Validation of Optical Genome Mapping for the Identification of Constitutional Genomic Variants in a Postnatal Cohort

NCT ID: NCT05295277

Last Updated: 2023-08-07

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 1000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-11-30
• Study Completion Date: 2024-06-30

Brief Summary

The purpose of this research use only (RUO) study is to detect genomic structural variants (SVs) in human DNA by Optical Genome Mapping (OGM) using the Bionano Genomics Saphyr system. SVs are a type of genetic alternation that includes deletions, duplications, and both balanced and unbalanced rearrangements (ex: inversions or translocations), as well as specific repeat expansions and contractions. The results of OGM analysis will be compared to prior clinical genetic test results to determine how OGM compares to current standard of care (SOC) clinical test methods such as chromosomal microarray analysis (CMA), karyotyping, Southern blot analysis, polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), and/or next generation sequencing (NGS), etc.

Detailed Description

Optical genome mapping (OGM) is an emerging next-generation cytogenomic tool that enables a comprehensive analysis of structural variants (SVs) in the genome. OGM, in its current iteration, is performed on the Saphyr system, which is developed and marketed by Bionano Genomics (San Diego, CA). OGM employs imaging of ultra-long DNA molecules (>150 kbp) that are labeled at a unique 6 base-pair sequence motif (CTTAAG) that occurs throughout the genome. The images of the labeled DNA molecules are used to generate a de novo assembly that can be compared to a reference genome to identify all classes of SVs, such as deletions, duplications, balanced/ unbalanced genomic rearrangements (insertions, inversions, and translocations), and repeat array expansions/contractions). In addition, a separate coverage-based algorithm enables the detection of genome-wide copy number analysis (similar to CMA), and the absence of heterozygosity (AOH) analysis. In the same assay, a concurrent or stepwise data analysis pipeline allows for sizing pathogenic CGG repeat expansions (consistent with fragile X syndrome) as well as D4Z4 repeat contractions which are consistent with facioscapulohumeral muscular dystrophy type 1 (FSHD1). Recently, in several studies, OGM has demonstrated excellent concordance with standard-of-care testing. Importantly, the OGM workflow can provide results within three-five days.

The aim of this double-blinded, multi-site, retrospective, observational, Institutional Review Board (IRB)-approved study is to evaluate the concordance of structural variant detection by OGM compared to standard of care tests (such as CMA, karyotyping, Southern blot analysis, PCR, FISH, and/or NGS, etc.), in a large cohort containing a variety of SVs including aneuploidies, intragenic and contiguous deletions, duplications, balanced and unbalanced translocations, inversions, isochromosomes, ring chromosomes, repeat expansions, repeat contractions, and more. This study is also designed to assess the sensitivity, specificity, and reproducibility of OGM analysis conducted at multiple sites, by numerous operators, and on different Saphyr instruments. Consensus testing and interpretation protocols were developed and implemented at all sites.

Conditions

Developmental Disability; Intellectual Disability; Autism Spectrum Disorder; Congenital Anomaly; Fragile X Syndrome; Facioscapulohumeral Muscular Dystrophy 1

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Standard of care genetic testing group

Individuals with genomic test results from a standard of care (SOC) test (such as CMA, karyotyping, Southern blot analysis, PCR, FISH, and/or NGS, etc.) will be enrolled in the study to compare the SOC result to results from optical genome mapping.

Standard of care genetic testing group

Intervention Type: OTHER

N/A - no intervention as this is an observational study.

Interventions

Standard of care genetic testing group

N/A - no intervention as this is an observational study.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Individual with a genomic aberration identified by CMA, karyotyping, Southern blot analysis, PCR, FISH, and/or NGS or other standard of care (SOC) genetic testing technology whose clinical test results are available to compare with results from OGM.

2. Patients with prior negative SOC genetic testing results whose results are available to compare with results from OGM.

Exclusion Criteria

1. Any individual who opted-out of research at the testing laboratory.

2. An individual whose genetic test contains the following variants: pathogenic sequence variants, abnormalities involving acrocentric p-arms and centromeres, below 20% for mosaicism, and tetraploidy.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Rochester

OTHER

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: collaborator

Greenwood Genetic Center

OTHER

Sponsor Role: collaborator

Praxis Genomics

UNKNOWN

Sponsor Role: collaborator

Augusta University

OTHER

Sponsor Role: collaborator

Medical College of Wisconsin

OTHER

Sponsor Role: collaborator

University of Iowa

OTHER

Sponsor Role: collaborator

Bionano Genomics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alka Chaubey, PhD, FACMG

Role: PRINCIPAL_INVESTIGATOR

Bionano Genomics

Locations

Praxis Genomics

Atlanta, Georgia, United States

Site Status: ACTIVE_NOT_RECRUITING

Augusta University Research Institute

Augusta, Georgia, United States

Site Status: ACTIVE_NOT_RECRUITING

University of Iowa Hospitals & Clinics, Molecular Pathology

Iowa City, Iowa, United States

Site Status: ACTIVE_NOT_RECRUITING

Columbia University Irving Medical Center

New York, New York, United States

Site Status: ACTIVE_NOT_RECRUITING

DNA Microarray CGH Laboratory, Department of Pathology, University of Rochester Medical Center

West Henrietta, New York, United States

Site Status: ACTIVE_NOT_RECRUITING

Greenwood Genetic Center

Greenwood, South Carolina, United States

Site Status: RECRUITING

Lineagen (A Bionano Genomics Company)

Salt Lake City, Utah, United States

Site Status: RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status: ACTIVE_NOT_RECRUITING

Countries

United States

Central Contacts

Alex Hastie, PhD

Role: CONTACT

ahastie@bionanogenomics.com

267-315-0914

Megan Martin, MS

Role: CONTACT

mmartin@bionano.com

801-931-6203

References

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Reference Type: BACKGROUND

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Reference Type: RESULT

Other Identifiers

20203726

Identifier Type: -

Identifier Source: org_study_id