Genome-wide association study reveals novel candidate genes for litter size in Markhoz goats

IntroductionThe Markhoz goat is the only breed that can produce high-quality fiber called mohair in Iran; however, the size of its population has faced a dramatic decline during the last decades, mainly due to the reluctance of farmers to rear Markhoz goats caused by a reduction in goat production income. Litter size at birth (LSB) and weaning (LSW) are two economically important reproductive traits for local goat breeders and have the potential of increasing the population growth rate. The present study was aimed to identify possible genomic regions that are associated with LSB and LSW in Markhoz goats using a genome-wide association study (GWAS). MethodsTo this end, 136 Markhoz goats with record(s) of kidding were selected for GWAS using the Illumina Caprine 50K bead chip. The individual breeding values (BV) of available LSB and LSW records estimated under an animal mixed model were used as the dependent variable in the GWAS, thereby incorporating repeated categorical variables of litter size. ResultsFour SNPs on chromosomes 2, 20 and 21 were identified to be significantly associated (FDR p < 0.05) with LSB after multiple testing correction under a Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK) model. Least-square analysis was performed to investigate the effects of detected genotypes on LSB. Ultimately, the GWAS results introduced six candidate genes, including GABRA5, AKAP13, SV2B, PPP1R1C, SSFA2 and TRNAS-GCU in a 100 kb adjacent region of the identified SNPs. Previous studies proposed functional roles of GABRA5 and AKAP13 genes in reproductive processes; however, the role of other candidate genes in reproduction is not clear. ConclusionThese findings warrant further investigation for use in marker-assisted selection programs in Markhoz goats

Engaging older adults in healthcare research and planning: a realist synthesis

Background The importance of engaging the community in healthcare research and planning has been widely recognized. Currently however, there is a limited focus on older adults, Canada’s fastest growing segment of the population and biggest users of the healthcare system. Objective This project aimed to develop an understanding of engagement of older adults and their caregivers in healthcare research and planning. Method A realist synthesis was conducted of the available knowledge on engagement in healthcare research and planning. The search methodology was informed by a framework for realist syntheses following five phases, including consultations with older adults. The synthesis included theoretical frameworks, and both peer-reviewed and grey literature. Results The search generated 15,683 articles, with 562 focusing on healthcare research and planning. The review lead to the development of a framework to engage older adults and their caregivers in healthcare research and planning. The 5 stages environment, plan, establish, build, and transition are accompanied with example context, mechanism, and outcomes to guide the use of this framework. Conclusion We have identified a framework that promotes meaningful engagement of older adults and their caregivers. We are continuing to collaborate with our community partners to further develop and evaluate engagement strategies that align with the presented framework.This work was supported by a Knowledge Synthesis Grant from the Technology Evaluation for the Elderly Network (TVN), grant # KS2013-08, which is funded by the Government of Canada’s Networks of Centres of Excellence (NCE) Program

The systemic inflammatory response to exercise in adults with cystic fibrosis

AbstractExercise is associated with release of inflammatory mediators in the circulation and there is evidence that the exercising muscles and tendons are sources of interleukin-6. Due to the catabolic effects of some cytokines, increased release in circulation might contribute to alterations in body composition in adults with cystic fibrosis. We hypothesised that exercise of moderate intensity would generate increased blood concentrations of some inflammatory mediators.We investigated the change in blood concentrations of interleukin-6, tumour necrosis factor alpha and their soluble receptors after a structured exercise (box stepping) of intensity similar to that encountered during activities of daily living in 12 adults with cystic fibrosis and mean (95% confidence interval) FEV1 55.6 (44.4, 66.8)% predicted, body mass index 23.0 (21.3, 24.6) kg/m2 and 12 healthy subjects.The increments post-exercise for all inflammatory mediators and lactate corrected for the work performed until voluntary exhaustion were greater for patients, while the total work was less for patients (all p<0.01). Daytime variability of the inflammatory mediators was assessed in eight patients and was less than the change due to exercise.We report greater increments in circulating concentrations of some cytokines with moderate exercise in adults with cystic fibrosis compared to healthy subjects

