Hayk Barseghyan, Andy W. C. Pang, Yang Zhang, Nikhil S. Sahajpal, Yannick Delpu, Chi-Yu Jill Lai, Joyce Lee, Chloe Tessereau, Mark Oldakowski, Ravindra B. Kolhe, Henry Houlden, Peter L. Nagy, Aaron D. Bossler, Alka Chaubey, Alex R. Hastie
Structural variants in the human genome have been associated with several neurological disorders. Syndromic neurodevelopmental delay has been reported to be caused by recurrent copy number variants (CNVs) at specific genomic loci as a result of non-allelic homologous recombination and concomitant inversions, translocations, deletions, or duplications accounting for some well-known developmental delay syndromes. Also, tandem repeat contractions and expansions can alter the function of several genes and result in a number of unique neuromuscular disorders, such as facioscapulohumeral muscular dystrophy type 1 (FSHD), fragile-X syndrome, and amyotrophic lateral sclerosis (ALS). As a result, genome-wide structural variation analysis is recommended for the accurate diagnosis of neurodevelopmental delay and intellectual disabilities. In addition to pediatric developmental disorders, somatic mosaicism in the brain has been reported in various genetic neurodegenerative disorders. In order to detect and study structural variants related to neurologic disorders, many genomic technologies are applied in clinical and translational research. Optical genome mapping (OGM) is a new method for the analysis of all classes of structural variants including CNVs, balanced translocations, inversions, repeat expansions, and repeat contractions. Furthermore, OGM allows the detection of mosaicism both for germ line and somatic variants. This single technology can therefore be applied to a broad range of clinically relevant structural variants.