BMC genomics.
Publisher:
BioMed Central,
Country: England
Language: English
Start Year:2000 -
ISSN:
1471-2164 (Electronic)
1471-2164 (Linking)
1471-2164 (Linking)
Impact Factor
4.4
2022
| NLM ID: | 100965258 |
| (OCoLC): | 45259143 |
| LCCN: | 2002243071 |
Genome data uncover four synergistic key regulators for extremely small body size in horses. Miniature size in horses represents an extreme reduction of withers height that originated after domestication. In some breeds, it is a highly desired trait representing a breed- or subtype-specific feature. The genomic changes that emerged due to strong-targeted selection towards this distinct type remain unclear. Results: Comparisons of whole-genome sequencing data from two Miniature Shetland ponies and one standard-sized Shetland pony, performed to elucidate genetic determinants for miniature size, revealed four synergistic variants, limiting withers height to 34.25 in. (87 cm). Runs of h...
Impaired response of the bronchial epithelium to inflammation characterizes severe equine asthma. Severe equine asthma is a naturally occurring lung inflammatory disease of mature animals characterized by neutrophilic inflammation, bronchoconstriction, mucus hypersecretion and airway remodeling. Exacerbations are triggered by inhalation of dust and microbial components. Affected animals eventually are unable of aerobic performance. In this study transcriptomic differences between asthmatic and non-asthmatic animals in the response of the bronchial epithelium to an inhaled challenge were determined. Results: Paired endobronchial biopsies were obtained pre- and post-challenge from asthmatic ...
Genetic and codon usage bias analyses of polymerase genes of equine influenza virus and its relation to evolution. Equine influenza is a major health problem of equines worldwide. The polymerase genes of influenza virus have key roles in virus replication, transcription, transmission between hosts and pathogenesis. Hence, the comprehensive genetic and codon usage bias of polymerase genes of equine influenza virus (EIV) were analyzed to elucidate the genetic and evolutionary relationships in a novel perspective. Results: The group - specific consensus amino acid substitutions were identified in all polymerase genes of EIVs that led to divergence of EIVs into various clades. The consistent amino acid changes...
Equine skeletal muscle adaptations to exercise and training: evidence of differential regulation of autophagosomal and mitochondrial components. A single bout of exercise induces changes in gene expression in skeletal muscle. Regular exercise results in an adaptive response involving changes in muscle architecture and biochemistry, and is an effective way to manage and prevent common human diseases such as obesity, cardiovascular disorders and type II diabetes. However, the biomolecular mechanisms underlying such responses still need to be fully elucidated. Here we performed a transcriptome-wide analysis of skeletal muscle tissue in a large cohort of untrained Thoroughbred horses (n = 51) before and after a bout of high-intensity exe...
Developing a 670k genotyping array to tag ~2M SNPs across 24 horse breeds. To date, genome-scale analyses in the domestic horse have been limited by suboptimal single nucleotide polymorphism (SNP) density and uneven genomic coverage of the current SNP genotyping arrays. The recent availability of whole genome sequences has created the opportunity to develop a next generation, high-density equine SNP array. Using whole genome sequence from 153 individuals representing 24 distinct breeds collated by the equine genomics community, we cataloged over 23 million de novo discovered genetic variants. Leveraging genotype data from individuals with both whole genome sequence, ...
Identification of long non-coding RNA in the horse transcriptome. Efforts to resolve the transcribed sequences in the equine genome have focused on protein-coding RNA. The transcription of the intergenic regions, although detected via total RNA sequencing (RNA-seq), has yet to be characterized in the horse. The most recent equine transcriptome based on RNA-seq from several tissues was a prime opportunity to obtain a concurrent long non-coding RNA (lncRNA) database. This lncRNA database has a breadth of eight tissues and a depth of over 20 million reads for select tissues, providing the deepest and most expansive equine lncRNA database. Utilizing the intergen...
Defining the ABC of gene essentiality in streptococci. Utilising next generation sequencing to interrogate saturated bacterial mutant libraries provides unprecedented information for the assignment of genome-wide gene essentiality. Exposure of saturated mutant libraries to specific conditions and subsequent sequencing can be exploited to uncover gene essentiality relevant to the condition. Here we present a barcoded transposon directed insertion-site sequencing (TraDIS) system to define an essential gene list for Streptococcus equi subsp. equi, the causative agent of strangles in horses, for the first time. The gene essentiality data for this grou...
