Remarkable progress has been made in the last decade in defining the importance of structural variation (SV) in human disease, and these studies have predominantly focused on copy number variation (CNV). However, a glaring blind spot exists in basic research and clinical diagnostic testing in our ability to detect genomic rearrangements that do not involve the gain or loss of genomic material, also known as balanced structural variation: neither clinical dosage arrays, nor genome-wide association studies, nor whole-exome sequencing, nor low-depth whole genome sequencing have been capable of detecting balanced chromosomal aberrations (including translocations, inversions, and insertions) or small CNVs. Our lab has long focused on developing whole genome sequencing methods to delineate these previously intractable variants and determining their role in neurological disorders. We have developed a new computational pipeline (GATK-SV) to solve the challenging problem of accurately detecting SV in large genome sequencing cohorts. This method has outperformed all comparable existing approaches and has been widely adopted by the human genomics community.
In our current pursuit of developing an atlas of structural variation across global populations, our lab is leading consortia efforts in the accurate detection of structural variations, including the Genome Aggregation Database (gnomAD) and All of Us.