Dissecting genome dosage, structure and function by whole genome sequencing

The structure and dosage of an organism’s chromosomes are precisely maintained and, when altered, can have severe phenotypic consequences. While the study of structural chromosomal changes can provide valuable insight on genome function, use of the required tools and assays in a range of species can be challenging. We recently described a sensitive approach that is able to detect altered dosage by using whole genome sequencing. This technique can be applied to data obtained from a wide array of samples derived from either PCR-free, amplified or exome-capture libraries. For example, we were able to detect haplotype-specific aneuploidy resulting from chromothripsis in plants. Further analysis using the resulting dosage plots provided the precise structural rearrangements induced by chromothripsis. We plan to use this method to characterize a population of individuals that have undergone chromothripsis in order to study the effects of these extreme genomic changes across multiple generations.