Biology subjects

Tosser-Klopp, G.

Publications and source records attributed to Tosser-Klopp, G..

13 recordsLinked to original sources

bioRxiv2026

Cromosomal genomes assemblies of twelve sheep breeds

The sheep research community benefits from a genome assembly that has been refined over the last 15 years. However, the rich diversity of sheep breeds suggests that a single individual genome is not enough to represent the species full genomic content. Third-generation sequencing technologies have recently made it possible to generate high quality assemblies that should enable to elucidate unique and/or complex phenotype determinisms depending on genetic structural variations. In the SeqOccin project, twelve breeds were selected to represent (mostly French) sheep genetic diversity: Basco-Bearnaise, Black Belly, Blanche du Massif Central, Corse, Ile de France, Lacaune, Manech Tete Noire, Noire du Velay, Ouessant, Rambouillet, Vendeen, Soay. High-molecular-weight DNA was extracted from blood samples and subjected to long read whole-genome sequencing. The reads were used to generate de novo assemblies and were aligned onto the public reference to call structural variants. PacBio HiFi and parental Illumina reads were used to assemble phased haplotypes of the Lacaune breed. For the other breeds, PacBio raw (CLR) or ONT reads were generated. Our work demonstrates the feasibility of assembling genomes with a reasonable amount of data and appropriate software packages, delivering one high-quality assembly and 11 standard sheep assemblies that pave the way for pangenome construction and structural variant functional studies.

genomics↗

bioRxiv2026

Goat genome assemblies, nine breeds for pangenome contribution

The goat research community benefits from one of the most comprehensive livestock genome assemblies, ARS1. However, the rich diversity of goat breeds suggests that a single individual genome is not enough to represent the species full genomic content. Third-generation sequencing technologies have recently made it possible to generate very high quality assemblies that should enable to elucidate unique and/or complex phenotype determinisms depending on genetic structural variations. In the SeqOccin project, nine goat breeds were selected to represent French goat genetic diversity: Alpine, Boer, Creole, Fosses, Poitevine, Provencale, Pyreneenne, Rove and Saanen. High-molecular-weight DNA was extracted from blood samples and subjected to long read whole-genome sequencing. There reads were used to generate de novo assemblies and were aligned onto the public reference to call structural variants. PacBio HiFi and parental Illumina reads were used to assemble phased haplotypes of the Alpine breed. For the other breeds, PacBio raw (CLR) or ONT reads were generated. Our work demonstrates the feasibility of assembling genomes with a reasonable amount of data and appropriate software packages, delivering one high-quality assembly and 8 standard goat assemblies that pave the way for pangenome construction and structural variant functional studies.

genomics↗

bioRxiv2026

Linking geography and mutation profiles across goat species

Recent studies have characterised the mutational profile across multiple mammalian species, highlighting substantial differences across lineages. However, none of these studies investigated whether mutation profiles and geography are significantly correlated. In this study, we present a multi-genome alignment spanning several Capra taxa, reconstruct the ancestral genome of Capra hircus and use it to characterize the mutational profiles across multiple Capra species by using the 1000 genomes VarGoats dataset. Results confirmed that the scale of differences among Capra species largely reflects their phylogenetic relationships, in particular with the Bezoar being genetically closer to domestic goats than to other wild species. Subsequently, we correlated the mutational profile and the geographical origin of the different individuals. In particular, ACG>ATG changes have the strongest correlation with longitude (r = -0.79, P-value = 3.02*10-204), while TCA>TGA are strongly correlated with latitude (r = -0.51, P-value = 4.30*10-63). We highlight how sequential dinucleotide mutations (SDMs) place cosmopolitan breeds closer to the sampling location, rather than the country of origin, showing how the recent relocation of cosmopolitan breeds to new continents is reshaping the genome of these animals. Finally, we used the mutational profile to predict the coordinate of origin of each animal in the dataset. In conclusion, we show the important role that geography had in shaping the genomes of domestic goats.

