Novel strategies for enhanced analysis of repeat disorders

SummaryThe goal of this project is to establish feasibility for diagnostic sequencing of clinically relevant short tandem repeatSTRDNA markers on therd generation MinION nanoporeNPsequencing platformusing tailored STR specific reagents and analytical softwareThis new and innovative modality has the potential to create a paradigm shift in clinical research and diagnostics of repeat disorderas it can ultimately bring the analysis of recalcitrant STR DNA elements up to par with current genetic NGS assay standardsOur approach leverages the platform s unique longand direct read capabilities for STR applications and comprehensively addresses current NP platform limitations and STR specific challenges through innovative wetware and interpretive softwareSuccessful implementation of Oxford Nanopore s sequencing technology for STR analysis will allow high resolution and comprehensive long range genotypingimprove sampleand gene multiplexing capabilitiesstreamline genetic testing workflows and reduce turn around timewhile markedly shrinking laboratory capital costs and instrumentation footprint to a andlt$pocket sized deviceProof of principle for STR sequencing will be pursued for the Fragile X associated CGG repeat region in the FMRgene in the context of a much needed high throughput and comprehensive Fragile X carrier screening application that will provide FMRallele specific sizing and AGG analysis acrosssamples in a single reaction and less thanhours to resultsFragile X carrier screening is supported by professional testing guidelines and routinely performedtherefore a single assay that can provide streamlined allele specific CGG repeat length and AGG interruption profiles is positioned to benefit hundreds of thousands of individuals per year Project NarrativeThe long term goal of this project is to develop and commercialize a novel size sequencing assay for clinically relevant short tandem repeatSTRDNA markersThis approach will be broadly applicable in the diagnosis of multiple neurological disordersincluding fragile X syndromeamyotrophic lateral sclerosisALSAlzheimer s diseaseand myotonic dystrophyInitiallywe will focus on applying this technology to the analysis of the clinically important Fragile X associated FMRgeneand the technology will provide a number of benefits over current methods by enhancing analysis resolutionincreasing testing throughputreducing turn around time for results and eliminating the need for costly and cumbersome laboratory equipment