Genetic effects on coat colour in cattle: dilution of eumelanin and phaeomelanin pigments in an F2-Backcross Charolais × Holstein population

<p>Abstract</p> <p>Background</p> <p>In cattle, the gene coding for the melanocortin receptor 1 (<it>MC1R</it>) is known to be the main regulator of the switch between the two coat colour pigments: eumelanin (black pigment) and phaeomelanin (red pigment). Some breeds, such as Charolais and Simmental, exhibit a lightening of the original pigment over the whole body. The dilution mutation in Charolais (<it>Dc</it>) is responsible for the white coat colour of this breed. Using an F2-Backcross Charolais × Holstein population which includes animals with both pigment backgrounds, we present a linkage mapping study of the Charolais dilution locus.</p> <p>Results</p> <p>A Charolais × Holstein crossbred population was investigated for genetic effects on coat colour dilution. Three different traits representing the dilution of the phaeomelanin, eumelanin, and non-pigment-specific dilution were defined. Highly significant genome-wide associations were detected on chromosome 5 for the three traits analysed in the marker interval [ETH10-DIK5248]. The <it>SILV </it>gene was examined as the strongest positional and functional candidate gene. A previously reported non-synonymous mutation in exon 1 of this gene, <it>SILV </it>c.64A>G, was associated with the coat colour dilution phenotype in this resource population. Although some discrepancies were identified between this mutation and the dilution phenotype, no convincing recombination events were found between the <it>SILV </it>c.64A>G mutation and the <it>Dc </it>locus. Further analysis identified a region on chromosome 28 influencing the variation in pigment intensity for a given coat colour category.</p> <p>Conclusion</p> <p>The present study has identified a region on bovine chromosome 5 that harbours the major locus responsible for the dilution of the eumelanin and phaeomelanin seen in Charolais crossbred cattle. In this study, no convincing evidence was found to exclude <it>SILV </it>c.64A>G as the causative mutation for the Charolais dilution phenotype, although other genetic effects may influence the coat colour variation in the population studied. A region on chromosome 28 influences the intensity of pigment within coat colour categories, and therefore may include a modifier of the <it>Dc </it>locus. A candidate gene for this effect, <it>LYST</it>, was identified.</p

Unravelling selection signatures in a single dog breed suggests recent selection for morphological and behavioral traits

Strong selection has resulted in substantial morphological and behavioral diversity across modern dog breeds, which makes dogs interesting model animals to study the underlying genetic architecture of these traits. However, results from between-breed analyses may confound selection signatures for behavior and morphological features that were coselected during breed development. In this study, we assess population genetic differences in a unique resource of dogs of the same breed but with systematic behavioral selection in only one population. We exploit these different breeding backgrounds to identify signatures of recent selection. Selection signatures within populations were found on chromosomes 4 and 19, with the strongest signals in behavior-related genes. Regions showing strong signals of divergent selection were located on chromosomes 1, 24, and 32, and include candidate genes for both physical features and behavior. Some of the selection signatures appear to be driven by loci associated with coat color (Chr 24; ASIP) and length (Chr 32; FGF5), while others showed evidence of association with behavior. Our findings suggest that signatures of selection within dog breeds have been driven by selection for morphology and behavior. Furthermore, we demonstrate that combining selection scans with association analyses is effective for dissecting the traits under selection

Muscle-related traits in cattle: The role of the myostatin gene in the South Devon breed

In this paper, we examined the effects of an 11-bp mutation within the GDF-8 gene, originally identified in Belgian Blue cattle, in the South Devon breed. The mutation was found at moderate frequency (0.37) in the South Devon population. We quantified the effects of this mutation on growth, body composition and calving traits in South Devon cattle. We found that the mutation significantly increased muscle score and calving difficulty and decreased fat depth. The mutation did not significantly affect weight at 200 and 400 days or muscle depth. Its effect on muscle score and fat depth was additive while its effect on calving difficulty was recessive. The mutation accounted for a significant proportion of the phenotypic variance in muscle score and calving difficulty. There was an economic benefit of the mutation for this data set, however, calculations were sensitive to changes in the parameter values. Additional data would be required to refine these calculations

Evaluation of approaches for identifying population informative markers from high density SNP Chips