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

The variability of goat microRNA genes is strongly shaped by functional constraints

BackgroundMicroRNAs (miRNAs) are a type of small non-coding RNAs involved in the post-transcriptional repression of target mRNA transcripts, and responsible for the fine-tuning of numerous molecular mechanisms regulating cell metabolism. In goats, multiple miRNAs are involved in coordinating the expression of networks of genes with key roles on the phenotypic variation of milk and meat traits. Although a comprehensive set of goat miRNAs has been annotated, their levels of polymorphism have not been characterized yet. Such information would be relevant in order to explore the effects of miRNA variants on phenotypes of economic interest in goats. ResultsBy using whole-genome sequencing data from 770 domestic goats with African, Asian, and European origins, we have identified polymorphic sites located within miRNA genes as well as in their flanking regions. In doing so, we have found that miRNA polymorphisms are rare (median alternative allele frequency of 0.46%) and that the distribution of polymorphic sites within and around miRNA loci is uneven. Remarkably, the stem, loop and neighbouring regulatory regions of precursor miRNA hairpins show a significantly higher polymorphism density compared to the miRNA seed, which determines the binding affinity to target mRNAs. Moreover, we have detected a differential segregation of miRNA variants across and within continental regions, with an enriched segregation of putatively high impact polymorphisms, i.e. those located in the seed and other biologically relevant regions of miRNA genes, in isolated goat populations with a low census and elevated content of runs of homozygosity. ConclusionGoat miRNA genes display low levels of variation particularly in the seed region, likely due to the action of strong purifying selection removing mutations with potential effects on gene regulatory networks linked to miRNA function. Moreover, miRNA polymorphisms tend to be more abundant in goat breeds with high levels of homozygosity, likely because purifying selection is less efficient in populations of limited size. The information provided in the current work could be useful to identify miRNA polymorphisms contributing to phenotypic variation through the disruption of gene regulatory networks in domestic goats, as well as to assess their potential impact on adaptation and fitness.

genomics↗

bioRxiv2025

Inferring domestic goat demographic history through ancient genome imputation

Goats were among the earliest managed animals, making them a natural model to explore the genetic consequences of domestication. However, a challenge in ancient genomic analysis is the relatively low genome coverage for most samples, limiting analysis to pseudohaploid genotypes. Genotype imputation offers potential to alleviate this limitation by improving information content and accuracy in low coverage genomes. To test this we used published high coverage (>8x) goat palaeogenomes, imputing downsampled genomes using the VarGoats dataset (1,372 individuals) as a reference panel. Measuring concordance between imputed and high coverage genotypes, we find high concordance after filtering for common (>5%), high confidence variants, with 0.5x genomes reaching >0.97 concordance. There is a trade-off between coverage, genotype probability (GP) thresholds, and genotype recovery, where higher coverage and more lenient GP thresholds result in higher recovery, and a reduction in heterozygous false-positive rates with stricter thresholds. We then imputed 36 goat palaeogenomes with [≥]0.5x coverage to examine runs-of-homozygosity (ROH) and identity-by-descent (IBD) patterns. Using a novel approach combining ROH profiles across tools, we find that among Neolithic goats, ROH increases with distance from the Zagros Mountains, suggesting a large effect of the initial dispersal of managed herds. Inbreeding levels decrease across Southwest Asia in more recent periods. IBD mirrored this pattern, with less relatedness in the early herding site of Ganj Dareh compared to higher relatedness in goats from later in the dispersal process. These findings provide insights into the genetic consequences of early goat management on demography, and confirm the utility of imputation in leveraging low coverage palaeogenomes. SignificancePaleogenomics offers crucial insight into how animals were domesticated, but poor DNA preservation in ancient remains often limits the reach of genetic analyses. We utilise a cutting-edge technique, genotype imputation, to recover missing genetic information from ancient low coverage goat genomes and shine light on their domestication process. Early domestic goats showed low overall runs-of-homozygosity (ROH) and relatedness. We find that during the Neolithic, runs-of-homozygosity (ROH) and relatedness among goats increased, likely a consequence of the movement of herds beyond their natural range by humans. Inbreeding levels decline in more recent periods, potentially due to expanded herd sizes, animal trade networks, or improved husbandry practices. These findings challenge long-standing assumptions about domestication bottlenecks and highlight how ancient DNA can be used to uncover complex evolutionary histories, even from low coverage ancient samples.

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↗

bioRxiv2024

SMARTER-database: a tool to explore genomic diversity in small ruminants

Underutilized sheep and goat breeds have the ability to adapt to challenging environments due to their genetic composition. Integrating publicly available genomic datasets with new data will facilitate genetic diversity analyses; however, this process is complicated by important data discrepancies, such as outdated assembly versions or different data formats. Here we present the SMARTER-database, a collection of tools and scripts to standardize genomic data and metadata mainly from SNP chips arrays on global small ruminant populations with a focus on reproducibility. SMARTER-database harmonizes genotypes for about 12,000 sheep and 6,000 goats to a uniform coding and assembly version. Users can access the genotype data via FTP and interact with the metadata through a web interface or programmatically using their custom scripts, enabling efficient filtering and selection of samples. These tools will empower researchers to focus on the crucial aspects of adaptation and contribute to livestock sustainability, leveraging the rich dataset provided by the SMARTER-database. Availability & ImplementationThe code is available as open source software under the MIT license at https://github.com/cnr-ibba/SMARTER-database.

bioinformatics↗

bioRxiv2021

Local adaptations of Mediterranean sheep and goats through an integrative approach

In a context of climate change, identifying the genes underlying adaptations to extreme environments is essential. Small ruminants are adapted to a wide variety of habitats and thus, are promising study models. Here, we considered 17 goat and 25 sheep local Mediterranean breeds, in Italy, France and Spain. We proposed, and empirically tested a new methodology to highlight selection signatures in relation to the environments. Based on historical archives, we selected the breeds potentially most linked to a territory and defined their original geographical cradle, including transhumant pastoral areas. For both species, the cradles were arranged along latitudinal gradient of aridity and altitude. Then we used the programs PCAdapt and LFMM. Considering cradles, instead of current GPS coordinates, markedly improved the sensitivity of the LFMM analyses. All the results combined with a systematic literature review, revealed a set of genes with potentially key adaptive roles. Some of these genes, have been found implicated in lipid metabolism (SUCLG2, BMP2), hypoxia/heat stress (UBE2R2/UBAP2), lung function (BMPR2), seasonal patterns (SOX2, DPH6) or neuronal function (TRPC4, TRPC6). For the intergenic region between PCDH9 and KLH1, as well as NBEA, identified in both species, the adaptive role could be strong. We found for RXFP2, associated with sheep horn development, and MSRB3 and SLC26A4, both associated with hearing of sheep, a strong association with the environment gradient. We conclude that our new methodology, which considers breeds in their historical, environmental and anthropological context, provides novel and essential information on local breeds and their unique adaptations.

evolutionary biology↗

bioRxiv2020

Strongyle-resistant sheep express their potential across environments and leave limited scope for parasite plasticity

IntroductionDrug-resistant parasites threaten livestock production. Breeding more resistant hosts could be a sustainable control strategy. Environmental variation may however alter the expression of genetic potential and directional selection toward host resistance could initiate an arms race between the host and its parasites. Methods and ResultsWe created sheep lines with high or low resistance to Haemonchus contortus. We first exposed both lines to chronic stress or to the infection by another parasite Trichostrongylus colubriformis, to test for genotype-by-environment and genotype-by-parasite species interactions respectively. Overall, between-line divergence remained significant across environmental perturbations. But we found that the impact of chronic stress on H. contortus infection varied among families and that divergence was reduced during infection by T. colubriformis. Second, we quantified genomic and transcriptomic differences in H. contortus worms collected from both lines to identify components of an arms race. We found no evidence of genetic differentiation between worms from each line. But survival to more resistant hosts was associated with enhanced expression of cuticle collagen coding genes. DiscussionBreeding for resistance hence remains a sustainable strategy that requires to anticipate the effects of environmental perturbations and to monitor worm populations.

evolutionary biology↗

bioRxiv2019

RumimiR: a detailed microRNA database focused on ruminant species

In recent years, the increasing use of Next Generation Sequencing technologies to explore the genome has generated large quantities of data. For microRNAs, more and more publications have described several thousand sequences, all species included. In order to obtain a detailed description of microRNAs from the literature for three ruminant species (bovine, caprine and ovine), a new database has been created: RumimiR. To date, 2,887, 2,733 and 5,095 unique microRNAs of bovine, caprine and ovine species, respectively, have been included. In addition to the most recent reference genomic position and sequence of each microRNA, this database contains details on the animals, tissue origins and experimental conditions available from the publications. Identity with human or mouse microRNA is mentioned. The RumimiR database enables data filtering, the selection of microRNAs being based on defined criteria such as animal status or tissue origin. For ruminant studies, RumimiR supplements the widely used miRBase database by browsing and filtering using complementary criteria, and the integration of all published sequences described as novel. The principal goal of this database is to provide easy access to all ruminant microRNAs described in the literature.

genomics↗

bioRxiv2018

Livestock genome annotation: transcriptome and chromatin structure profiling in cattle, goat, chicken and pig.

BackgroundFunctional annotation of livestock genomes is a critical step to decipher the genotype-to-phenotype relationship underlying complex traits. As part of the Functional Annotation of Animal Genomes (FAANG) action, the FR-AgENCODE project (http://www.fragencode.org) aimed to profile the landscape of transcription (RNA-seq), chromatin accessibility (ATAC-seq) and conformation (Hi-C) in four livestock species representing ruminants (cattle, goat), monogastrics (pig) and birds (chicken), using three target samples related to metabolism (liver) and immunity (CD4+ and CD8+ T cells).\n\nResultsRNA-seq assays considerably extended the available catalog of annotated transcripts and identified differentially expressed genes with unknown function, including new syntenic lncRNAs. ATAC-seq highlighted an enrichment for transcription factor binding sites in differentially accessible regions of the chromatin. Comparative analyses revealed a core set of conserved regulatory regions across species. Topologically Associating Domains (TADs) and epigenetic A/B compartments annotated from Hi-C data were consistent with RNA-seq and ATAC-seq data. Multi-species comparisons showed that conserved TAD boundaries had stronger insulation properties than species-specific ones and that the genomic distribution of orthologous genes in A/B compartments was significantly conserved across species.\n\nConclusionsWe report the first multi-species and multi-assay genome annotation results obtained by a FAANG project. Beyond the generation of reference annotations and the confirmation of previous findings on model animals, the integrative analysis of data from multiple assays and species sheds a new light on the multi-scale selective pressure shaping genome organization from birds to mammals. Overall, these results emphasize the value of FAANG for research on domesticated animals and reinforces the importance of future meta-analyses of the reference datasets being generated by this community on different species.

genomics↗

bioRxiv2017

High density genome scan for selection signatures in French sheep reveals allelic heterogeneity and introgression at adaptive loci

Sheep was one of the first domesticated livestock species in the Anatolia region of contemporary Iran and eventually spread world-wide. Previous studies have shown that French sheep populations likely harbour a large part of European domesticated sheep diversity in a relatively small geographical region, offering a powerful model for the study of adaptation. We studied the diversity of 27 French sheep populations by genotyping 542 individuals for more than 500 000 SNPs. We found that French sheep breeds were divided into two main groups, corresponding to northern and southern origins and additionally we identified admixture events between northern and southern populations. The genetic diversity of domesticated animals results from adaptation of populations to constraints imposed by farmers and environmental conditions. We identified 126 genomic regions likely affected by selection. In many cases, we found evidence for parallel selection events in different genetic backgrounds, most likely for different mutations. Some of these regions harbour genes potentially involved in morphological traits (SOCS2, NCAPG/LCORL, MSRB3), coat colour (MC1R) and adaptation to environmental conditions (ADAMTS9). Closer inspection of two of these regions clarified their evolutionary history: at the LCORL/NCAPG locus we found evidence for introgression of an adaptive allele from a southern population into northern populations and by resequencing MC1R in some breeds we confirmed different mutations in this gene are responsible for the same phenotypic trait. Our study illustrates how dense genetic data in multiple populations allows the deciphering of evolutionary history of populations and of their adaptive mutations.

genetics↗