A genome scan for milk production traits in dairy goats reveals two new mutations in <i>Dgat1</i> reducing milk fat content

The quantity of milk and milk fat and proteins are particularly important traits in dairy livestock. However, little is known about the regions of the genome that influence these traits in goats. We conducted a genome wide association study in French goats and identified 109 regions associated with dairy traits. For a major region on chromosome 14 closely associated with fat content, the Diacylglycerol O-Acyltransferase 1 (DGAT1) gene turned out to be a functional and positional candidate gene. The caprine reference sequence of this gene was completed and 29 polymorphisms were found in the gene sequence, including two novel exonic mutations: R251L and R396W, leading to substitutions in the protein sequence. The R251L mutation was found in the Saanen breed at a frequency of 3.5% and the R396W mutation both in the Saanen and Alpine breeds at a frequencies of 13% and 7% respectively. The R396W mutation explained 46% of the genetic variance of the trait, and the R251L mutation 6%. Both mutations were associated with a notable decrease in milk fat content. Their causality was then demonstrated by a functional test. These results provide new knowledge on the genetic basis of milk synthesis and will help improve the management of the French dairy goat breeding program

Author Correction:A genome scan for milk production traits in dairy goats reveals two new mutations in Dgat1 reducing milk fat content (Scientific Reports DOI: 10.1038/s41598-017-02052-0)

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Identification of two major genes affecting prolificacy in the French Noire du Velay sheep

Identification of two major genes affecting prolificacy in the French Noire du Velay sheep. 36. Conference of the International Society for Animal Genetics (ISAG

Detection of single nucleotide polymorphisms at major prolificacy genes in the Mehraban sheep and association with litter size

The present study aimed to investigate the presence of polymorphism at four known genes controlling ovine prolificacy i.e. BMP15, GDF9, BMPR1B and B4GALNT2 in a sample of 115 Iranian Mehraban ewes and their association with litter size (LS) and lambs' birth weight (BW) traits. Using Sanger sequencing of exons and polymorphism specific genotyping, ten SNPs (Single Nucleotide Polymorphisms) were observed in only two genes, GDF9 and BMPR1B. Seven SNPs were found in the GDF9 gene on the chromosome 5. Among them, six were already described in the coding sequence, and a new one (g.41840985C>T) was found in the 3'UTR. In the BMPR1B gene on the chromosome 6, three novel SNPs were detected in the exon 7 (g.29382184G>A; g.29382337G>A and g.29382340G>A). Allelic frequencies were established for six SNPs among the ten identified and they were in Hardy-Weinberg equilibrium. A significant association was found between the novel SNPs found in the exon 7 of BMPR1B and LS. Present results indicate the potential role of the BMPR1B locus in controlling prolificacy of Mehraban sheep and provide genetic markers for further exploitation in selection to improve reproductive efficiency

Presence of causative mutations affecting prolificacy in the Noire du Velay and Mouton Vendéen 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 FecL(L) mutation at the B4GALNT2 locus and the FecX(Gr) mutation at the BMP15 locus in Noire du Velay and Mouton Vendeen, respectively. The frequency of ewes carrying FecL(L) in the Noire du Velay population was estimated at 21.2% and the Mouton Vendeen ewes carrying FecX(Gr) at 10.3%. The estimated mutated allele effect of FecL(L) and FecX(Gr) on 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 FecL(L) and FecX(Gr) prolific alleles, specific management programmes including genotyping should be implemented for a breeding objective of prolificacy adapted to each of these breeds

A Nonsense Variant in CCDC65 Gene Causes Respiratory Failure Associated with Increased Lamb Mortality in French Lacaune Dairy Sheep