<p>Abstract</p> <p>Background</p> <p>Genetic markers can be used to identify and verify the origin of individuals. Motivation for the inference of ancestry ranges from conservation genetics to forensic analysis. High density assays featuring Single Nucleotide Polymorphism (SNP) markers can be exploited to create a reduced panel containing the most informative markers for these purposes. The objectives of this study were to evaluate methods of marker selection and determine the minimum number of markers from the BovineSNP50 BeadChip required to verify the origin of individuals in European cattle breeds. Delta, Wright's F_ST, Weir & Cockerham's F_STand PCA methods for population differentiation were compared. The level of informativeness of each SNP was estimated from the breed specific allele frequencies. Individual assignment analysis was performed using the ranked informative markers. Stringency levels were applied by log-likelihood ratio to assess the confidence of the assignment test.</p> <p>Results</p> <p>A 95% assignment success rate for the 384 individually genotyped animals was achieved with < 80, < 100, < 140 and < 200 SNP markers (with increasing stringency threshold levels) across all the examined methods for marker selection. No further gain in power of assignment was achieved by sampling in excess of 200 SNP markers. The marker selection method that required the lowest number of SNP markers to verify the animal's breed origin was Wright's F_ST(60 to 140 SNPs depending on the chosen degree of confidence). Certain breeds required fewer markers (< 100) to achieve 100% assignment success. In contrast, closely related breeds require more markers (~200) to achieve > 95% assignment success. The power of assignment success, and therefore the number of SNP markers required, is dependent on the levels of genetic heterogeneity and pool of samples considered.</p> <p>Conclusions</p> <p>While all SNP selection methods produced marker panels capable of breed identification, the power of assignment varied markedly among analysis methods. Thus, with effective exploration of available high density genetic markers, a diagnostic panel of highly informative markers can be produced.</p

Joint genomic prediction of canine hip dysplasia in UK and US Labrador Retrievers

Canine hip dysplasia, a debilitating orthopedic disorder that leads to osteoarthritis and cartilage degeneration, is common in several large-sized dog breeds and shows moderate heritability suggesting that selection can reduce prevalence. Estimating genomic breeding values require large reference populations, which are expensive to genotype for development of genomic prediction tools. Combining datasets from different countries could be an option to help build larger reference datasets without incurring extra genotyping costs. Our objective was to evaluate genomic prediction based on a combination of UK and US datasets of genotyped dogs with records of Norberg angle scores, related to canine hip dysplasia. Prediction accuracies using a single population were 0.179 and 0.290 for 1,179 and 242 UK and US Labrador Retrievers, respectively. Prediction accuracies changed to 0.189 and 0.260, with an increased bias of genomic breeding values when using a joint training set (biased upwards for the US population and downwards for the UK population). Our results show that in this study of canine hip dysplasia, little or no benefit was gained from using a joint training set as compared to using a single population as training set. We attribute this to differences in the genetic background of the two populations as well as the small sample size of the US dataset

Development of a genetic tool for product regulation in the diverse British pig breed market

<p>Abstract</p> <p>Background</p> <p>The application of DNA markers for the identification of biological samples from both human and non-human species is widespread and includes use in food authentication. In the food industry the financial incentive to substituting the true name of a food product with a higher value alternative is driving food fraud. This applies to British pork products where products derived from traditional pig breeds are of premium value. The objective of this study was to develop a genetic assay for regulatory authentication of traditional pig breed-labelled products in the porcine food industry in the United Kingdom.</p> <p>Results</p> <p>The dataset comprised of a comprehensive coverage of breed types present in Britain: 460 individuals from 7 traditional breeds, 5 commercial purebreds, 1 imported European breed and 1 imported Asian breed were genotyped using the PorcineSNP60 beadchip. Following breed-informative SNP selection, assignment power was calculated for increasing SNP panel size. A 96-plex assay created using the most informative SNPs revealed remarkably high genetic differentiation between the British pig breeds, with an average F_ST of 0.54 and Bayesian clustering analysis also indicated that they were distinct homogenous populations. The posterior probability of assignment of any individual of a presumed origin actually originating from that breed given an alternative breed origin was > 99.5% in 174 out of 182 contrasts, at a test value of log(LR) > 0. Validation of the 96-plex assay using independent test samples of known origin was successful; a subsequent survey of market samples revealed a high level of breed label conformity.</p> <p>Conclusion</p> <p>The newly created 96-plex assay using selected markers from the PorcineSNP60 beadchip enables powerful assignment of samples to traditional breed origin and can effectively identify mislabelling, providing a highly effective tool for DNA analysis in food forensics.</p

