zebrafish.

Within a short time, they determined that the mutation had no discernible effect on the fish. This was notable because mutations in that same gene, when disease-causing, are known to create a clear, observable impact in the fish. The absence of such an effect indicated that this particular mutation was likely benign.

This real-world demonstration provided the confidence needed to postpone high-risk, high-cost therapies. In this case, both children developed as expected. They did not show signs of muscle weakness or respiratory compromise that would be seen in children with spinal muscular dystrophy. This validates the decision to watch rather than treat. The case showed that it is possible to move quickly from mutations of unknown significance in critical genes to functional understanding to guide rapid clinical decisions, marking the beginning of a new era.

Going Beyond One Disease

The significance of this work goes well beyond spinal muscular atrophy. As gene replacement, gene editing and high‑cost biologics become central tools of regenerative medicine, the field of medicine will encounter an increasing number of rare variants in genes that influence the development, maintenance and repair of tissues throughout the body.

Programs such as the one in Florida, which performs whole-genome sequencing on newborns, are expanding. These efforts generate vast amounts of genomic data but raise the question of how to interpret the numerous variants discovered. While computers can predict some effects and are often useful, computational methods alone often fail—especially when dealing with complex combinations of genes and variants.

For that reason, it’s essential to go beyond purely computational approaches. Functional labs capable of experimentally testing the effects of genetic variants and variant combinations are needed. Building such capabilities is essential to make sound, timely clinical decisions based on genomic data for infants, children and adults.

Functional labs will become a key component of genomic medicine. They will enable us to reliably move from DNA to decision. By combining genomics with rapid tests of variant function, it’s possible to make more confident decisions about when to deploy the most potent tools in the regenerative arsenal and when to let nature take its course without intervention.