Biology subjects

Birbes, C.

Publications and source records attributed to Birbes, C..

4 recordsLinked to original sources

bioRxiv2025

Comprehensive detection of structural variations in long and short reads dataset of French cattle

Structural variants (SVs) correspond to different types of genomic variants larger than 50 bp. Many findings suggest the use of long rather than short reads to improve the accuracy of SV detection. Here, we present the results of an in-depth analysis for detection of SVs, mainly large insertions and deletions, in 14 French bovine breeds, based on whole-genome data comprising 176 long-read and 571 short-read samples, with 154 individuals having both long- and short-read data available. We first investigated possible biases on the performances of well-known SV detection tools, namely CUTESV, PBSV, and SNIFFLES, using long reads from different technologies, including PacBio HiFi, Oxford ONT, and PacBio CLR. We subsequently highlighted the abilities of tools for detecting SVs (DELLY, LUMPY, and MANTA) and for genotyping known SVs (GRAPHTYPER, SVTYPER, PARAGRAPH, and VG toolkit) using short-read data. We then show how the incremental composition of samples in the reference panel affected the SV genotyping for six validation individuals sequenced in short reads. We then searched for the optimal parameters and created the final SV reference panel consisting of 25,191 deletions and 30,118 insertions. Finally, we emphasized the landscape of the genotyped SVs segregating across 571 short-read individuals of 14 breeds.

genomics↗

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↗

bioRxiv2025

Benchmarking long-read genome assemblers for three sequencing protocols and three agricultural species

Today, long read technologies make it possible to produce telomere-to-telomere genome assemblies. These assemblies permit more accurate whole genome analyses, including on repeated regions. The genome assembly process can chain several steps such as read correction, contigs assembly, contig polishing, scaffolding and gap filling, among others. Each step usually requires at least one software package, and input sequences. For the end user, it is not necessarily clear which combination of tools, together with read types, will work best for a given genome. In this work, we will focus on contig production, which is a central and complex task of the assembly process. It aims at producing the longest, errorless, sequences, called contigs, from reads. While it is possible to produce contigs from short reads, long reads are now widely preferred, since they produce much longer contigs. In this work, we evaluate several contig producing software packages (usually named assemblers), on long reads generated by two sequencers using three protocols, for three eukaryotic, complex species with different characteristics. Our aim is twofold. First, we would like to give readers insight on the impact of sequencing technology and assembler combinations, in order to help them make their choice for a given genome. Second, we would like to present different assembly metrics and provide a critical view on their interpretation.

bioinformatics↗

bioRxiv2023

Massive detection of cryptic recessive genetic defects in cattle mining millions of life histories

We present a data-mining framework designed to detect recessive defects in livestock that have been previously missed due to a lack of specific signs, incomplete penetrance, or incomplete linkage disequilibrium. This approach leverages the massive data generated by genomic selection. Its basic principle is to compare the observed and expected numbers of homozygotes for sliding haplotypes in animals with different life histories. Within three cattle breeds, we report 33 new loci responsible for increased risk of juvenile mortality and present a series of validations based on large-scale genotyping, clinical examination, and functional studies for candidate variants affecting the NOA1, RFC5, and ITGB7 genes. In particular, we describe disorders associated with NOA1 and RFC5 mutations for the first time in vertebrates. The discovery of these many new defects will help to characterize the genetic basis of inbreeding depression, while their management will improve animal welfare and reduce losses to the industry.

genetics↗