Biology subjects

Drouilhet, L.

Publications and source records attributed to Drouilhet, L..

5 recordsLinked to original sources

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↗

bioRxiv2019

Genome-wide identification of a regulatory mutation in BMP15 controlling prolificacy in sheep

The search for the genetic determinism of prolificacy variability in sheep has evidenced several major mutations in genes playing a crucial role in the control of ovulation rate. In the Noire du Velay (NV) sheep population, a recent genetic study has evidenced the segregation of such a mutation named FecLL. However, based on litter size (LS) records of FecLL non-carrier ewes, the segregation of a second prolificacy major mutation was suspected in this population. In order to identify this mutation, we have combined case/control genome-wide association study with ovine 50k SNP chip genotyping, whole genome sequencing and functional analyses. A new single nucleotide polymorphism (OARX:50977717T>A, NC_019484) located on the X chromosome upstream of the BMP15 gene was evidenced highly associated with the prolificacy variability (P =1.93E-11). The variant allele was called FecXN and shown to segregate also in the Blanche du Massif Central (BMC) sheep population. In both NV and BMC, the FecXN allele frequency was estimated close to 0.10, and its effect on LS was estimated at +0.20 lamb per lambing at heterozygous state. Homozygous FecXN carrier ewes were fertile with increased prolificacy in contrast to numerous mutations affecting BMP15. At the molecular level, FecXN was shown to decrease BMP15 promoter activity and to impact BMP15 expression in oocyte. This regulatory action was proposed as the causal mechanism for the FecXN mutation to control ovulation rate and prolificacy in sheep. Author SummaryIn the genetic etiology of women infertility syndromes, a focus was done on the oocyte-expressed BMP15 and GDF9 genes harboring several mutations associated with ovarian dysfunctions. In sheep also, mutations in these two genes are known to affect the ovarian function leading to sterility or, on the opposite, increasing ovulation rate and litter size constituting the prolificacy trait genetically selected in this species. Through a genome-wide association study with the prolificacy phenotype conducted in the French Noire du Velay sheep breed, we describe a novel mutation located in the regulatory region upstream of the BMP15 gene on the X chromosome. This mutation increases litter size by +0.2 lamb per lambing at the heterozygous state, possibly through an inhibition of BMP15 expression within the oocyte. Our findings suggest a novel kind of BMP15 variant responsible for high prolificacy, in contrast to all other BMP15 variants described so far in the coding sequence.

genetics↗

bioRxiv2018

Presence of causative mutations affecting prolificacy in the Noire du Velay and Mouton Vendeen sheep breeds

For many decades, prolificacy has been selected in meat sheep breeds as a polygenic trait but with limited genetic gain. However, the discovery of major genes affecting prolificacy has changed the way of selection for some ovine breeds implementing gene-assisted selection as in the French Lacaune and Grivette meat breeds, or in the Spanish Rasa Aragonesa breed. Based on statistical analysis of litter size parameters from 34 French meat sheep populations, we suspected the segregation of a mutation in a major gene affecting prolificacy in the Noire du Velay and in the Mouton Vendeen breeds exhibiting a very high variability of the litter size. After the genotyping of mutations known to be present in French sheep breeds, we discovered the segregation of the FecLL mutation at the B4GALNT2 locus and the FecXGr mutation at the BMP15 locus in Noire du Velay and Mouton Vendeen, respectively. The frequency of ewes carrying FecLL in the Noire du Velay population was estimated at 21.2% and the Mouton Vendeen ewes carrying FecXGr at 10.3%. The estimated mutated allele effect of FecLL and FecXGron litter size at +0.4 and +0.3 lamb per lambing in Noire du Velay and Mouton Vendeen, respectively. Due to the fairly high frequency and the rather strong effect of the FecLL and FecXGr prolific alleles, specific management programmes including genotyping should be implemented for a breeding objective of prolificacy adapted to each of these breeds.

genetics↗

bioRxiv2017

Insights into the genetic determinism andevolution of recombination rates fromcombining multiple genome-wide datasets inSheep

Recombination is a complex biological process that results from a cascade of multiple events during meiosis. Understanding the genetic determinism of recombination can help to understand if and how these events are interacting. To tackle this question, we studied the patterns of recombination in sheep, using multiple approaches and datasets. We constructed male recombination maps in a dairy breed from the south of France (the Lacaune breed) at a fine scale by combining meiotic recombination rates from a large pedigree genotyped with a 50K SNP array and historical recombination rates from a sample of unrelated individuals genotyped with a 600K SNP array. This analysis revealed recombination patterns in sheep similar to other mammals but also genome regions that have likely been affected by directional and diversifying selection. We estimated the average recombination rate of Lacaune sheep at 1.5 cM/Mb, identified about 50,000 crossover hotspots on the genome and found a high correlation between historical and meiotic recombination rate estimates. A genome-wide association study revealed two major loci affecting inter-individual variation in recombination rate in Lacaune, including the RNF212 and HEI10 genes and possibly 2 other loci of smaller effects including the KCNJ15 and FSHR genes. Finally, we compared our results to those obtained previously in a distantly related population of domestic sheep, the Soay. This comparison revealed that Soay and Lacaune males have a very similar distribution of recombination along the genome and that the two datasets can be combined to create more precise male meiotic recombination maps in sheep. Despite their similar recombination maps, we show that Soay and Lacaune males exhibit different heritabilities and QTL effects for inter-individual variation in genome-wide recombination rates.

genetics↗