Allele Diagnostics is a CLIA-certified, CAP-accredited clinical genetics testing laboratory that was formed in 2014. Our laboratory focuses on both diagnostic testing and product development. We have developed a novel custom-designed, whole genome chromosomal microarray (CMA) which provides results in as little as 2 days in both prenatal and postnatal settings. The successful design and development of this assay, along with our staff's extensive experience in processing and analyzing CMA tests and building custom CMA analysis software solutions, positions us to develop rapid phenotype-specific CMA tests. Our proposed project is to design and develop a comprehensive CHD (Congenital Heart Defects) gene- centric CMA test, the Rapid Array Diagnosis for CHD or RAD4CHD, that can detect chromosomal aneuploidies and copy number changes at exon level resolution. The test will be intended for patients with CHD diagnosed either prenatally or at birth when a rapid genetic diagnosis is important. The product will address 4 challenges with current genetic testing methodology: 1) need for rapid results, 2) complexity of genetic testing, 3) high cost, 4) limitations in resolution. The assay will increase the diagnostic yield of currently available first-tier testing methods, provide a rapid result in as little as 2 days, reduce testing complexity, and decrease costs. To complete this project, we propose 3 Specific Aims: 1) Design a microarray platform capable of detecting exon level copy number changes of genes and gene regions associated with CHD by completing 2 sub-aims that will provide us with a framework for designing the platform; 2) Assess the performance of the RAD4CHD for speed and quality by analyzing a subset of previously characterized samples to verify that results can be reported out in less than 2 business days from sample receipt; and 3) Verify the RAD4CHD performs equivalently or better than current testing methods regarding genetic aberration testing and time to result. With the data and knowledge acquired from Phase I of our SBIR, we plan to submit a Phase II application, which will consist of validating our product within our laboratory according to American College of Medical Genetics and Genomics (ACMG) guidelines. To complete this, an extensive comparative study will be performed against current genetic testing methods. Once validated, the test will be utilized in a small clinical trial performed at Allele Diagnostics in conjunction with local clinics and hospitals, which currently refer to Allele Diagnostics for genetic testing. Our plan for commercialization will include publishing the results of this study and marketing our product nationally and globally to those physicians who see patients with CHD, including neonatologists, geneticists, cardiologists, maternal-fetal medicine specialists and fetal surgeons.
Public Health Relevance Statement: Allele Diagnostics Phase I SBIR Application
Project narrative: Allele Diagnostics is a CLIA-certified, CAP-accredited clinical genetics testing laboratory that was formed in 2014 to focus on diagnostic testing and product development. Our proposed project is to design and develop a genetic test that can greatly improve cost, turnaround time, and detection rate for genetic causes of congenital heart defects (CHDs) in both prenatal and neonatal settings. CHDs include a wide variety of cardiac lesions and are the most common group of structural birth defects. Rapid diagnosis is important for medical management decisions, such as surgery, to provide adequate education for the families, and to alleviate parental anxiety.
NIH Spending Category: Bioengineering; Biotechnology; Cardiovascular; Congenital Heart Disease; Congenital Structural Anomalies; Genetic Testing; Genetics; Heart Disease; Pediatric; Perinatal Period - Conditions Originating in Perinatal Period; Rare Diseases
Project Terms: Accreditation; Address; Algorithms; Alleles; American; analysis pipeline; Aneuploidy; Anxiety; assay development; Biological Assay; Birth; Businesses; Cardiac; Chromosome abnormality; CLIA certified; Clinical Trials; Clinics and Hospitals; commercialization; Comparative Study; Complex; Computer software; Congenital Heart Defects; cost; Custom; Data; design; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Education; Exons; experience; Family; fetal; Fetus; follow-up; Future; Genes; Genetic; Genetic Diseases; genetic disorder diagnosis; Genetic screening method; genomic aberrations; Genomics; Group Structure; Guidelines; improved; innovation; insertion/deletion mutation; Karyotype; Knowledge; Laboratories; Lesion; Literature; Live Birth; Marketing; Maternal-fetal medicine; Medical; Medical Genetics; medical schools; Methodology; Methods; Microarray Analysis; Neonatal; neonate; novel; Nucleic Acid Regulatory Sequences; Operative Surgical Procedures; Patient Care; Patients; Performance; Phase; Phenotype; Physicians; Positioning Attribute; postnatal; prenatal; Process; product development; Publishing; Quality Control; rapid diagnosis; Reporting; Resolution; Sampling; Severities; Small Business Innovation Research Grant; Specialist; Speed; Structural Congenital Anomalies; Surgeon; Techniques; Testing; Time; tool; Variant; whole genome
