Enhancing Animal Disease Resistance, Production Efficiency, and Welfare through Precise Genome Editing.

The major goal of animal breeding is the genetic enhancement of economic traits. The CRISPR/Cas system, which includes nuclease-mediated and base editor mediated genome editing tools, provides an unprecedented approach to modify the mammalian genome. Thus, farm animal genetic engineering and genetic manipulation have been fundamentally revolutionized. Agricultural animals with traits of interest can be obtained in just one generation (and without long time selection). Here, we reviewed the advancements of the CRISPR (Clustered regularly interspaced short palindromic repeats)/Cas (CRISPR associated proteins) genome editing tools and their applications in animal breeding, especially in improving disease resistance, production performance, and animal welfare. Additionally, we covered the regulations on genome-edited animals (GEAs) and ways to accelerate their use. Recommendations for how to produce GEAs were also discussed. Despite the current challenges, we believe that genome editing breeding and GEAs will be available in the near future.

The differentiation state of the Schwann cell progenitor drives phenotypic variation between two contagious cancers.

Contagious cancers are a rare pathogenic phenomenon in which cancer cells gain the ability to spread between genetically distinct hosts. Nine examples have been identified across marine bivalves, dogs and Tasmanian devils, but the Tasmanian devil is the only mammalian species known to have given rise to two distinct lineages of contagious cancer, termed Devil Facial Tumour 1 (DFT1) and 2 (DFT2). Remarkably, DFT1 and DFT2 arose independently from the same cell type, a Schwann cell, and while their ultra-structural features are highly similar they exhibit variation in their mutational signatures and infection dynamics. As such, DFT1 and DFT2 provide a unique framework for investigating how a common progenitor cell can give rise to distinct contagious cancers. Using a proteomics approach, we show that DFT1 and DFT2 are derived from Schwann cells in different differentiation states, with DFT2 carrying a molecular signature of a less well differentiated Schwann cell. Under inflammatory signals DFT1 and DFT2 have different gene expression profiles, most notably involving Schwann cell markers of differentiation, reflecting the influence of their distinct origins. Further, DFT2 cells express immune cell markers typically expressed during nerve repair, consistent with an ability to manipulate their extracellular environment, facilitating the cell's ability to transmit between individuals. The emergence of two contagious cancers in the Tasmanian devil suggests that the inherent plasticity of Schwann cells confers a vulnerability to the formation of contagious cancers.

Breeding for Virus Resistance and Its Effects on Deformed Wing Virus Infection Patterns in Honey Bee Queens.

Viruses, and in particular the deformed wing virus (DWV), are considered as one of the main antagonists of honey bee health. The 'suppressed in ovo virus infection' trait (SOV) described for the first time that control of a virus infection can be achieved from genetically inherited traits and that the virus state of the eggs is indicative for this. This research aims to explore the effect of the SOV trait on DWV infections in queens descending from both SOV-positive (QDS+) and SOV-negative (QDS-) queens. Twenty QDS+ and QDS- were reared from each time four queens in the same starter-finisher colony. From each queen the head, thorax, ovaries, spermatheca, guts and eviscerated abdomen were dissected and screened for the presence of the DWV-A and DWV-B genotype using qRT-PCR. Queens descending from SOV-positive queens showed significant lower infection loads for DWV-A and DWV-B as well as a lower number of infected tissues for DWV-A. Surprisingly, differences were less expressed in the reproductive tissues, the ovaries and spermatheca. These results confirm that selection on the SOV trait is associated with increased virus resistance across viral genotypes and that this selection drives DWV towards an increased tissue specificity for the reproductive tissues. Further research is needed to explore the mechanisms underlying the interaction between the antiviral response and DWV.

Global mRNA and miRNA Analysis Reveal Key Processes in the Initial Response to Infection with WSSV in the Pacific Whiteleg Shrimp.

