Biology subjects

Plisson-Petit, F.

Publications and source records attributed to Plisson-Petit, F..

4 recordsLinked to original sources

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↗

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↗

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↗