Genome-wide SNPs analysis of indigenous Zebu breeds in Pakistan

Prospects of high throughput technology in animal genetics makes easy to investigate hidden genetic variation in farm animal's genetic resources. However, many SNPs technologies are currently practicing in animal genetics. In this study, we investigated genome wide SNPs variations and its distribution across the indigenous cattle population in Pakistan using Illumina Bovine HD (777K) SNPs bead chip. A total of 136 individuals from ten different breeds were genotyped and after filtration 500, 939 SNPs markers were used for further analysis. The mean minor allele frequency (MAF) was 0.23, 0.20, 0.22, 0.22, 0.20, 0.18, 0.20, 0.22, 0.21 and 0.18 observed for Achi, Bhagnari, Cholistani, Dhanni, Dajal, Kankraj, Lohani, Red sindi, Sahiwal and Tharparkar cattle, respectively. Significant difference (P0.05) within breeds and remaining 36% were considered as monomorphic markers. Average observed (Ho) and expected (HE) heterozygosity values 0.662 and 0.640 were estimated among these breeds. In conclusion, this preliminary study results revealed that these SNPs variation level could potentially be used for genetic characterization of zebu cattle breeds and could also be used to estimate genetic potential of these cattle breeds for livestock improvement in country

Surface molecules of extracellular vesicles secreted by the helminth pathogen Fasciola hepatica direct their internalisation by host cells.

<div><p>Helminth parasites secrete extracellular vesicles (EVs) that can be internalised by host immune cells resulting in modulation of host immunity. While the molecular cargo of EVs have been characterised in many parasites, little is known about the surface-exposed molecules that participate in ligand-receptor interactions with the host cell surface to initiate vesicle docking and subsequent internalisation. Using a membrane-impermeable biotin reagent to capture proteins displayed on the outer membrane surface of two EV sub-populations (termed 15k and 120k EVs) released by adult <i>F</i>. <i>hepatica</i>, we describe 380 surface proteins including an array of virulence factors, membrane transport proteins and molecules involved in EV biogenesis/trafficking. Proteomics and immunohistochemical analysis show that the 120k EVs have an endosomal origin and may be released from the parasite via the protonephridial (excretory) system whilst the larger 15k EVs are released from the gastrodermal epithelial cells that line the fluke gut. A parallel lectin microarray strategy was used to profile the topology of major surface oligosaccharides of intact fluorogenically-labelled EVs as they would be displayed to the host. Lectin profiles corresponding to glycoconjugates exposed on the surface of the 15 K and 120K EV sub-populations are practically identical but are distinct from those of the parasite surface tegument, although all are predominated by high mannose sugars. We found that while the <i>F</i>. <i>hepatica</i> EVs were resistant to <i>exo</i>- and <i>endo</i>-glycosidases, the glyco-amidase PNGase F drastically remodelled the surface oligosaccharides and blocked the uptake of EVs by host macrophages. In contrast, pre-treatment with antibodies obtained from infected hosts, or purified antibodies raised against the extracellular domains of specific EV surface proteins (DM9-containing protein, CD63 receptor and myoferlin), significantly enhanced their cellular internalisation. This work highlights the diversity of EV biogenesis and trafficking pathways used by <i>F</i>. <i>hepatica</i> and sheds light on the molecular interaction between parasite EVs and host cells.</p></div

Combining landscape genomics and ecological modelling to investigate local adaptation of indigenous Ugandan cattle to East Coast fever

East Coast fever (ECF) is a fatal sickness affecting cattle populations of eastern, central, and southern Africa. The disease is transmitted by the tick Rhipicephalus appendiculatus, and caused by the protozoan Theileria parva parva, which invades host lymphocytes and promotes their clonal expansion. Importantly, indigenous cattle show tolerance to infection in ECF-endemically stable areas. Here, the putative genetic bases underlying ECF-tolerance were investigated using molecular data and epidemiological information from 823 indigenous cattle from Uganda. Vector distribution and host infection risk were estimated over the study area and subsequently tested as triggers of local adaptation by means of landscape genomics analysis. We identified 41 and seven candidate adaptive loci for tick resistance and infection tolerance, respectively. Among the genes associated with the candidate adaptive loci are PRKG1 and SLA2. PRKG1 was already described as associated with tick resistance in indigenous South African cattle, due to its role into inflammatory response. SLA2 is part of the regulatory pathways involved into lymphocytes' proliferation. Additionally, local ancestry analysis suggested the zebuine origin of the genomic region candidate for tick resistance

