Application of a French cattle pangenome, from structural variant discovery to association studies on key phenotypes

作者：Valentin Sorin, Maulana M. Naji, Clément Birbes, Cécile Grohs, Clémentine Escouflaire, Sébastien Fritz, Camille Eché, Camille Marcuzzo, Amandine Suin, Cécile Donnadieu, Christine Gaspin, Carole Iampietro, Denis Milan, Laurence Drouilhet, Gwenola Tosser-Klopp, Didier Boichard, Christophe Klopp, Marie-Pierre Sanchez, Mekki Boussaha · 发表于：Genetics Selection Evolution · 年份：2025 · DOI：10.1186/s12711-025-01012-x · 被引用次数：5 · 研究领域：Genetic and phenotypic traits in livestock、Genetic Mapping and Diversity in Plants and Animals、Genomics and Phylogenetic Studies

BACKGROUND: The current cattle reference genome assembly, a pseudo-linear sequence produced using sequences from a single Hereford cow, represents a limitation when performing genetic studies, especially when investigating the whole spectrum of genetic variations within the species. Detecting structural variations (SVs) poses significant challenges when relying solely on conventional methods of sequencing read mapping to the current bovine genome assembly. RESULTS: In this study, we used long-reads (LR) and bioinformatic tools to construct a comprehensive bovine pangenome, using as a backbone the Hereford ARS-UCD1.2 reference genome assembly, and incorporating genetic diversity of 64 good quality de novo genome assemblies representing 14 French dairy and beef cattle breeds. Using a combination of complementary approaches, we explored the pangenome graph and identified 2.563 Gb of sequences common to all samples, and cumulated 0.295 Gb of variable sequences. Notably, we discovered 0.159 Gb of novel sequences not present in the current reference genome assembly. Our analysis also revealed 109,275 SVs, of which 84,612 were bi-allelic. These included 27,171 insertions and 24,592 deletions, while the remaining 32,849 SVs corresponded to alternate allele sequences defined as sequence substitutions between the reference genome and the sample sequence. Genome-wide association studies using SNPs and a panel of 221 SVs, shared between the pangenome and the EuroGMD chip, revealed well-k...