We recently demonstrated that the Lacaune deficient homozygous haplotype 6 (LDHH6) potentially hosts a recessive perinatal lethal mutation in Lacaune dairy sheep mapped on OAR3. In the present study, we have analyzed the whole-genome sequences of two Lacaune ram heterozygous carriers of LDHH6. After variant calling and filtering against the variants of 86 non-carrier rams, we have identified a single nucleotide variant (SNV) in the two LDHH6 carriers whose variant allele induced a premature stop codon (p.Glu111*) in the Coiled-Coil Domain Containing 65 (CCDC65) gene. CCDC65 is involved in the assembly of the nexin-dynein regulatory complex for the formation of microtubules in ciliated cells. In order to identify the phenotype in homozygous sheep, we generated at-risk matings (n = 17) between rams and ewes heterozygous for the candidate variant in CCDC65. A total of 16 lambs were born alive with five genotyped as homozygous carriers. The homozygous lambs suffered from respiratory problems, and four of them died within the first month of life. At necropsy, we observed a broad hepatization of lung lobes possibly induced by infectious pneumonia. The management of this lethal recessive allele (frequency of 0.06) through reasoned mating in the Lacaune sheep selection schemes could reduce lamb mortality by 2%

FecX(Bar) a Novel BMP15 mutation responsible for prolificacy and female sterility in Tunisian Barbarine Sheep

Naturally occurring mutations in growth and differentiation factor 9 (GDF9) or bone morphogenetic protein 15 (BMP15) genes are associated with increased ovulation rate (OR) and litter size (LS) but also sterility. Observing the Tunisian Barbarine ewes of the "W" flock selected for improved prolificacy, we found prolific and infertile ewes with streaky ovaries. Blood genomic DNA was extracted from a subset of low-ovulating, prolific and infertile ewes of the "W" flock, and the entire coding sequences of GDF9 and BMP15 were sequenced. We evidenced a novel polymorphism in the exon 1 of the BMP15 gene associated with increased prolificacy and sterility. This novel mutation called FecX(Bar) is a composite polymorphism associating a single nucleotide substitution (c.301G > T), a 3 bp deletion (c. 302_304delCTA) and a C insertion (c. 310insC) in the ovine BMP15 cDNA leading to a frame shift at protein position 101. Calculated in the "W" flock, the FecX(Bar) allele increased OR by 0.7 ova and LS by 0.3 lambs (p = 0.08). As for already identified mutations, homozygous females carrying FecX(Bar) exhibited streaky ovaries with a blockade at the primary stage of folliculogenesis as shown by histochemistry. Our investigation demonstrates a new mutation in the BMP15 gene providing a valuable genetic tool to control fecundity in Tunisian Barbarine, usable for diffusion program into conventional flocks looking for prolificacy improvement

An overview of gene expression dynamics during early ovarian folliculogenesis: specificity of follicular compartments and bi-directional dialog

Chantier qualité GABackground: Successful early folliculogenesis is crucial for female reproductive function. It requires appropriate gene specific expression of the different types of ovarian cells at different developmental stages. To date, most gene expression studies on the ovary were conducted in rodents and did not distinguish the type of cell. In mono-ovulating species, few studies have addressed gene expression profiles and mainly concerned human oocytes. Results: We used a laser capture microdissection method combined with RNA-seq technology to explore the transcriptome in oocytes and granulosa cells (GCs) during development of the sheep ovarian follicle. We first documented the expression profile of 15 349 genes, then focused on the 5 129 genes showing differential expression between oocytes and GCs. Enriched functional categories such as oocyte meiotic arrest and GC steroid synthesis reflect two distinct cell fates. We identified the implication of GC signal transduction pathways such as SHH, WNT and RHO GTPase. In addition, signaling pathways (VEGF, NOTCH, IGF1, etc.) and GC transzonal projections suggest the existence of complex cell-cell interactions. Finally, we highlighted several transcription regulators and specifically expressed genes that likely play an important role in early folliculogenesis. Conclusions: To our knowledge, this is the first comprehensive exploration of transcriptomes derived from in vivo oocytes and GCs at key stages in early follicular development in sheep. Collectively, our data advance our understanding of early folliculogenesis in mono-ovulating species and will be a valuable resource for unraveling human ovarian dysfunction such as premature ovarian failure (POF)