Genome-Wide Association Analysis Identifies a Mutation in the Thiamine Transporter 2 (SLC19A3) Gene Associated with Alaskan Husky Encephalopathy

Alaskan Husky Encephalopathy (AHE) has been previously proposed as a mitochondrial encephalopathy based on neuropathological similarities with human Leigh Syndrome (LS). We studied 11 Alaskan Husky dogs with AHE, but found no abnormalities in respiratory chain enzyme activities in muscle and liver, or mutations in mitochondrial or nuclear genes that cause LS in people. A genome wide association study was performed using eight of the affected dogs and 20 related but unaffected control AHs using the Illumina canine HD array. SLC19A3 was identified as a positional candidate gene. This gene controls the uptake of thiamine in the CNS via expression of the thiamine transporter protein THTR2. Dogs have two copies of this gene located within the candidate interval (SLC19A3.2 – 43.36–43.38 Mb and SLC19A3.1 – 43.411–43.419 Mb) on chromosome 25. Expression analysis in a normal dog revealed that one of the paralogs, SLC19A3.1, was expressed in the brain and spinal cord while the other was not. Subsequent exon sequencing of SLC19A3.1 revealed a 4bp insertion and SNP in the second exon that is predicted to result in a functional protein truncation of 279 amino acids (c.624 insTTGC, c.625 C>A). All dogs with AHE were homozygous for this mutation, 15/41 healthy AH control dogs were heterozygous carriers while 26/41 normal healthy AH dogs were wild type. Furthermore, this mutation was not detected in another 187 dogs of different breeds. These results suggest that this mutation in SLC19A3.1, encoding a thiamine transporter protein, plays a critical role in the pathogenesis of AHE.University of California, Davis. School of Veterinary Medicine. Center for Companion Animal Healt

AdaptMap: exploring goat diversity and adaptation

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Using the community-based breeding program (CBBP) model as a collaborative platform to develop the African Goat Improvement Network—Image collection protocol (AGIN-ICP) with mobile technology for data collection and management of livestock phenotypes

Introduction: The African Goat Improvement Network Image Collection Protocol (AGIN-ICP) is an accessible, easy to use, low-cost procedure to collect phenotypic data via digital images. The AGIN-ICP collects images to extract several phenotype measures including health status indicators (anemia status, age, and weight), body measurements, shapes, and coat color and pattern, from digital images taken with standard digital cameras or mobile devices. This strategy is to quickly survey, record, assess, analyze, and store these data for use in a wide variety of production and sampling conditions.Methods: The work was accomplished as part of the multinational African Goat Improvement Network (AGIN) collaborative and is presented here as a case study in the AGIN collaboration model and working directly with community-based breeding programs (CBBP). It was iteratively developed and tested over 3 years, in 12 countries with over 12,000 images taken.Results and discussion: The AGIN-ICP development is described, and field implementation and the quality of the resulting images for use in image analysis and phenotypic data extraction are iteratively assessed. Digital body measures were validated using the PreciseEdge Image Segmentation Algorithm (PE-ISA) and software showing strong manual to digital body measure Pearson correlation coefficients of height, length, and girth measures (0.931, 0.943, 0.893) respectively. It is critical to note that while none of the very detailed tasks in the AGIN-ICP described here is difficult, every single one of them is even easier to accidentally omit, and the impact of such a mistake could render a sample image, a sampling day’s images, or even an entire sampling trip’s images difficult or unusable for extracting digital phenotypes. Coupled with tissue sampling and genomic testing, it may be useful in the effort to identify and conserve important animal genetic resources and in CBBP genetic improvement programs by providing reliably measured phenotypes with modest cost. Potential users include farmers, animal husbandry officials, veterinarians, regional government or other public health officials, researchers, and others. Based on these results, a final AGIN-ICP is presented, optimizing the costs, ease, and speed of field implementation of the collection method without compromising the quality of the image data collection