During last decades there has been a great interest in the characterization of all human genomic variation and its association with phenotypic traits and disease susceptibility. Most studies have focused on single nucleotide changes (SNPs), but they have been able to explain just a small part of the genetic risk for common and complex diseases. The discovery of a large amount of structural variants (SVs), which affect bigger segments of DNA and could have greater functional consequences, suggested that they could account for this missing heritability. Nevertheless, the study of SVs has been hindered by the lack of a comprehensive catalogue of variants and the difficulty to identify them in multiple individuals. This is especially problematic for inversions, which, due to their balanced nature and the presence of highly identical inverted repeats (IRs) at the breakpoints, are largely undetected with even most high-throughput sequencing techniques. Here, we propose a novel computational pipeline to genotype inversions by the detection of Oxford Nanopore long reads spanning inversion breakpoints using probe sequences located both outside and inside inverted regions. This methodology shows great promise for the characterization of previously missed inversions in multiple individuals, contributing to generate a more complete picture of human genetic variation.
Gonzalo Merino