International Standards for Cytogenomic Arrays
The International Standards for Cytogenomic Arrays (ISCA) Consortium is a rapidly growing group of clinical cytogenetics and molecular genetics laboratories committed to improving quality of patient care related to clinical genetic testing using new molecular cytogenetic technologies including array comparative genomic hybridization (aCGH) and quantitative SNP analysis by microarrays or bead chip technology. The ISCA Consortium is now working with the sequencing community to extend the goals of standardization, collaboration, and data sharing. To reflect this combined effort, we are becoming ICCG, or the International Collaboration for Clinical Genomics.
Efforts of the Consortium include:
Clinical Utility: The ISCA Consortium has made recommendations regarding the appropriate clinical indications for cytogenetic array testing (Miller et al. AJHG 2010, PMID: 20466091). Currently, discussions are focused on pediatric applications for children with unexplained developmental delay, intellectual disability, autism and other developmental disabilities. A separate committee has been developed to address appropriate cancer genetic applications (http://www.urmc.rochester.edu/ccmc/).
Evidence-based standards for cytogenomic array design: The Consortium will develop recommendations for standards for the design, resolution and content of cytogenomic arrays using an evidence-based process and an international panel of experts in clinical genetics, clinical laboratory genetics (cytogenetics and molecular genetics), genomics and bioinformatics. This design is intended to be platform and vendor-neutral (common denominator is genome sequence coordinates), and is a dynamic process with input from the broader genetics community and evidence-based review by the expert panel (a Steering Committee with international representation).
Public Database for clinical and research community: It is essential that a publicly available database be created and maintained for cytogenetic array data generated in clinical testing laboratories. This will be integrated into the current dbGaP database at NCBI/NIH and released through dbVar, and curated by a committee of clinical genetics laboratory experts. The very high quality of copy number data (i.e., deletions and duplications) coming from clinical laboratories combined with expert curation will produce an invaluable resource to the clinical and research communities.
Standards for interpretation of cytogenetic array results: Using the ISCA Database, along with other genomic and genetics databases, the Consortium will develop recommendations for the interpretation and reporting of pathogenic vs. benign copy number changes as well as imbalances of uncertain clinical significance.
Membership in the ISCA Consortium is open to all individuals and laboratories involved in cytogenetic array testing who are committed to free data sharing and to participation in a process to develop evidence-based standards and guidelines to improve patient care.
ISCA is available through dbVar:
http://www.ncbi.nlm.nih.gov/dbvar/studies/nstd37/
http://www.ncbi.nlm.nih.gov/dbvar/studies/nstd75/
http://www.ncbi.nlm.nih.gov/dbvar/studies/nstd45/
http://www.ncbi.nlm.nih.gov/dbvar/studies/nstd101/
- Type: Clinical Genetic Testing
- Archiver: The database of Genotypes and Phenotypes (dbGaP)