White Spot Disease (WSD) presents a major barrier to penaeid shrimp production. Mechanisms underlying White Spot Syndrome Virus (WSSV) susceptibility in penaeids are poorly understood due to limited information related to early infection. We investigated mRNA and miRNA transcription in Penaeus vannamei over 36 h following infection. Over this time course, 6192 transcripts and 27 miRNAs were differentially expressed-with limited differential expression from 3-12 h post injection (hpi) and a more significant transcriptional response associated with the onset of disease symptoms (24 hpi). During early infection, regulated processes included cytoskeletal remodelling and alterations in phagocytic activity that may assist WSSV entry and translocation, novel miRNA-induced metabolic shifts, and the downregulation of ATP-dependent proton transporter subunits that may impair cellular recycling. During later infection, uncoupling of the electron transport chain may drive cellular dysfunction and lead to high mortalities in infected penaeids. We propose that post-transcriptional silencing of the immune priming gene Dscam (downregulated following infections) by a novel shrimp miRNA (Pva-pmiR-78; upregulated) as a potential mechanism preventing future recognition of WSSV that may be suppressed in surviving shrimp. Our findings improve our understanding of WSD pathogenesis in P. vannamei and provide potential avenues for future development of prophylactics and treatments.

Transcriptome-level assessment of the impact of deformed wing virus on honey bee larvae.

Deformed wing virus (DWV) prevalence is high in honey bee (Apis mellifera) populations. The virus infects honey bees through vertical and horizontal transmission, leading to behavioural changes, wing deformity, and early mortality. To better understand the impacts of viral infection in the larval stage of honey bees, artificially reared honey bee larvae were infected with DWV (1.55 × 1010 copies/per larva). No significant mortality occurred in infected honey bee larvae, while the survival rates decreased significantly at the pupal stage. Examination of DWV replication revealed that viral replication began at 2 days post inoculation (d.p.i.), increased dramatically to 4 d.p.i., and then continuously increased in the pupal stage. To better understand the impact of DWV on the larval stage, DWV-infected and control groups were subjected to transcriptomic analysis at 4 d.p.i. Two hundred fifty-five differentially expressed genes (DEGs) (fold change ≥ 2 or ≤ -2) were identified. Of these DEGs, 168 genes were downregulated, and 87 genes were upregulated. Gene Ontology (GO) analysis showed that 141 DEGs (55.3%) were categorized into molecular functions, cellular components and biological processes. One hundred eleven genes (38 upregulated and 73 downregulated) were annotated by KO (KEGG Orthology) pathway mapping and involved metabolic pathways, biosynthesis of secondary metabolites and glycine, serine and threonine metabolism pathways. Validation of DEGs was performed, and the related gene expression levels showed a similar tendency to the DEG predictions at 4 d.p.i.; cell wall integrity and stress response component 1 (wsc1), cuticular protein and myo-inositol 2-dehydrogenase (iolG) were significantly upregulated, and small conductance calcium-activated potassium channel protein (SK) was significantly downregulated at 4 d.p.i. Related gene expression levels at different d.p.i. revealed that these DEGs were significantly regulated from the larval stage to the pupal stage, indicating the potential impacts of gene expression levels from the larval to the pupal stages. Taken together, DWV infection in the honey bee larval stage potentially influences the gene expression levels from larvae to pupae and reduces the survival rate of the pupal stage. This information emphasizes the consequences of DWV prevalence in honey bee larvae for apiculture.

miRNA Regulatory Functions in Farm Animal Diseases, and Biomarker Potentials for Effective Therapies.

MicroRNAs (miRNAs) are small endogenous RNAs that regulate gene expression post-transcriptionally by targeting either the 3' untranslated or coding regions of genes. They have been reported to play key roles in a wide range of biological processes. The recent remarkable developments of transcriptomics technologies, especially next-generation sequencing technologies and advanced bioinformatics tools, allow more in-depth exploration of messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs), including miRNAs. These technologies have offered great opportunities for a deeper exploration of miRNA involvement in farm animal diseases, as well as livestock productivity and welfare. In this review, we provide an overview of the current knowledge of miRNA roles in major farm animal diseases with a particular focus on diseases of economic importance. In addition, we discuss the steps and future perspectives of using miRNAs as biomarkers and molecular therapy for livestock disease management as well as the challenges and opportunities for understanding the regulatory mechanisms of miRNAs related to disease pathogenesis.

