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

NCT05295277 | Unknown

• 1 other identifier: 20203726
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 8

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.

Conditions

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

Keywords

Validation study; Comparison study; New technology compared to standard of care

Outcome Measures

Primary Outcomes (1)

• Sensitivity/Concordance and specificity of OGM with standard of care testing for detection of structural variants.

  OGM results are evaluated against the standard of care test and concordance (sensitivity and specificity) will be determined.

  Through study completion, an average of 1 year

Secondary Outcomes (1)

• Reproducibility and identification of structural variants beyond the limit of detection of standard of care methods.

  Through study completion, an average of 1 year

Study Arms (1)

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.

Other: Standard of care genetic testing group

Interventions

Standard of care genetic testing group OTHER

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

Standard of care genetic testing group

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals will be recruited if they have standard of care genetic test results (such as CMA, karyotyping, Southern blot analysis, PCR, FISH, and/or NGS, etc.) to compare to optical genome mapping results.

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Bionano Genomics: lead
• University of Rochester: collaborator
• Columbia University: collaborator
• Greenwood Genetic Center: collaborator
• Praxis Genomics: collaborator
• Augusta University: collaborator
• Medical College of Wisconsin: collaborator
• University of Iowa: collaborator

Study Sites (8)

Praxis Genomics

Atlanta, Georgia, 30328, United States

ACTIVE NOT RECRUITING

Augusta University Research Institute

Augusta, Georgia, 30912, United States

ACTIVE NOT RECRUITING

University of Iowa Hospitals & Clinics, Molecular Pathology

Iowa City, Iowa, 52242, United States

ACTIVE NOT RECRUITING

Columbia University Irving Medical Center

New York, New York, 10032, United States

ACTIVE NOT RECRUITING

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

West Henrietta, New York, 14586, United States

ACTIVE NOT RECRUITING

Greenwood Genetic Center

Greenwood, South Carolina, 29646, United States

RECRUITING

Lineagen (A Bionano Genomics Company)

Salt Lake City, Utah, 84109, United States

RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

ACTIVE NOT RECRUITING

Related Publications (8)

• Shieh JT, Penon-Portmann M, Wong KHY, Levy-Sakin M, Verghese M, Slavotinek A, Gallagher RC, Mendelsohn BA, Tenney J, Beleford D, Perry H, Chow SK, Sharo AG, Brenner SE, Qi Z, Yu J, Klein OD, Martin D, Kwok PY, Boffelli D. Application of full-genome analysis to diagnose rare monogenic disorders. NPJ Genom Med. 2021 Sep 23;6(1):77. doi: 10.1038/s41525-021-00241-5.

  PMID: 34556655 BACKGROUND

• Stence AA, Thomason JG, Pruessner JA, Sompallae RR, Snow AN, Ma D, Moore SA, Bossler AD. Validation of Optical Genome Mapping for the Molecular Diagnosis of Facioscapulohumeral Muscular Dystrophy. J Mol Diagn. 2021 Nov;23(11):1506-1514. doi: 10.1016/j.jmoldx.2021.07.021. Epub 2021 Aug 9.

  PMID: 34384893 BACKGROUND

• Mantere T, Neveling K, Pebrel-Richard C, Benoist M, van der Zande G, Kater-Baats E, Baatout I, van Beek R, Yammine T, Oorsprong M, Hsoumi F, Olde-Weghuis D, Majdali W, Vermeulen S, Pauper M, Lebbar A, Stevens-Kroef M, Sanlaville D, Dupont JM, Smeets D, Hoischen A, Schluth-Bolard C, El Khattabi L. Optical genome mapping enables constitutional chromosomal aberration detection. Am J Hum Genet. 2021 Aug 5;108(8):1409-1422. doi: 10.1016/j.ajhg.2021.05.012. Epub 2021 Jul 7.

