Oligonucleotide microarrays for clinical diagnosis of copy number variation and zygosity status

Detection of submicroscopic genomic copy number variation is now considered the first-tier clinical test-in place of standard G-banded karyotyping-in the evaluation of children with unexplained developmental delay, intellectual disability, autism spectrum disorders, or congenital anomalies. Fluorescence in situ hybridization (FISH) was the first molecular method for detection of submicroscopic genomic copy number variants (CNVs), but microarray-based comparative genomic hybridization (array CGH) has a much higher diagnostic yield for these patients when compared to traditional cytogenetic methods such as karyotype and FISH. This unit focuses on oligonucleotide arrays, including updated information about detection of long contiguous stretches of homozygosity (LCSH) through inclusion of single-nucleotide polymorphism (SNP) probes. Most clinical laboratories now offer arrays with some level of probe coverage throughout the genome, and many are offering detection of LCSH. Updated guidelines for array design and result interpretation are reviewed.