The role of a mechanistic host in maintaining arctic rabies variant distributions: Assessment of functional genetic diversity in Alaskan red fox (Vulpes vulpes).

Populations are exposed to different types and strains of pathogens across heterogeneous landscapes, where local interactions between host and pathogen may present reciprocal selective forces leading to correlated patterns of spatial genetic structure. Understanding these coevolutionary patterns provides insight into mechanisms of disease spread and maintenance. Arctic rabies (AR) is a lethal disease with viral variants that occupy distinct geographic distributions across North America and Europe. Red fox (Vulpes vulpes) are a highly susceptible AR host, whose range overlaps both geographically distinct AR strains and regions where AR is absent. It is unclear if genetic structure exists among red fox populations relative to the presence/absence of AR or the spatial distribution of AR variants. Acquiring these data may enhance our understanding of the role of red fox in AR maintenance/spread and inform disease control strategies. Using a genotyping-by-sequencing assay targeting 116 genomic regions of immunogenetic relevance, we screened for sequence variation among red fox populations from Alaska and an outgroup from Ontario, including areas with different AR variants, and regions where the disease was absent. Presumed neutral SNP data from the assay found negligible levels of neutral genetic structure among Alaskan populations. The immunogenetically-associated data identified 30 outlier SNPs supporting weak to moderate genetic structure between regions with and without AR in Alaska. The outliers included SNPs with the potential to cause missense mutations within several toll-like receptor genes that have been associated with AR outcome. In contrast, there was a lack of genetic structure between regions with different AR variants. Combined, we interpret these data to suggest red fox populations respond differently to the presence of AR, but not AR variants. This research increases our understanding of AR dynamics in the Arctic, where host/disease patterns are undergoing flux in a rapidly changing Arctic landscape, including the continued northward expansion of red fox into regions previously predominated by the arctic fox (Vulpes lagopus).

Sending Out Alarms: A Perspective on Intercellular Communications in Insect Antiviral Immune Response.

Viral infection triggers insect immune response, including RNA interference, apoptosis and autophagy, and profoundly changes the gene expression profiles in infected cells. Although intracellular degradation is crucial for restricting viral infection, intercellular communication is required to mount a robust systemic immune response. This review focuses on recent advances in understanding the intercellular communications in insect antiviral immunity, including protein-based and virus-derived RNA based cell-cell communications, with emphasis on the signaling pathway that induces the production of the potential cytokines. The prospects and challenges of future work are also discussed.

Genetic diversity of Bartonella species in small mammals in the Qaidam Basin, western China.

Investigation of the prevalence and diversity of Bartonella infections in small mammals in the Qaidam Basin, western China, could provide a scientific basis for the control and prevention of Bartonella infections in humans. Accordingly, in this study, small mammals were captured using snap traps in Wulan County and Ge'ermu City, Qaidam Basin, China. Spleen and brain tissues were collected and cultured to isolate Bartonella strains. The suspected positive colonies were detected with polymerase chain reaction amplification and sequencing of gltA, ftsZ, RNA polymerase beta subunit (rpoB) and ribC genes. Among 101 small mammals, 39 were positive for Bartonella, with the infection rate of 38.61%. The infection rate in different tissues (spleens and brains) (χ2 = 0.112, P = 0.738) and gender (χ2 = 1.927, P = 0.165) of small mammals did not have statistical difference, but that in different habitats had statistical difference (χ2 = 10.361, P = 0.016). Through genetic evolution analysis, 40 Bartonella strains were identified (two different Bartonella species were detected in one small mammal), including B. grahamii (30), B. jaculi (3), B. krasnovii (3) and Candidatus B. gerbillinarum (4), which showed rodent-specific characteristics. B. grahamii was the dominant epidemic strain (accounted for 75.0%). Furthermore, phylogenetic analysis showed that B. grahamii in the Qaidam Basin, might be close to the strains isolated from Japan and China. Overall, we observed a high prevalence of Bartonella infection in small mammals in the Qaidam Basin. B. grahamii may cause human disease, and the pathogenicity of the others Bartonella species needs further study, the corresponding prevention and control measures should be taken into consideration.

