Design, optimization and validation of a diagnostic panel comprised of ABCA4 pathogenic variants causing Stargardt disease in the Newfoundland and Labrador population

Rajabi, Hoda (2016) Design, optimization and validation of a diagnostic panel comprised of ABCA4 pathogenic variants causing Stargardt disease in the Newfoundland and Labrador population. Masters thesis, Memorial University of Newfoundland.

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Abstract

The objective of this translational research project was to develop, optimize and validate a diagnostic panel of the 20 pathogenic variants in the ABCA4 gene previously identified to cause Stargardt disease in the population of Newfoundland and Labrador (NL). Two different laboratory developed test (LDT) panels (1x20-plex & 2x20-plex) were designed and genotyping was performed on the Sequenom MassARRAY 4 system using genomic DNA from both Stargardt patients and population controls. A set of minimum criteria was established to accurately determine genotyping calls; 1x20-plex LDT panel was selected based on quality metrics. Assessment of the validation cohort including 78 previously tested genomic DNA samples, blind to the investigator, resulted in establishing analytical sensitivity (100%), specificity (100%), accuracy (100%), and reproducibility (100%). A total of 1039 control samples were assessed using the 1x20-plex LDT panel and the minor allele frequencies of 0% - 0.76% for NL, and 0% - 0.60% for non-NL samples were determined.

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