Tomi Pastinen, MD, PhD

Vice President, Associate Chief Medical Officer for Clinical and Research Integration, CMRI; Division Director, Center for Pediatric Genomic Medicine; Dee Lyons/Missouri Endowed Chair in Pediatric Genomic Medicine, Pediatrics/Genomic Medicine Center (GMC); Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Research Professor of Cancer Biology, University of Kansas School of Medicine

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Elin Grundberg, PhD

Roberta D. Harding & William F. Bradley, Jr. Endowed Chair in Genomic Research; Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Research Associate Professor of Pathology, University of Kansas School of Medicine

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Tomi Pastinen, MD, PhD, Vice President, Associate Chief Medical Officer for Clinical and Research Integration, Division Director, Genomic Medicine Center, and Elin Grundberg, PhD, Genomic Medicine Center, received a $3,296,333 R01 federal grant from the National Institutes of Health (NIH)’s Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD). The grant is for their study “Complete human parent-of-origin genome: functional signatures and developmental determinants of disease” for the project period of Aug. 15, 2025 – April 30, 2026 (Award No. 1R01HD117565-01).

The study will fill the gap of the understudied area of imprinting diseases by adding new detailed information on human genome variation. An imprinting disease can occur when a gene behaves differently, and the child only inherits a harmful variant from the mother or father.

During this study, the team will use Children’s Mercy Research Institute’s program, Genomic Answers for Kids (GA4K), long-read 5-base sequencing (5mC-HiFi-GS) data on rare diseases to create an “imprintome” — a comprehensive map of human imprinting genes. An imprinting disease can be identified through DNA methylation, which is included in GA4K’s data.

Pilot examination by the team looked at thousands of rare disease genes from families enrolled in GA4K. During this process, they found DNA methylation signatures with clear parent-of-origin (PofO) patterns, meaning they were able to identify which parent the active gene came from. After detecting gene regions with PofO effects, the team plans to use other sequencing techniques — single-nucleus epigenome analysis and long-read RNA sequencing — to identify functional consequences of gene imprinting at cellular level. The team will also access data from three rare disease cohorts to identify what diseases are caused by disruption in PofO genes.

"The comprehensive understanding of PofO increases accuracy of molecular diagnostics by expanding disease genome and improving the interpretation of phenotypes in known locations," said Drs. Pastinen and Grundberg. "At the same time, studying shared genetic traits and their likely developmental influences can improve how we predict and prevent diseases based on common genetic variations in the population."

Co-investigators are Isabelle Thiffault, MSc, PhD, FACMGG, Assistant Director, Molecular Genetics, Director, Translational Genetics; and Craig Smail, PhD, Genomic Medicine Center.

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