Integrative genotyping and analysis of canine structural variation using long-read and short-read data

Abstract

Structural variation makes an important contribution to canine evolution and phenotypic differences. Although recent advances in long-read sequencing have enabled the generation of multiple canine genome assemblies, most prior analyses of structural variation have relied on short read sequencing. To offer a more complete assessment of structural variation in canines, we performed an integrative analysis of structural variants present in 12 canine samples with available long-read and short-read sequencing data along with genome assemblies. Use of long-reads permits the discovery of heterozygous variation that is absent in existing haploid assembly representations while offering a marked increase in the ability to identify insertion variants relative to short-read approaches. Examination of the size spectrum of structural variants shows that dimorphic LINE-1 and SINE variants account for over 45% of all deletions and identified 1,410 LINE-1s with intact open reading frames that show presence-absence dimorphism. Using a graph-based approach, we genotype newly discovered structural variants in an existing collection of 1,879 resequenced dogs and wolves, generating a variant catalog containing a 56.5% increase in the number of deletions and 705% increase in the number of insertions previously found in the analyzed samples. Examination of allele frequencies across admixture components present across breed clades identified 283 structural variants evolving with a signature of selection. Significance statementExisting studies of structural variation have focused on genomes sequenced with short-read technology. In this study, we systematically combine short-read and long-read data sets to identify and genotype structural variation across canines, resulting in an expanded catalog of structural variants. Analysis of allele frequencies identified structural variants in genic regions that may have been evolving under selection across breed clades.