Integrated Analysis of mRNA-Seq and MiRNA-Seq Reveals the Molecular Mechanism of the Intestinal Immune Response in Marsupenaeus japonicus Under Decapod Iridescent Virus 1 Infection.

The intestine is not only an important digestive organ but also an important immune organ for shrimp; it plays a key role in maintaining homeostasis. Decapod iridescent virus 1 (DIV1) is a new type of shrimp-lethal virus that has received extensive attention in recent years. To date, most studies of the shrimp intestinal immune response under viral infections have relied on single omics analyses; there is a lack of systematic multi-omics research. In the current study, intestinal mRNA-seq and microRNA (miRNA)-seq analyses of Marsupenaeus japonicus under DIV1 infection were performed. A total of 1,976 differentially expressed genes (DEGs) and 32 differentially expressed miRNAs (DEMs) were identified. Among them, 21 DEMs were negatively correlated with 194 DEGs from a total of 223 correlations. Functional annotation analysis revealed that M. japonicus can regulate glycosaminoglycan biosynthesis (chondroitin sulfate, dermatan sulfate, and keratan sulfate), vitamin metabolism (retinol metabolism and ascorbate and aldarate metabolism), immune pathway activation (Toll and IMD signaling pathways, Wnt signaling pathway, IL-17 signaling pathway, and Hippo signaling pathway), immunity enzyme activity promotion (triose-phosphate isomerase), antimicrobial peptide (AMP) expression, reactive oxygen species (ROS) production, and cell apoptosis through miRNAs to participate in the host's antiviral immune response, while DIV1 can influence Warburg effect-related pathways (pyruvate metabolism, glycolysis/gluconeogenesis, and citrate cycle), glycosphingolipid biosynthesis-related pathways (glycosphingolipid biosynthesis-globo and isoglobo series and glycosphingolipid biosynthesis-lacto and neolacto series), and the tight junction and adhesion junction of the intestinal mucosal epithelium through the host's miRNAs and mRNA to promote its own invasion and replication. These results indicate that intestinal miRNAs play important roles in the shrimp immune response against DIV1 infection. This study provides a basis for further study of the shrimp intestinal antiviral immune response and for the formulation of effective new strategies for the prevention and treatment of DIV1 infection.

CD4, CD8b, and Cytokines Expression Profiles in Peripheral Blood Mononuclear Cells Infected with Different Subtypes of KoRV from Koalas (Phascolarctos cinereus) in a Japanese Zoo.

Koala retrovirus (KoRV) poses a major threat to koala health and conservation, and currently has 10 identified subtypes: an endogenous subtype (KoRV-A) and nine exogenous subtypes (KoRV-B to KoRV-J). However, subtype-related variations in koala immune response to KoRV are uncharacterized. In this study, we investigated KoRV-related immunophenotypic changes in a captive koala population (Hirakawa zoo, Japan) with a range of subtype infection profiles (KoRV-A only vs. KoRV-A with KoRV-B and/or -C), based on qPCR measurements of CD4, CD8b, IL-6, IL-10 and IL-17A mRNA expression in unstimulated and concanavalin (Con)-A-stimulated peripheral blood mononuclear cells (PBMCs). Although CD4, CD8b, and IL-17A expression did not differ between KoRV subtype infection profiles, IL-6 expression was higher in koalas with exogenous infections (both KoRV-B and KoRV-C) than those with the endogenous subtype only. IL-10 expression did not significantly differ between subtype infection profiles but did show a marked increase-accompanying decreased CD4:CD8b ratio-in a koala with lymphoma and co-infected with KoRV-A and -B, thus suggesting immunosuppression. Taken together, the findings of this study provide insights into koala immune response to multiple KoRV subtypes, which can be exploited for the development of prophylactic and therapeutic interventions for this iconic marsupial species.

Transcriptomic analysis of Procambarus clarkii affected by "Black May" disease.

