Following our initial studies characterizing structural variation detected by cytogenetic methods at sequence resolution, we have pursued the delineation of ‘cryptic’ classes of structural variation, or variants not detectable at cytogenetic resolution. In two recent studies, we have discovered that cryptic and complex rearrangements that are cryptic to cytogenetic methods represent a major component of all genomic structural variation. We have also delineated a new class of structural variation, two duplications in proximity that flank a cryptic inversion, which we denote as dupINVdup, that occur with striking frequency (~8% of all probands in one ASD cohort studied). We also find that a high proportion of duplications in the genome are misclassified by microarray and actually mark complex structural variants, and that, remarkably, only ~35-40% of the inversions in the human genome are simple, or canonical, inversions; the remainder harbor additional sequence complexity. These new findings are described in two recent publications from the lab, and each has significant implications for structural variation sequencing studies as well as clinical diagnostic testing by microarray.
Brand et al., 2014, AJHG
Brand*, Collins* et al., 2015, AJHG