Elin Grundberg, PhD
Roberta D. Harding & William F. Bradley Jr. Endowed Chair in Genomic Research; Associate Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Research Associate Professor of Pathology, University of Kansas School of Medicine
Full BiographyTomi Pastinen, MD, PhD
Dee Lyons/Missouri Endowed Chair in Pediatric Genomic Medicine; Director, Center for Pediatric Genomic Medicine; Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Research Professor of Cancer Biology, University of Kansas School of Medicine
Full Biography
Elin Grundberg, PhD, and Tomi Pastinen, MD, PhD, Genomic Medicine Center, have received a Research Project Grant (R01) from the National Institute of Health’s Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD). The grant is in the amount of $3,333,361 for a project period of July 18, 2024-April 30, 2029 (Project Number 1R01HD115359-01A1).
This latest funding is for the pair’s project titled “5-base HiFi sequencing to advance the understanding of genetic determinants of pregnancy loss,” which looks to see how long-read technologies can fill gaps of genetic variation in families who suffer from recurrent pregnancy loss (RPL). The study will look to help identify the genetic variants or epigenetic biomarkers that cause recurrent pregnancy loss.
“One in every 20 couples suffer from recurrent pregnancy loss where, after current clinical testing including short-read genome-wide sequencing, no reason is found for half of these cases,” explain Drs. Grundberg and Pastinen.
The team will leverage Children’s Mercy’s Genomic Answers for Kids program and the hospital’s clinical and molecular diagnostic data together with access to electronic health records (EHR) and pull pregnancy history to classify molecular variation linked to RPL. They will also use the Children’s Mercy Research Institute’s high- throughput 5-base HiFi-GS platform to consolidate all known molecular tests for genetic disease into a single sequencing run for the identification of presumed variants and complex DNA changes missed by clinical microarray and unmeasured by standard genome sequencing in prospectively enrolled couples suffering from RPL.
Finally, the team will study sperm samples by applying a form of detection that measures DNA methylation levels, which are epigenetic marks that regulate gene expression, through 5-HiFi-GS sequencing. In the samples they will compare levels of father’s DNA changes restricted to germ cells (sperm) and not detected in routine clinical testing from blood. Also, they will look at potential environmental impacts on DNA methylation observable in 5-HiFi-GS from paternal blood and sperm together with fetal DNA.
“The goal is that the information gained can provide a clinical diagnosis and consequently treatment options but also insight into key biological pathways underlying human development,” said Drs. Grundberg and Pastinen. “This could pave the way for new diagnostic evaluation and development of novel treatment strategies.”
Co-investigators on this project include Isabelle Thiffault, PhD, Pathology and Laboratory Medicine, Keith Feldman, PhD, Health Services & Outcomes Research, and Courtney Marsh, MD, Obstetrics & Gynecology, University of Kansas Medical Center.
The contents are those of the investigator and do not necessarily represent the official views of, nor an endorsement, by NIH, or the U.S. Government.