Each year from April to May, high mortality rates are reported in red swamp crayfish (Procambarus clarkii) cultured in Jiangsu and other regions, in China, and this phenomenon has come to be known as "Black May" disease (BMD). Therefore, in order to investigate the possible causes of this disease, this study gathered BMD-affected P. clarkii samples and performed transcriptome analysis on hepatopancreas, gill, and muscle tissues. A total of 19,995,164, 149,212,804, and 222,053,848 clean reads were respectively obtained from the gills, muscle, and hepatopancreas of BMD-affected P. clarkii, and 114,024 unigenes were identified. The number of differentially expressed genes (DEGs) in gill, muscle, and hepatopancreas was 1703, 964, and 476, respectively. GO and KEGG enrichment analyses of the DEGs were then conducted. Based on KEGG pathway enrichment analysis, the most significantly differentially expressed pathways were mainly those involved with metabolism, human disease, and cellular processes. Further analysis of the significantly DEGs revealed that they were mainly related to the mitochondrial-mediated apoptosis pathway and that the expression of these DEGs was mostly down-regulated. Moreover, the expression of genes related to immune and metabolism-related pathways was also significantly down-regulated, and these significantly-inhibited pathways were the likely causes of P. clarkii death. Therefore, our results provide a basis for the identification of BMD causes.

Evolution and lineage dynamics of a transmissible cancer in Tasmanian devils.

Devil facial tumour 1 (DFT1) is a transmissible cancer clone endangering the Tasmanian devil. The expansion of DFT1 across Tasmania has been documented, but little is known of its evolutionary history. We analysed genomes of 648 DFT1 tumours collected throughout the disease range between 2003 and 2018. DFT1 diverged early into five clades, three spreading widely and two failing to persist. One clade has replaced others at several sites, and rates of DFT1 coinfection are high. DFT1 gradually accumulates copy number variants (CNVs), and its telomere lengths are short but constant. Recurrent CNVs reveal genes under positive selection, sites of genome instability, and repeated loss of a small derived chromosome. Cultured DFT1 cell lines have increased CNV frequency and undergo highly reproducible convergent evolution. Overall, DFT1 is a remarkably stable lineage whose genome illustrates how cancer cells adapt to diverse environments and persist in a parasitic niche.

Varroa destructor mites vector and transmit pathogenic honey bee viruses acquired from an artificial diet.

The ectoparasitic mite Varroa destructor is one of the most destructive pests of the honey bee (Apis mellifera) and the primary biotic cause of colony collapse in many regions of the world. These mites inflict physical injury on their honey bee hosts from feeding on host hemolymph and fat body cells/cellular components, and serve as the vector for deadly honey bee viruses, including Deformed wing virus (DWV) and the related Varroa destructor virus-1 (VDV-1) (i.e., DWV-like viruses). Studies focused on elucidating the dynamics of Varroa-mediated vectoring and transmission of DWV-like viruses may be confounded by viruses present in ingested host tissues or the mites themselves. Here we describe a system that includes an artificial diet free of insect tissue-derived components for maintaining Varroa mites for in vitro experimentation. Using this system, together with the novel engineered cDNA clone-derived genetically tagged VDV-1 and wild-type DWV, we demonstrated for the first time that Varroa mites provided an artificial diet supplemented with engineered viruses for 36 hours could acquire and transmit sufficient numbers of virus particles to establish an infection in virus-naïve hosts. While the in vitro system described herein provides for only up to five days of mite survival, precluding study of the long-term impacts of viruses on mite health, the system allows for extensive insights into the dynamics of Varroa-mediated vectoring and transmission of honey bee viruses.

Egg transcriptome profile responds to maternal virus infection in honey bees, Apis mellifera.

