Interpretation of copy number alterations identified through clinical microarray-comparative genomic hybridization

摘要

Array-comparative genomic hybridization (array-CGH) has become the first-tier technology for the clinical assessment of copy number alterations (CNAs) associated with features such as developmental delay, congenital malformations, autism, or dysmorphic features. It is a near certainty that at least 1 CNA will be identified in each array-CGH assay and the challenge then becomes differentiating between benign CNA and those copy number changes that are dosage sensitive and relate to the abnormal phenotype in question. With advances In array-CGH platform coverage, it is no longer a question of CNA identification, but rather of CNA interpretation. However, there is no single methodology employed by laboratories to conduct this process, and unfortunately all too often the end results provide no clear answer to the ordering physician or their patients. Recent approaches for interpretation of CNA have advanced to suggesting the use of first-generation computational models based on structural and functional genomic features to predict a pathologic or benign value for array-CGH findings. Although such estimation procedures can be helpful, they are currently limited to a single phenotype (mental retardation) and can at best only provide an educated guess as to the true clinical significance of these alterations.