Children’s Mercy Kansas City Expands Sequencing Capabilities

Rare Daily Staff

Children’s Mercy Kansas City is significantly expanding its large-scale whole genome sequencing capacity to accelerate initiatives focused on identifying potential disease causing genetic variants and increase the rate of solving cases of children with undiagnosed rare diseases.

Children’s Mercy Kansas City is adding four Pacific Biosciences’ HiFi sequencing Sequel IIe Systems to its two existing Sequel IIe Systems.

In October 2020, Children’s Mercy and PacBio announced a research collaboration focused on long-read whole genome sequencing of rare disease cases for which previous short-read whole genome and exome sequencing studies yielded no answers. The study, which is currently underway, has already resulted in the detection of multiple new diagnoses, including a novel expansion disorder, precise definition of breakpoints and orientation of structural and copy number variants, and the identification of novel inversions.

Based on the success of that collaborative effort, Children’s Mercy is scaling their sequencing capacity with the goal of completing PacBio HiFi whole genome sequencing for approximately 1,000 exome-negative cases over the next 12 months.

“Thousands of children do not have a clear explanation for what are likely genetic-driven diseases. We are committed to addressing this challenge by refining genomic sequencing to achieve a higher-resolution view of all DNA variation using technologies such as the Sequel IIe System,” said Tomi Pastinen, director of the Center for Pediatric Genomic Medicine at Children’s Mercy. “We expect HiFi whole genome sequencing to help us shorten the diagnostic journey for families not helped by current clinical genome or exome sequencing. Studying the genetics of thousands of children will help us make rapid progress against unknown genetic diseases and lead the way for more children and families in need.”

The PacBio Sequel IIe System generates HiFi sequencing reads, which provide the accuracy and completeness required for investigating DNA variation in rare genetic diseases. Short-read whole genome sequencing can lead to sequence gaps and incomplete coverage of disease-causing gene regions. HiFi whole genome sequencing produces reads approximately 100 times longer than short-read whole genome sequencing, providing high-quality mapping across a genome for comprehensive variant detection.

As part of their collaboration, scientists at Children’s Mercy and PacBio will take advantage of the ability of HiFi sequencing data to reproduce all variants previously detected by short-read whole exome and whole genome methods and to identify novel variants that could explain disease phenotypes.

“At least half of known rare disease cases have not been explained with existing short-read sequencing or other techniques,” said Christian Henry, president and CEO of Pacific Biosciences. “As a result, we are seeing tremendous interest in HiFi sequencing as an important new tool for detecting large or challenging variants missed by short reads.”

The six PacBio Sequel IIe Systems will be installed in the new Children’s Mercy Research Institute building, which was opened on February 18, 2021. The Institute’s new nine-story, 375,000-square-foot building features state-of-the-art laboratories that will support a collaborative approach to research, fostering a partnership among healthcare professionals, researchers, patients, and families.

Tomi Pastinen, director of the Center for Pediatric Genomic Medicine at Children’s Mercy