Trans-generational disease effects include vertical pathogen transmission but also immune priming to enhance offspring immunity. Accordingly, the survival consequences of maternal virus infection can vary and its molecular consequences during early development are poorly understood. The honey bee queen is long-lived and represents the central hub for vertical virus transmission as the sole reproductive individual in her colony. Even though virus symptoms in queens are mild, viral infection may have severe consequences for the offspring. Thus, transcriptome patterns during early developmental are predicted to respond to maternal virus infection. To test this hypothesis, gene expression patterns were compared among pooled honey bee eggs laid by queens that were either infected with Deformed wing virus (DWV1), Sacbrood virus (SBV2), both viruses (DWV and SBV), or no virus. Whole transcriptome analyses revealed significant expression differences of a few genes, some of which have hitherto no known function. Despite the paucity of single gene effects, functional enrichment analyses revealed numerous biological processes in the embryos to be affected by virus infection. Effects on several regulatory pathways were consistent with maternal responses to virus infection and correlated with responses to DWV and SBV in honey bee larvae and pupae. Overall, effects on egg transcriptome patterns were specific to each virus and the results of dual-infection samples suggested synergistic effects of DWV and SBV. We interpret our results as consequences of maternal infections. Thus, this first study to document and characterize virus-associated changes in the transcriptome of honey bee eggs represents an important contribution to understanding trans-generational virus effects, although more in-depth studies are needed to understand the detailed mechanisms of how viruses affect honey bee embryos.

A novel ß-catenin from Apostichopus japonicus mediates Vibrio splendidus-induced inflammatory-like response.

ß-catenin, an adaptor molecule in Wnt/ß-catenin signaling pathway, is associated with different physiological processes such as intestinal immune, apoptosis, and inflammation-associated response. However, the function of ß-catenin is still largely unknown in Apostichopus japonicus. In the present study, we cloned and characterized ß-catenin gene from A. japonicus by RNA-seq and RACE approaches. The complete sequence of Ajß-catenin consisted of a 5' UTR of 166 bp, a 3' UTR of 501 bp and an ORF of 2433 bp encoding a protein of 810 amino acids. Ajß-catenin has a GSK-ß consensus phosphorylation site of 21 amino acids located at N-terminal region and twelve Armadillo/ß-catenin-like repeat (ARM) domains from 145 to 671 aa. Spatial expression analysis revealed that Ajß-catenin mRNA levels displayed higher abundance in intestine. For Vibrio splendidus challenged sea cucumber, Ajß-catenin transcripts reached their peak at 6 h and remained at higher levels until 24 h post infection in comparison with that of the control group. GSK-3ß inhibitor treatment could induce both Ajß-catenin and the inflammatory factors expression. Ajß-catenin silencing could also down-regulate inflammatory factors expression. These results collectively suggested that Ajß-catenin was a novel molecule mediate V. splendidus-induced immune response of A. japonicus via regulating the inflammatory factors expression.

Trypanosomatid parasite dynamically changes the transcriptome during infection and modifies honey bee physiology.

It is still not understood how honey bee parasite changes the gene expression to adapt to the host environment and how the host simultaneously responds to the parasite infection by modifying its own gene expression. To address this question, we studied a trypanosomatid, Lotmaria passim, which can be cultured in medium and inhabit the honey bee hindgut. We found that L. passim decreases mRNAs associated with protein translation, glycolysis, detoxification of radical oxygen species, and kinetoplast respiratory chain to adapt to the anaerobic and nutritionally poor honey bee hindgut during the infection. After the long term infection, the host appears to be in poor nutritional status, indicated by the increase and decrease of take-out and vitellogenin mRNAs, respectively. Simultaneous gene expression profiling of L. passim and honey bee during infection by dual RNA-seq provided insight into how both parasite and host modify their gene expressions.

The economic value of R0 for selective breeding against microparasitic diseases.

