ten times more imprinting patterns than any previous study
At Children's Mercy Kansas City, researchers have found a way to read the silent instructions written into human DNA — not the genetic code itself, but the chemical markings that tell cells which parent's voice to listen to. Using HiFi long-read sequencing technology, they uncovered ten times more genomic imprinting patterns than science had previously documented, drawing on samples from early-stage placentas where these instructions are first being written. The discovery matters because when those instructions go wrong, children can suffer from diseases that look genetically normal on the surface — conditions that have long resisted explanation. This is science learning, at last, to read between the lines.
- Rare pediatric diseases have long confounded doctors precisely because the DNA sequence looks correct — the error lies not in the code but in how it is being read, a distinction that standard sequencing tools were never built to catch.
- HiFi long-read sequencing changes the game by reading longer, unbroken stretches of DNA, making the chemical marks that silence one parent's gene visible for the first time at scale.
- Testing more than 200 samples from placentas at six to eight weeks — the precise developmental window when imprinting patterns are established — researchers identified ten times more imprinting signatures than any prior study had found.
- Each newly mapped pattern is a potential answer to a child's unexplained growth failure, developmental delay, or metabolic disorder — turning what was once a diagnostic dead end into a navigable map.
- Presented at the Pediatric Academic Societies meeting in Honolulu, the findings are already drawing clinical attention, with researchers anticipating that wider adoption of the technology will continue expanding the catalog of known imprinting patterns.
A research team at Children's Mercy Kansas City has made a discovery that could rewrite how medicine understands rare childhood diseases — not by finding errors in the genetic code itself, but by revealing flaws in the instructions that govern how that code is read. The phenomenon at the center of their work is called genomic imprinting, a process by which a child's cells use only one parent's copy of certain genes, chemically silencing the other. When this system misfires, the results can include growth disorders, developmental delays, and metabolic conditions that have long puzzled clinicians because the underlying DNA sequence appears entirely normal.
Led by Elin Grundberg at the Genomic Medicine Center, the team applied HiFi long-read sequencing to more than 200 genetic samples from early-stage placentas — tissue drawn from nearly seventy pregnancies at six to eight weeks of development, the critical window when imprinting patterns are first being established. Unlike older methods that fragment DNA and attempt to reassemble it, HiFi sequencing reads longer, continuous stretches, making it possible to see the chemical markers that indicate which parent's gene is active and which is silenced. The result: ten times more imprinting patterns identified than any previous study had documented.
The implications reach far beyond the laboratory. Each newly identified pattern represents a potential explanation for a disease that may have gone undiagnosed for years — a child with unexplained symptoms, a family without answers. Researchers now have a far more complete map of where the imprinting process can go wrong, and clinicians have new tools for turning genetic detective work into something more systematic. Presented at the Pediatric Academic Societies meeting in Honolulu, the findings signal that as HiFi sequencing becomes more widely available, the catalog of known imprinting patterns will keep growing — and with it, the possibility of better diagnosis, clearer understanding, and, eventually, better treatment for some of childhood's most elusive diseases.
A team of researchers at Children's Mercy Kansas City has developed a way to read human DNA with unprecedented clarity, and what they found suggests that science has been missing crucial clues about why some children are born with rare genetic diseases. The discovery centers on a phenomenon called genomic imprinting—a quirk of inheritance where a child's body uses only one parent's copy of a particular gene, silencing the other. When this process goes wrong, it can trigger disorders that have puzzled doctors for years. Now, using a technology called HiFi long-read sequencing, researchers have identified ten times more imprinting patterns than any previous study had documented.
The research team, led by Elin Grundberg at the Genomic Medicine Center, tested their approach on more than two hundred genetic samples extracted from early-stage placentas—tissue from nearly seventy pregnancies at six to eight weeks of development. This is the critical window when genomic imprinting patterns are being established in a developing fetus. What made HiFi sequencing different from older methods was its ability to read longer stretches of DNA without breaking them into fragments, which meant researchers could see the full context of how genes were being marked and expressed. The patterns that emerged revealed imprinting signatures that standard sequencing had simply missed.
Genomic imprinting is not a flaw in the genetic code itself—the DNA sequence is normal. Rather, it is a chemical marking system that tells cells which version of a gene to use. Think of it as a set of instructions that says "use mom's copy of this gene, ignore dad's" or vice versa. This selective expression is normal and necessary for healthy development. But when the imprinting process misfires, when the wrong parent's gene gets silenced or the right one fails to be marked, children can develop conditions ranging from growth disorders to developmental delays to metabolic problems. Many of these diseases have been difficult to diagnose because the genetic code looks correct—the problem lies in how that code is being read.
The significance of finding ten times more imprinting patterns than previously known is not merely academic. Each newly identified pattern represents a potential explanation for a disease that may have gone undiagnosed or misdiagnosed. A child presenting with unexplained growth failure or developmental regression might now have a genetic answer. Parents seeking to understand why their child is different from other children might finally have clarity. And researchers working to develop treatments now have a much more complete map of where things can go wrong.
HiFi long-read sequencing works by allowing researchers to sequence much longer pieces of DNA in a single read, rather than breaking DNA into small fragments and trying to reassemble them like a puzzle. This longer view makes it possible to see the chemical marks—methyl groups attached to DNA—that indicate which genes are imprinted. The technology also helps researchers determine which parent's gene is being silenced, a critical piece of information for understanding inheritance patterns and predicting risk in future pregnancies.
The research was presented at the Pediatric Academic Societies meeting in Honolulu in late April, where it drew attention from clinicians and researchers focused on rare childhood diseases. The work suggests that as this technology becomes more widely available and more placentas and tissue samples are analyzed, the catalog of known imprinting patterns will continue to expand. That expansion could transform how doctors approach children with mysterious symptoms, turning genetic detective work into something more systematic and more successful. For families living with rare genetic diseases, the implications are profound: better diagnosis, better understanding, and potentially better treatment.
Citas Notables
New technologies continue to enhance understanding of rare diseases. HiFi long-read sequencing helps researchers uncover insights into human development and potentially identify diseases that have eluded science.— Elin Grundberg, PhD, Genomic Medicine Center, Children's Mercy Kansas City
La Conversación del Hearth Otra perspectiva de la historia
Why does it matter that they looked at placentas specifically, at that six-to-eight-week window?
That's when the imprinting marks are being laid down. It's like catching the process in the act. If you look at a child's cells years later, the marks are already set. But in the placenta at that early stage, you can see which genes are being marked and how, before anything goes wrong or right.
And this HiFi technology—what was the old way missing?
Length. Older sequencing breaks DNA into tiny pieces and tries to reassemble them. When you're looking for chemical marks on DNA, you need context. You need to see a longer stretch to understand the pattern. HiFi reads longer stretches in one go, so the marks are visible in their full context.
So they found ten times more patterns. Does that mean ten times more diseases?
Not necessarily. It means ten times more places where imprinting happens. Some of those patterns might not cause disease. But each one is a place where something could go wrong, and now researchers know to look there.
For a parent whose child has symptoms no one can explain, what does this change?
It gives doctors a much larger map to search. If a child has growth problems or developmental delays and genetic testing has come back normal, imprinting disorders were often missed because no one was looking for them in the right way. Now there's a better way to look.
Is this technology available to clinicians now, or is it still research-only?
It's still primarily in research settings, but that's changing. As the technology becomes cheaper and more hospitals adopt it, it will move into clinical practice. The research being presented now is building the knowledge base that clinicians will need to use it effectively.