London Calling 2023: Discovering the missing variation: a long-read sequencing study into the structural variation in two dairy breeds

Structural Variants (SVs) have been demonstrated to play a substantial role in the evolution of species, and many SVs underpin a range of Mendelian and complex traits in the mammalian genome. However, in livestock, SV discovery and its application to livestock breeding have been limited by the technological limitations of short-read sequencing. Recent advances in the field of long-read sequencing have dramatically shifted this paradigm. We believe that, through a collaborative effort, it is now timely to apply long-read technology for population-scale SV discovery and imputation. In a pilot study, 20 Holstein (including two trios) and 20 Jersey cattle were sequenced using nanopore sequencing at an average read depth of ~20x. The data was then implemented in a scalable, reproducible workflow (nf-VALOR — VAriant discovery pipeline using LOng-Read sequencing) to detect SVs in the cohort. We will present results covering a range of aspects, from the effect of read depth on SV discovery to the variability within and between breeds, apportioned to SVs. This study revealed the power of long-read sequencing in targeting genome-wide large-size variants that might have massive phenotypic impact on livestock individuals.