Detection of Chromosomal Aberrations in Clinical Practice: From Karyotype to Genome Sequence

Abstract

Since the inception of clinical cytogenetics in the late 1950s, the field has witnessed the evolution of multiple methodologies for the evaluation of chromosomal imbalances and rearrangements. From the replacement of solidly stained chromosomes by Giemsa banding (G-banding) to in situ hybridization and microarrays, each technique has sought to detect smaller and smaller chromosomal aberrations across the genome. Microarray analysis has revealed that copy-number variants—a class of mutation resulting from the loss (deletion) or gain (duplication) of genomic material that is >1 kb in size—are among the significant contributors to human disease and normal variation. Here, we evaluate the history and utility of various methodologies and their impact on the current practice of clinical cytogenetics.