BACKGROUND: Microparasitic diseases are caused by bacteria and viruses. Genetic improvement of resistance to microparasitic diseases in breeding programs is desirable and should aim at reducing the basic reproduction ratio [Formula: see text]. Recently, we developed a method to derive the economic value of [Formula: see text] for macroparasitic diseases. In epidemiological models for microparasitic diseases, an animal's disease status is treated as infected or not infected, resulting in a definition of [Formula: see text] that differs from that for macroparasitic diseases. Here, we extend the method for the derivation of the economic value of [Formula: see text] to microparasitic diseases. METHODS: When [Formula: see text], the economic value of [Formula: see text] is zero because the disease is very rare. When [Formula: see text]. is higher than 1, genetic improvement of [Formula: see text] can reduce expenditures on vaccination if vaccination induces herd immunity, or it can reduce production losses due to disease. When vaccination is used to achieve herd immunity, expenditures are proportional to the critical vaccination coverage, which decreases with [Formula: see text]. The effect of [Formula: see text] on losses is considered separately for epidemic and endemic disease. Losses for epidemic diseases are proportional to the probability and size of major epidemics. Losses for endemic diseases are proportional to the infected fraction of the population at the endemic equilibrium. RESULTS: When genetic improvement reduces expenditures on vaccination, expenditures decrease with [Formula: see text] at an increasing rate. When genetic improvement reduces losses in epidemic or endemic diseases, losses decrease with [Formula: see text] at an increasing rate. Hence, in all cases, the economic value of [Formula: see text] increases as [Formula: see text] decreases towards 1. DISCUSSION: [Formula: see text] and its economic value are more informative for potential benefits of genetic improvement than heritability estimates for survival after a disease challenge. In livestock, the potential for genetic improvement is small for epidemic microparasitic diseases, where disease control measures limit possibilities for phenotyping. This is not an issue in aquaculture, where controlled challenge tests are performed in dedicated facilities. If genetic evaluations include infectivity, genetic gain in [Formula: see text] can be accelerated but this would require different testing designs. CONCLUSIONS: When [Formula: see text], its economic value is zero. The economic value of [Formula: see text] is highest at low values of [Formula: see text] and approaches zero at high values of [Formula: see text].

The Enhanced Immune Protection in Chinese Mitten Crab Eriocheir sinensis Against the Second Exposure to Bacteria Aeromonas hydrophila.

Accumulating evidences suggest that the enhanced immune responses and increased protection against bacteria-induced mortality can be initiated after the primary exposure to various microbial communities and their components in various organisms including commercially valuable crustaceans. In the present study, the survival rate and immune responses of Chinese mitten crab Eriocheir sinensis were determined after an immune priming (IP) with formalin-killed Aeromonas hydrophila and an immune challenge (ICH) with the same but live pathogen (Ah group). A group in which the animals received a salt injection prior to challenge was maintained as control (Ns group). In the present study, it was shown that an IP with killed A. hydrophila can significantly protect the crabs against the ICH with a lethal dose of the live pathogen. The increased survival was associated with elevated rate and duration of phagocytosis. The antibacterial activity of the serum was significantly increased in Ah group compared to that in Ns group. Significant changes of phenoloxidase (PO) activities were also found between Ah and Ns group but not in Ah group between IP and ICH. No significant changes of lysozyme were found in Ah and NS group during the whole experiment except 3 h after IP. In addition, the levels of transcripts and protein of Dscam were increased in hemocytes of the crabs from Ah group. All the results suggested that a primary immune priming with a particular killed pathogen could induce an enhanced immunity in crabs when they were encountered secondly with the same live pathogen. The evidences of elevated immune protections in crabs would contribute to better understand the mechanism of immune priming in invertebrates.

A feline orthologue of the human MYH7 c.5647G>A (p.(Glu1883Lys)) variant causes hypertrophic cardiomyopathy in a Domestic Shorthair cat.

Hypertrophic cardiomyopathy (HCM) is the most common inherited human heart disease. The same disease has a high prevalence in cats, where it is also suspected to be inherited. More than 1500 variants in MYBPC3, MYH7 and other sarcomeric genes are associated with human HCM, while in cats, only two causative variants in MYBPC3 are currently known. Here, we describe an adult Domestic Shorthair cat with arterial thromboembolism and heart failure that was diagnosed with HCM on necropsy. Sequencing of the coding regions of MYBPC3 and MYH7 revealed 21 variants, of which the MYH7 c.5647G>A (p.(Glu1883Lys)) variant was further analysed, because its orthologous variant had already been reported in a human patient with HCM, but with limited causal evidence. This variant affects the highly conserved assembly competence domain, is predicted in silico to be damaging and was found only once in population databases. Recently, functional studies have confirmed its predicted damaging effect and a paralogous variant in MYH6 has been associated with cardiac disease in humans as well. This report of an orthologous variant in a cat with HCM and its absence in 200 additional cats provides further evidence for its disease-causing nature. As the first report of feline HCM caused by a variant in MYH7, this study also emphasises this gene as a candidate gene for future studies in cats and highlights the similarity between human and feline HCM.