Detecting Copy Number Variants and Runs of Homozygosity on a Single Array — Challenges and Applications

In constitutional genetics research, analysis of single nucleotide polymorphisms (SNPs) provides invaluable insight into a number of conditions. When analysed in conjunction with copy number variation (CNV) data from array comparative genomic hybridisation (aCGH) arrays, this insight can aid in the identification of additional genetic variants to those yielded by the CNV data alone. Protocols for high-resolution SNP arrays can be time consuming whereas aCGH array protocols are less laborious, and as the gold-standard for CNV detection, well established in laboratory workflows. Recent advances have made it possible to combine CNV probes with probes able to detect SNPs on a single aCGH+SNP array, affording the benefits of shorter processing time and dual data with easy integration into the workflow. Although these combined arrays do not have the resolution capabilities of traditional SNP platforms, they have been research-validated to provide informative SNP data for various genetic aberrations such as uniparental disomy (UDP), mosaic aneuploidy and runs of homozygosity (ROH), without compromising on high quality CNV data. Researchers commonly report biologically relevant SNP data at lower resolutions and indeed the argument exists that increased resolution does not necessarily equal an increase in informative data. This application note explores the various applications of combined arrays, the challenges faced in their implementation and their many advantages such as the easy to interpret, flexible data they provide.