Biology subjects

Sorin, V.

Publications and source records attributed to Sorin, V..

3 recordsLinked to original sources

bioRxiv2026

Integrating Structural Variants into Sequence-Based GWAS Using a Pangenome and Imputation Framework in French Dairy Cattle

BackgroundStructural variants (SVs) are most effectively identified using long-read (LR) sequenc-ing. However, such data remain scarce, and sequenced samples often lack associated phenotypic information. To overcome this limitation, we integrated pangenome-based (variation graph-based) and imputation approaches to enable large-scale SV association studies in the three main French dairy cattle breeds. ResultsA variation graph was constructed using 69,892 deletions, 89,900 insertions, and 17,402 duplications detected in 176 LR samples. We subsequently genotyped 939 samples for each SV in the panel by realigning their short read (SR) sequences to the graph. Validation analyses showed high genotype concordance rates for deletions (0.79) and insertions (0.79); however, concordance for duplications was low (0.14), leading to their exclusion from further analyses. The retained SVs were combined with single nucleotide variants (SNVs) to build a sequence-level imputation reference panel. Using SNP genotyping array data, we imputed SVs and SNVs for 11,902 Holstein, 3,753 Montbeliarde, and 3,053 Normande bulls. After quality control, more than 14 million SNVs and 40 thousand SVs were retained for within-breed genome-wide association studies (GWAS) us-ing daughter yield deviations for stature and four milk production and composition traits. The GWAS results reveled genetic architectures consistent with previous findings and identified 40 genome-wide significant associations between structural variant and key phenotypes. Conditional analyses showed that ten of these SVs as strong candidates associated with milk fat and protein contents, as well as stature. ConclusionsBy integrating LR, SR, and SNP genotyping data within a unified pangenome and imputation framework, we demonstrate a scalable strategy to systematically interrogate the contribution of SVs to complex traits. The resulting genetic architectures were highly consistent with previous findings, validating both the robustness and transferability of our approach. Our findings highlight the added value of integrating SVs into routine genomic analyses and provide a scalable framework for incorporating SVs into genomic selection in dairy cattle.

genomics↗

bioRxiv2025

Assembly of a pangenome uncovers novel non-reference unique insertion sequences in cattle highlighting their genetic diversity

BackgroundThe current cattle reference genome, derived from a single Hereford cow, does not capture the full spectrum of genetic diversity present within the species. Moreover, detecting structural variations (SVs [≥] 50 nucleotides long) remains challenging using only standard approaches of either short or long-read sequence approaches against a linear reference genome. Recent advances in long-read sequencing technologies and graph-based assembly now enable the construction of breed-specific pangenomes, revealing previously uncharacterized genomic regions that may contribute to important agricultural traits. ResultsIn this study we constructed a cattle pangenome graph using 16 high-quality haplotype-resolved genome assemblies originating from nine breeds representing the diversity of French cattle populations, and including Yak (Bos grunniens) as a close outgroup species. Using a trio-based strategy combined with complementary sequencing technologies and bioinformatics methods, we identified and characterized 101,219 structural variations. Of these, 33,634 were classified as non-reference unique insertions (NRUIs), adding several megabases of novel genomic sequences absent from the current Hereford reference genome. Analysis of the distribution of these NRUIs revealed significant genome-wide enrichment within QTL regions associated with milk production and morphological traits, suggesting their contribution to the genetic basis of economically relevant phenotypes. Furthermore, their functional annotation highlighted two NRUIs located within the intronic regions of ARMH3 and EPHA5, both specific to the Normande breed and significantly associated with milk production and morphological traits, respectively. ConclusionsOur findings demonstrate the value of pangenome approaches to uncover functionally relevant SVs, particularly NRUIs, that are systematically not in the current reference genome. By linking these variants to economically important traits, our work underscores the need to incorporate breed diversity into future genomic analyses and reference-building efforts in cattle.

genetics↗

bioRxiv2025

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

BackgroundThe current cattle reference genome assembly, a pseudo-linear sequence produced using sequences from a single Hereford cow, represent a limit 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 short or long-read sequence mapping to the current bovine genome assembly. ResultsIn this study, we used long-reads (LR) and bioinformatic tools to construct a comprehensive bovine pangenome 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 Hereford reference genome assembly. Our analysis also revealed 109,275 SVs, of which 84,612 were bi-allelic, including 21,840 insertions and 21,340 deletions. Genome-wide association studies using SNPs and a panel of 221 SVs, shared between the pangenome and the EuroGMD chip, revealed several well-known QTLs across the genome for the Holstein, Montbeliarde and Normande breeds. Among those, a QTL on chromosome 11 presents an SV with a highly significant effect on stature in the Holstein breed. This SV is a 6.2 kb deletion affecting the 5UTR, first exon and part of first intron of MATN3 gene, suggesting a potential regulatory and coding effect. ConclusionsOur study provides new insights into the genetic diversity of 14 French dairy and beef breeds and highlights the utility of pangenome graphs in capturing structural variation. The identified SV associated with stature highlights the importance of integrating SVs into GWAS for a more comprehensive understanding of complex traits.

genetics↗