Quantitative trait loci mapping for canine hip dysplasia and its related traits in UK Labrador Retrievers

BACKGROUND: Canine hip dysplasia (CHD) is characterised by a malformation of the hip joint, leading to osteoarthritis and lameness. Current breeding schemes against CHD have resulted in measurable but moderate responses. The application of marker-assisted selection, incorporating specific markers associated with the disease, or genomic selection, incorporating genome-wide markers, has the potential to dramatically improve results of breeding schemes. Our aims were to identify regions associated with hip dysplasia or its related traits using genome and chromosome-wide analysis, study the linkage disequilibrium (LD) in these regions and provide plausible gene candidates. This study is focused on the UK Labrador Retriever population, which has a high prevalence of the disease and participates in a recording program led by the British Veterinary Association (BVA) and The Kennel Club (KC). RESULTS: Two genome-wide and several chromosome-wide QTLs affecting CHD and its related traits were identified, indicating regions related to hip dysplasia. CONCLUSION: Consistent with previous studies, the genetic architecture of CHD appears to be based on many genes with small or moderate effect, suggesting that genomic selection rather than marker-assisted selection may be an appropriate strategy for reducing this disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-833) contains supplementary material, which is available to authorized users

The Benefits and Burdens of Pediatric Palliative Care and End-of-Life Research: A Systematic Review

Objective: The aim of this study is to report the benefits and burdens of palliative research participation on children, siblings, parents, clinicians, and researchers. Background: Pediatric palliative care requires research to mature the science and improve interventions. A tension exists between the desire to enhance palliative and end-of-life care for children and their families and the need to protect these potentially vulnerable populations from untoward burdens. Methods: Systematic review followed PRISMA guidelines with prepared protocol registered as PROSPERO #CRD42018087304. MEDLINE, CINAHL, PsycINFO, EMBASE, Scopus, and The Cochrane Library were searched (2000–2017). English-language studies depicting the benefits or burdens of palliative care or end-of-life research participation on either pediatric patients and/or their family members, clinicians, or study teams were eligible for inclusion. Study quality was appraised using the Mixed Methods Appraisal Tool (MMAT). Results: Twenty-four studies met final inclusion criteria. The benefit or burden of palliative care research participation was reported for the child in 6 papers; siblings in 2; parents in 19; clinicians in 3; and researchers in 5 papers. Benefits were more heavily emphasized by patients and family members, whereas burdens were more prominently emphasized by researchers and clinicians. No paper utilized a validated benefit/burden scale. Discussion: The lack of published exploration into the benefits and burdens of those asked to take part in pediatric palliative care research and those conducting the research is striking. There is a need for implementation of a validated benefit/burden instrument or interview measure as part of pediatric palliative and end-of-life research design and reporting

Mapping restricted introgression across the genomes of admixed indigenous African cattle breeds

Background: The genomes of indigenous African cattle are composed of components with Middle Eastern (taurine) and South Asian (indicine) origins, providing a valuable model to study hybridization and to identify genetic barriers to gene flow. In this study, we analysed indigenous African cattle breeds as models of hybrid zones, considering taurine and indicine samples as ancestors. In a genomic cline analysis of whole-genome sequence data, we considered over 8 million variants from 144 animals, which allows for fine-mapping of potential genomic incompatibilities at high resolution across the genome. Results: We identified several thousand variants that had significantly steep clines (‘SCV’) across the whole genome, indicating restricted introgression. Some of the SCV were clustered into extended regions, with the longest on chromosome 7, spanning 725 kb and including 27 genes. We found that variants with a high phenotypic impact (e.g. indels, intra-genic and missense variants) likely represent greater genetic barriers to gene flow. Furthermore, our findings provide evidence that a large proportion of breed differentiation in African cattle could be linked to genomic incompatibilities and reproductive isolation. Functional evaluation of genes with SCV suggest that mitonuclear incompatibilities and genes associated with fitness (e.g. resistance to paratuberculosis) could account for restricted gene flow in indigenous African cattle. Conclusions: To our knowledge, this is the first time genomic cline analysis has been applied to identify restricted introgression in the genomes of indigenous African cattle and the results provide extended insights into mechanisms (e.g. genomic incompatibilities) contributing to hybrid differentiation. These results have important implications for our understanding of genetic incompatibilities and reproductive isolation and provide important insights into the impact of cross-breeding cattle with the aim of producing offspring that are both hardy and productive