Overview
This sequencing project will help enable earlier detection of rare diseases in newborns to improve patient outcomes and reduce health care costs associated with rare disease diagnosis.
Newborn screening (NBS) is a public health program that identifies treatable rare diseases (RDs) at birth. Newborn Screening Ontario performs NBS for Ontario, Newfoundland, part of Quebec and Qikiqtaaluk (~150,000/yr). Most of the current 31 NBS RDs are identified via metabolomics. However, the emergence of transformative therapies for non-metabolic RDs has created an urgent need for DNA screening methods. Pilot programs worldwide are assessing whole genome sequencing (WGS) in NBS, termed genomic NBS (gNBS), and Canada is behind. gNBS will revolutionize precision health by enabling early detection of an expanding array of treatable RDs, optimizing patient outcomes and reducing health care costs. Our current NBS program identifies ~0.5% of infants requiring RD treatment; with gNBS, based on comparable studies, we would triple the number of infants detected and treated for RDs. We will collaborate with gNBS pilots in England, Australia and the US, building on their success, to establish a Canadian gNBS pilot. Activity 1: Establish a panel of RDs for testing. gNBS requires targeted WGS analysis for target RDs. Consulting with gNBS collaborators and the Canadian RD community (medical experts and patients/families), we will define a set of RDs appropriate for Canadian gNBS. Deliverable: Panel of RDs to be used in gNBS (Q2/Y1) Activity 2: WGS of 9,000 infants born in Ontario, Quebec, Newfoundland and Qikiqtaaluk. We will recruit 9,000 infants from the general population through social-media and advertisements targeting designed to capture the diversity of the Canadian population. Participants will undergo short read WGS with analysis of our gNBS panel using residual dried blood spots (DBS) collected for routine NBS. Their clinical phenotypes, metadata, and metabolomic data will be provided to the Pan Canadian Genome Library (PCGL). Two subsets of patients will have additional testing and data for PCGL: ~500 will be screened for Type 1 diabetes risk through the CanScreenT1D Project, and 1,000 will undergo untargeted metabolomic analysis. Together, our unselected cohort has broad geographic and ancestral diversity, overcoming the biases in studies with targeted cohorts. Milestones: 400 samples (Y1), 2,900 samples/yr (Y2-3), 2,800 samples (Y4) Deliverable: WGS and associated data for ~9,000 infants from the general population Activity 3: Confirm the sensitivity of NBS by gNGS. NSO identifies ~1,000 screen positive infants annually. To confirm the sensitivity of gNBS for routine NBS disorders, we will recruit these infants. All data will be deposited at PCGL along with clinical data on their RD. Milestones: 100 samples(Y1), 300 samples/yr (Y2-4) Deliverable: WGS from 1,000 infants with NBS disorders. Evaluation of gNBS sensitivity for current NBS conditions Our study will pilot an equitable program to ensure that Canadian infants benefit from the precision health initiative, laying the groundwork for the much-anticipated future of NBS.