Searching for homozygous haplotype deficiency in Manech Tête Rousse dairy sheep revealed a nonsense variant in the MMUT gene affecting newborn lamb viability.

BACKGROUND: Recessive deleterious variants are known to segregate in livestock populations, as in humans, and some may be lethal in the homozygous state. RESULTS: We used phased 50 k single nucleotide polymorphism (SNP) genotypes and pedigree data to scan the genome of 6845 Manech Tête Rousse dairy sheep to search for deficiency in homozygous haplotypes (DHH). Five Manech Tête Rousse deficient homozygous haplotypes (MTRDHH1 to 5) were identified, with a homozygous deficiency ranging from 84 to 100%. These haplotypes are located on Ovis aries chromosome (OAR)1 (MTRDHH2 and 3), OAR10 (MTRDHH4), OAR13 (MTRDHH5), and OAR20 (MTRDHH1), and have carrier frequencies ranging from 7.8 to 16.6%. When comparing at-risk matings between DHH carriers to safe matings between non-carriers, two DHH (MTRDHH1 and 2) were linked with decreased insemination success and/or increased stillbirth incidence. We investigated the MTRDHH1 haplotype, which substantially increased stillbirth rate, and identified a single nucleotide variant (SNV) inducing a premature stop codon (p.Gln409*) in the methylmalonyl-CoA mutase (MMUT) gene by using a whole-genome sequencing approach. We generated homozygous lambs for the MMUT mutation by at-risk mating between heterozygous carriers, and most of them died within the first 24 h after birth without any obvious clinical symptoms. Reverse transcriptase-qPCR and western blotting 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 the mutant homozygous lambs. CONCLUSIONS: We identified five homozygous deficient haplotypes that are likely to harbor five independent deleterious recessive variants in sheep. One of these was detected in the MMUT gene, which is associated with lamb lethality in the homozygous state. A specific management of these haplotypes/variants in the MTR dairy sheep selection program would help enhance the overall fertility and lamb survival.

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%.

Investigation of Lithium Insertion Mechanisms of a Thin-Film Si Electrode by Coupling Time-of-Flight Secondary-Ion Mass Spectrometry, X-ray Photoelectron Spectroscopy, and Focused-Ion-Beam/SEM.

Silicon is a serious candidate to replace graphite in electrodes because it offers a specific capacity almost 10 times higher than that of carbonaceous materials. However, cycling performances of Si electrodes remain very limited because of the huge volume changes upon alloying and dealloying with lithium. A fine understanding of the lithiation mechanism of silicon electrodes will help to design more robust architectures. In this work, an amorphous silicon thin film has been used as a model for a better understanding of lithiation mechanism. Lithium distribution in the Si layer has been thoroughly investigated by coupling powerful characterization tools: X-ray photoelectron spectroscopy (XPS) and secondary-ion mass spectrometry (ToF-SIMS). In particular, cross-analysis of different lithiation states has been carried out. A lithiation front moving forward over the state of charge has been highlighted. The quantification of the LixSi alloy indicates a lithium amount much higher than that of the Li/Si ratio estimated in previous studies. This anomaly leads to a description of the lithiation mechanism based on the presence of fast diffusion paths for Li throughout the Si layer. These paths would be a second driving force for silicon alloying and lithium segregation at the collector interface. SEM observations of a FIB cut corroborate this mechanism.

One-step synthesis of Si@C nanoparticles by laser pyrolysis: high-capacity anode material for lithium-ion batteries.

Carbon-covered silicon nanoparticles (Si@C) were synthesized for the first time by a one-step continuous process in a novel two stages laser pyrolysis reactor. Crystallized silicon cores formed in a first stage were covered in the second stage by a continuous shell mainly consisting in low organized sp(2) carbon. At the Si/C interface silicon carbide is absent. Moreover, the presence of silicon oxide is reduced compared to materials synthesized in several steps, allowing the use of such material as promising anode material in lithium-ion batteries (LIB). Auger Electron Spectroscopy (AES) analysis of the samples at both SiKLL and SiLVV edges proved the uniformity of the carbon coating. Cyclic voltammetry was used to compare the stability of Si and Si@C active materials. In half-cell configuration, Si@C exhibits a high and stable capacity of 2400 mAh g(-1) at C/10 and up to 500 mAh g(-1) over 500 cycles at 2C. The retention of the capacity is attributed to the protective effect of the carbon shell, which avoids direct contact between the silicon surface and the electrolyte.