Dataset Information

Phenotypic information in genomic variant databases enhances clinical care and research: the International Standards for Cytogenomic Arrays Consortium experience.

ABSTRACT: Whole-genome analysis, now including whole-genome sequencing, is moving rapidly into the clinical setting, leading to detection of human variation on a broader scale than ever before. Interpreting this information will depend on the availability of thorough and accurate phenotype information, and the ability to curate, store, and access data on genotype-phenotype relationships. This idea has already been demonstrated within the context of chromosomal microarray (CMA) testing. The International Standards for Cytogenomic Arrays (ISCA) Consortium promotes standardization of variant interpretation for this technology through its initiatives, including the formation of a publicly available database housing clinical CMA data. Recognizing that phenotypic data are essential for the interpretation of genomic variants, the ISCA Consortium has developed tools to facilitate the collection of these data and its deposition in a standardized structured format within the ISCA Consortium database. This rich source of phenotypic data can also be used within broader applications such as developing phenotypic profiles of emerging genomic disorders, identification of candidate regions for particular phenotypes, or creation of tools for use in clinical practice. We summarize the ISCA experience as a model for ongoing efforts incorporating phenotype data with genotype data to improve the quality of research and clinical care in human genetics.

SUBMITTER: Riggs ER

PROVIDER: S-EPMC3327820 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Phenotypic information in genomic variant databases enhances clinical care and research: the International Standards for Cytogenomic Arrays Consortium experience.

Riggs Erin Rooney ER Jackson Laird L Miller David T DT Van Vooren Steven S

Human mutation 20120320 5

Whole-genome analysis, now including whole-genome sequencing, is moving rapidly into the clinical setting, leading to detection of human variation on a broader scale than ever before. Interpreting this information will depend on the availability of thorough and accurate phenotype information, and the ability to curate, store, and access data on genotype-phenotype relationships. This idea has already been demonstrated within the context of chromosomal microarray (CMA) testing. The International S ...[more]

PMID: 22331816

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Project description: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. 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: <a href="http://www.ncbi.nlm.nih.gov/pubmed/20466091" target="_blank">20466091</a>). 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 (<a href="http://www.urmc.rochester.edu/ccmc/" target="_blank">http://www.urmc.rochester.edu/ccmc/</a>). 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: <a href="http://www.ncbi.nlm.nih.gov/dbvar/studies/nstd37" target="_blank">http://www.ncbi.nlm.nih.gov/dbvar/studies/nstd37/</a> <a href="http://www.ncbi.nlm.nih.gov/dbvar/studies/nstd45" target="_blank">http://www.ncbi.nlm.nih.gov/dbvar/studies/nstd45/</a>

Project description: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: <a href="http://www.ncbi.nlm.nih.gov/pubmed/20466091" target="_blank">20466091</a>). 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 (<a href="http://www.urmc.rochester.edu/ccmc/" target="_blank">http://www.urmc.rochester.edu/ccmc/</a>). 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: <a href="http://www.ncbi.nlm.nih.gov/dbvar/studies/nstd37/" target="_blank">http://www.ncbi.nlm.nih.gov/dbvar/studies/nstd37/</a> <a href="http://www.ncbi.nlm.nih.gov/dbvar/studies/nstd75/" target="_blank">http://www.ncbi.nlm.nih.gov/dbvar/studies/nstd75/</a> <a href="http://www.ncbi.nlm.nih.gov/dbvar/studies/nstd45/" target="_blank">http://www.ncbi.nlm.nih.gov/dbvar/studies/nstd45/</a> <a href="http://www.ncbi.nlm.nih.gov/dbvar/studies/nstd101/" target="_blank">http://www.ncbi.nlm.nih.gov/dbvar/studies/nstd101/</a>

Project description:The use of Cannabis is gaining greater social acceptance for its beneficial medicinal and recreational uses. With this acceptance has come new opportunities for crop management, selective breeding, and the potential for targeted genetic manipulation. However, as an agricultural product Cannabis lags far behind other domesticated plants in knowledge of the genes and genetic variation that influence plant traits of interest such as growth form and chemical composition. Despite this lack of information, there are substantial publicly available resources that document phenotypic traits believed to be associated with particular Cannabis varieties. Such databases could be a valuable resource for developing a greater understanding of genes underlying phenotypic variation if combined with appropriate genetic information. To test this potential, we collated phenotypic data from information available through multiple online databases. We then produced a Cannabis SNP database from 845 strains to examine genome wide associations in conjunction with our assembled phenotypic traits. Our goal was not to locate Cannabis-specific genetic variation that correlates with phenotypic variation as such, but rather to examine the potential utility of these databases more broadly for future, explicit genome wide association studies (GWAS), either in stand-alone analyses or to complement other types of data. For this reason, we examined a very broad array of phenotypic traits. In total, we performed 201 distinct association tests using web-derived phenotype data appended to 290 uniquely named Cannabis strains. Our results indicated that chemical phenotypes, such as tetrahydrocannabinol (THC) and cannabidiol (CBD) content, may have sufficiently high-quality information available through web-based sources to allow for genetic association inferences. In many cases, variation in chemical traits correlated with genetic variation in or near biologically reasonable candidate genes, including several not previously implicated in Cannabis chemical variation. As with chemical phenotypes, we found that publicly available data on growth traits such as height, area of growth, and floral yield may be precise enough for use in future association studies. In contrast, phenotypic information for subjective traits such as taste, physiological affect, neurological affect, and medicinal use appeared less reliable. These results are consistent with the high degree of subjectivity for such trait data found on internet databases, and suggest that future work on these important but less easily quantifiable characteristics of Cannabis may require dedicated, controlled phenotyping.

Dataset Information

Phenotypic information in genomic variant databases enhances clinical care and research: the International Standards for Cytogenomic Arrays Consortium experience.

Publications

Phenotypic information in genomic variant databases enhances clinical care and research: the International Standards for Cytogenomic Arrays Consortium experience.

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