New DNA technology could help identify rare pediatric diseases

Key takeaways:

• Researchers identified new sites in the placenta where genomic imprinting occurs.
• This could find previously overlooked genes that are associated with rare pediatric diseases.

HONOLULU — Researchers have identified thousands of new sites in the placenta where genomic imprinting occurs, which they said could help identify genes that are associated with rare disorders.

They described how the long-read genome-sequencing technology works at the Pediatric Academic Societies Meeting.

The technology, called 5-base long-read HiFi genome sequencing, can read DNA molecules that are 100 times longer than normal sequencing technologies, which makes it more accurate at identifying which genes are inherited from mothers vs. fathers, according to Elin Grundberg, PhD, researcher and professor of pediatrics in the Genomic Medicine Center at Children’s Mercy Kansas City. She said it can also read epigenetic signatures — a type of modification of DNA — which helps researchers interpret genetic variation.

Grundberg and Tomi Pastinen, MD, PhD, vice president and associate chief medical officer for clinical research and integration at Children’s Mercy, tested the technology on more than 200 samples from mothers, fathers, as well as placenta between 6 and 8 weeks’ gestation. They were specifically looking for instances of genomic imprinting, which occurs when a child inherits only one working copy of a gene from one parent and not the other.

“Genomic imprinting is a phenomenon that, if dysregulated, can cause congenital disease such as Angelman syndrome or Prader-Willi syndrome,” Grundberg told Healio.

The researchers discovered 10 times more instances of genomic imprinting than found in previously published data, according to a press release. Specifically, they identified thousands of new sites where imprinting occurred, and the vast majority of these sites were where the mother’s copy of the gene was silenced. For the sites where the father’s copy appeared silenced, they could use sperm samples to validate that silencing occurs before fertilization. Less than 30% of sites maintained effect at later developmental stages, which means genomic imprinting was mostly restricted to the placenta, the researchers wrote.

“Our findings point toward thousands of novel genomic imprinting regions,” Grundberg said. “Consequently, our findings may help diagnose new pediatric rare diseases.”

Grundberg said the next step in this research will incorporate gene variants from families who have a child with a suspected rare disease that has not been diagnosed yet.

“Incorporating our new map of genomic imprinting signatures may thus result in previously overlooked genes turning out to be diagnostic,” she said.

For more information:

Elin Grundberg, PhD, wishes to be contacted through newsroom@cmh.edu.

References:

• Grundberg E, et al. Mapping parent of origin methylation by long-read sequencing reveals novel imprinting and insight into pediatric disease. Presented at: Pediatric Academic Societies Meeting; April 24-28, 2025; Honolulu.
• New DNA-reading technology holds promise for rare disease research. https://www.eurekalert.org/news-releases/1081696. Published April 25, 2025. Accessed April 26, 2025.