  PMID: 34237280 BACKGROUND

• Chaisson MJP, Sanders AD, Zhao X, Malhotra A, Porubsky D, Rausch T, Gardner EJ, Rodriguez OL, Guo L, Collins RL, Fan X, Wen J, Handsaker RE, Fairley S, Kronenberg ZN, Kong X, Hormozdiari F, Lee D, Wenger AM, Hastie AR, Antaki D, Anantharaman T, Audano PA, Brand H, Cantsilieris S, Cao H, Cerveira E, Chen C, Chen X, Chin CS, Chong Z, Chuang NT, Lambert CC, Church DM, Clarke L, Farrell A, Flores J, Galeev T, Gorkin DU, Gujral M, Guryev V, Heaton WH, Korlach J, Kumar S, Kwon JY, Lam ET, Lee JE, Lee J, Lee WP, Lee SP, Li S, Marks P, Viaud-Martinez K, Meiers S, Munson KM, Navarro FCP, Nelson BJ, Nodzak C, Noor A, Kyriazopoulou-Panagiotopoulou S, Pang AWC, Qiu Y, Rosanio G, Ryan M, Stutz A, Spierings DCJ, Ward A, Welch AE, Xiao M, Xu W, Zhang C, Zhu Q, Zheng-Bradley X, Lowy E, Yakneen S, McCarroll S, Jun G, Ding L, Koh CL, Ren B, Flicek P, Chen K, Gerstein MB, Kwok PY, Lansdorp PM, Marth GT, Sebat J, Shi X, Bashir A, Ye K, Devine SE, Talkowski ME, Mills RE, Marschall T, Korbel JO, Eichler EE, Lee C. Multi-platform discovery of haplotype-resolved structural variation in human genomes. Nat Commun. 2019 Apr 16;10(1):1784. doi: 10.1038/s41467-018-08148-z.

  PMID: 30992455 BACKGROUND

• Chan S, Lam E, Saghbini M, Bocklandt S, Hastie A, Cao H, Holmlin E, Borodkin M. Structural Variation Detection and Analysis Using Bionano Optical Mapping. Methods Mol Biol. 2018;1833:193-203. doi: 10.1007/978-1-4939-8666-8_16.

  PMID: 30039375 BACKGROUND

• Barseghyan H, Tang W, Wang RT, Almalvez M, Segura E, Bramble MS, Lipson A, Douine ED, Lee H, Delot EC, Nelson SF, Vilain E. Next-generation mapping: a novel approach for detection of pathogenic structural variants with a potential utility in clinical diagnosis. Genome Med. 2017 Oct 25;9(1):90. doi: 10.1186/s13073-017-0479-0.

  PMID: 29070057 BACKGROUND

• Lam ET, Hastie A, Lin C, Ehrlich D, Das SK, Austin MD, Deshpande P, Cao H, Nagarajan N, Xiao M, Kwok PY. Genome mapping on nanochannel arrays for structural variation analysis and sequence assembly. Nat Biotechnol. 2012 Aug;30(8):771-6. doi: 10.1038/nbt.2303.

  PMID: 22797562 BACKGROUND

• Iqbal MA, Broeckel U, Levy B, Sinner S, Sahajpal N, Rodriguez V, Stence A, Awayda K, Scharer G, Skinner C, Stevenson R, Bossler A, Nagy PL, Kohle R. Multi-site technical performance and concordance of optical genome mapping: constitutional postnatal study for SV, CNV, and repeat array analysis. MedRxiv (pre-print). 2021 Dec 30; doi: https://doi.org/10.1101/2021.12.27.21268432

  RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood or banked lymphoblastoid cell lines (LCLs) will be sent to Bionano Genomics for sample blinding. Specimens are aliquoted, banked, and stored frozen. The specimens will be used for OGM testing or follow up testing using standard of care test methods, as needed and determined by the study protocol.

MeSH Terms

Conditions

Developmental Disabilities; Intellectual Disability; Autism Spectrum Disorder; Congenital Abnormalities; Fragile X Syndrome

Condition Hierarchy (Ancestors)

Neurodevelopmental Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Child Development Disorders, Pervasive; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; X-Linked Intellectual Disability; Sex Chromosome Disorders; Chromosome Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Heredodegenerative Disorders, Nervous System

Study Officials

• Alka Chaubey, PhD, FACMG

  Bionano Genomics

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alex Hastie, PhD

CONTACT

267-315-0914; ahastie@bionanogenomics.com

Megan Martin, MS

CONTACT

801-931-6203; mmartin@bionano.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2022
• First Posted: March 25, 2022
• Study Start: November 30, 2020
• Primary Completion: March 31, 2024
• Study Completion: June 30, 2024
• Last Updated: August 7, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)