ClinTAD: a tool for copy number variant interpretation in the context of topologically associated domains.
J Hum Genet
; 64(5): 437-443, 2019 May.
Article
em En
| MEDLINE
| ID: mdl-30765865
ABSTRACT
Standard clinical interpretation of DNA copy number variants (CNVs) identified by cytogenomic microarray involves examining protein-coding genes within the region and comparison to other CNVs. Emerging basic research suggests that CNVs can also exert a pathogenic effect through disruption of DNA structural elements such as topologically associated domains (TADs). To begin to integrate these discoveries with current practice, we developed ClinTAD, a free browser-based tool to assist with interpretation of CNVs in the context of TADs ( www.clintad.com ). We used ClinTAD to examine 209 randomly selected single-nucleotide polymorphism microarray cases with a total of 236 CNVs. We compared 118 CNVs classified as variants of uncertain clinical significance (VUS), where additional insight into pathogenicity of these CNVs would be of greatest utility, to 118 CNVs classified as benign. We found that a higher proportion of VUS had at least two genes in a nearby TAD related to a phenotype seen in the patient based on Human Phenotype Ontology (HPO) annotation. We present example cases demonstrating scenarios where ClinTAD may either increase or decrease clinical suspicion of pathogenicity for VUS, depending on disruption of TAD boundaries and HPO phenotype match. ClinTAD is an easy-to-use tool, based on emerging research in chromatin architecture, that can help inform CNV interpretation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Interface Usuário-Computador
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Análise de Sequência de DNA
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Análise de Sequência com Séries de Oligonucleotídeos
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Polimorfismo de Nucleotídeo Único
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Variações do Número de Cópias de DNA
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Ontologia Genética
Tipo de estudo:
Risk_factors_studies
Limite:
Female
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Humans
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Male
Idioma:
En
Revista:
J Hum Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos