Biology subjects

Sarry, J.

Publications and source records attributed to Sarry, J..

8 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↗

bioRxiv2023

A single base pair duplication in SLC33A1 gene causes fetal losses and neonatal lethality in Manech Tete Rousse dairy sheep

Recently, we evidenced that the Manech Tete Rousse (MTR) deficient homozygous haplotype 2 (MTRDHH2) was likely to harbor a recessive lethal variant in ovine. In the present study, we fine mapped this region by analyzing the whole genome sequence of five MTRDHH2 heterozygous carriers compared to 95 sequences of non-carrier animals from MTR and others ovine breeds. We successfully identified a single base pair duplication in the SLC33A1 gene, resulting in a frameshift leading to a premature stop codon (p.Arg246Alafs*3). SLC33A1 acts as a transmembrane transporter of acetyl-Coenzyme A, essential for cellular metabolism. In order to assess for the lethal phenotype in homozygous MTR sheep, we generated at-risk matings by artificial insemination (AI) between rams and ewes heterozygous for the SLC33A1 variant named SLC33A1_dupG. Gestation status was checked 15 days post-AI by a molecular test from blood expression of the interferon Tau-stimulated MX1 gene, and by ultrasonography performed between 45 days and 60 days post-AI. Based on ultrasonography, the AI success was reduced by 12% compared to safe matings suggesting embryonic/fetal losses further confirmed by the molecular test based on MX1 differential expression. Forty-nine lambs were born from at-risk matings with a mortality rate of 34.7% observed before weaning. Homozygous SLC33A1_dupG lambs contributed to 47% of this mortality occurring mainly in the first five days after lambing with no obvious clinical signs. Thus, an appropriate management of SLC33A1_dupG (allele frequency of 0.04) in the MTR selection scheme should increase the overall fertility and lamb survival.

genomics↗

bioRxiv2023

Homozygous haplotype deficiency in Manech Tete Rousse dairy sheep revealed a nonsense variant in MMUT gene affecting newborn lamb viability

Recessive deleterious variants are known to segregate in livestock populations as in human, and some may cause lethality when homozygous. By scanning the genome of 6,845 Manech Tete Rousse dairy sheep using phased 50k SNP genotypes and pedigree data, we searched for deficiency in homozygous haplotype (DHH). Five Manech Tete Rousse deficient homozygous haplotypes (MTRDHH1 to 5) were identified with a homozygous deficiency ranging from 84% to 100%. These haplotypes are located on OAR1 (MTRDHH2 and 3), OAR10 (MTRDHH4), OAR13 (MTRDHH5) and OAR20 (MTRDHH1), and have frequencies ranging from 7.8% to 16.6%. When comparing at-risk mating between DHH carriers to safe mating between non-carriers, two DHH (MTRDHH1 and 2) showed significant effects on decreasing artificial insemination success and/or increasing stillbirth rate. We particularly investigated the MTRDHH1 haplotype highly increasing stillbirth rate, and we identified a single nucleotide variant (SNV) inducing a premature stop codon (p.Gln409*) in the MMUT gene (methylmalonyl-CoA mutase) by using a whole genome sequencing (WGS) approach. We generated homozygous lambs for the MMUT mutation by oriented mating, and most of them died within the first 24h after birth without any obvious clinical defect. RT-qPCR and western blotting performed on post-mortem liver and kidney biological samples showed a decreased expression of MMUT mRNA in the liver and absence of a full-length MMUT protein in mutated homozygous lambs. In parallel, MTRDHH4 and MTRDHH5 showed partial association with variants in RXFP2 and ASIP genes, respectively, already known to control horned/polled and coat color phenotypes in sheep, two morphological traits accounting in the MTR breed standard. Further investigations are needed to identified the supposed recessive deleterious variant hosted by MTRDHH2 and MTRDHH3. Anyway, an appropriate management of these haplotypes/variants in the MTR dairy sheep selection program should increase the overall fertility and lamb survival. Author SummaryIn this article, we used reverse genetics screen in ovine using large genotype data available in the framework of genomic selection program in Manech Tete Rousse dairy sheep. We identified five genomic regions with a highly significant deficit in homozygous animal. These regions are thus supposed to host recessive deleterious mutations. In one of these genomic regions, we identified a nonsense mutation in MMUT that alters the functioning of this essential gene of cell metabolism, causing perinatal mortality of homozygous lambs. In this work, we also identified other regions possibly associated with morphological appearance part of the breed standard such as polledness and coat color. Increasing knowledge in these genomic regions will help the future genetic management of the Manech Tete Rousse breed, particularly to reduce lamb mortality.

genomics↗

bioRxiv2022

Stronger transcriptomic response to feed intake in the duodenum of pig with high feed efficiency from a divergent selection experiment

Feed efficiency is a trait of interest in pigs as it contributes to lowering the ecological and economical costs of pig production. A divergent genetic selection experiment from a Large White pig population was performed for 10 generations, leading to pig lines with relative low-(LRFI, more efficient) and high-(HRFI, less efficient) residual feed intake (RFI). Feeding behaviour and metabolic differences have been previously reported between the two lines. We hypothesised that part of these differences could be related to differential sensing and absorption of nutrients in the proximal intestine. Here we investigated the duodenum transcriptome and DNA methylation profiles comparing overnight fasting with ad libitum feeding in LRFI and HRFI pigs (n=24). We identified 1,106 differentially expressed genes between the two lines, notably affecting pathways of the transmembrane transport activity and related to mitosis or chromosome separation. The LRFI line showed a greater transcriptomic response to feed intake, with 2,222 differentially expressed genes before and after a meal, as compared to 61 differentially expressed genes in the HRFI line. Feed intake affected genes from both anabolic and catabolic pathways in the pig duodenum, such as rRNA production and autophagy. We noted that several nutrient transporter and tight junction genes were differentially expressed between lines and/or by short term feed intake. We also identified 409 differentially methylated regions in the duodenum mucosa between the two lines, while this epigenetic mark was less affected by feeding. However most of the differentially expressed genes were not associated with proximal changes in DNA methylation profiles. Altogether, our findings highlighted that the genetic selection for feed efficiency in pigs changed the transcriptome profiles of the duodenum, and notably its response to feed intake, suggesting key roles for this proximal gut segment in mechanisms underlying feed efficiency.

genomics↗

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↗