Understanding the response to endurance exercise using a systems biology approach: combining blood metabolomics, transcriptomics and miRNomics in horses. Endurance exercise in horses requires adaptive processes involving physiological, biochemical, and cognitive-behavioral responses in an attempt to regain homeostasis. We hypothesized that the identification of the relationships between blood metabolome, transcriptome, and miRNome during endurance exercise in horses could provide significant insights into the molecular response to endurance exercise. For this reason, the serum metabolome and whole-blood transcriptome and miRNome data were obtained from ten horses before and after a 160 km endurance competition. We obtained a global regulatory ...
Tissue resolved, gene structure refined equine transcriptome. Transcriptome interpretation relies on a good-quality reference transcriptome for accurate quantification of gene expression as well as functional analysis of genetic variants. The current annotation of the horse genome lacks the specificity and sensitivity necessary to assess gene expression especially at the isoform level, and suffers from insufficient annotation of untranslated regions (UTR) usage. We built an annotation pipeline for horse and used it to integrate 1.9 billion reads from multiple RNA-seq data sets into a new refined transcriptome. This equine transcriptome integrates eight d...
LPS-induced modules of co-expressed genes in equine peripheral blood mononuclear cells. Lipopolysaccharide (endotoxin, LPS) is a strong inducer of the innate immune response. It is widespread in our environment, e.g. in house dust and contributes to asthma. Compared to humans, horses are even more sensitive to LPS. However, data on LPS effects on the equine transcriptome are very limited. Using RNA-seq we analysed LPS-induced differences in the gene expression in equine peripheral blood mononuclear cells at the gene and gene-network level in two half-sib families and one group of unrelated horses. 24 h-LPS challenge of equine immune cells resulted in substantial changes in the t...
TRPM2 SNP genotype previously associated with susceptibility to Rhodococcus equi pneumonia in Quarter Horse foals displays differential gene expression identified using RNA-Seq. Rhodococcus equi (R. equi) is an intracellular bacterium that affects young foals and immuno-compromised individuals causing severe pneumonia. Currently, the genetic mechanisms that confer susceptibility and/or resistance to R. equi are not fully understood. Previously, using a SNP-based genome-wide association study, we identified a region on equine chromosome 26 associated with culture-confirmed clinical pneumonia. To better characterize this region and understand the function of the SNP located within TRPM2 that was associated with R. equi pneumonia, we performed RNA-Seq on 12 horses repres...
Dwarfism with joint laxity in Friesian horses is associated with a splice site mutation in B4GALT7. Inbreeding and population bottlenecks in the ancestry of Friesian horses has led to health issues such as dwarfism. The limbs of dwarfs are short and the ribs are protruding inwards at the costochondral junction, while the head and back appear normal. A striking feature of the condition is the flexor tendon laxity that leads to hyperextension of the fetlock joints. The growth plates of dwarfs display disorganized and thickened chondrocyte columns. The aim of this study was to identify the gene defect that causes the recessively inherited trait in Friesian horses to understand the disease proce...
Novel equine tissue miRNAs and breed-related miRNA expressed in serum. MiRNAs regulate multiple genes at the post-transcriptional level and therefore play an important role in many biological processes. It has been suggested that miRNA exported outside the cells contribute to inter-cellular communication. Consequently, circulating miRNAs are of particular interest and are promising biomarkers for many diseases. The number of miRNAs annotated in the horse genome is much lower compared to model organisms like human and mouse. We therefore aimed to identify novel equine miRNAs for tissue types and breed in serum. We analysed 71 small RNA-seq libraries derived from n...
Differential expression of skeletal muscle genes following administration of clenbuterol to exercised horses. Clenbuterol, a beta2-adrenergic receptor agonist, is used therapeutically to treat respiratory conditions in the horse. However, by virtue of its mechanism of action it has been suggested that clenbuterol may also have repartitioning affects in horses and as such the potential to affect performance. Clenbuterol decreases the percent fat and increases fat-free mass following high dose administration in combination with intense exercise in horses. In the current study, microarray analysis and real-time PCR were used to study the temporal effects of low and high dose chronic clenbuterol administr...
Screening of whole genome sequences identified high-impact variants for stallion fertility. Stallion fertility is an economically important trait due to the increase of artificial insemination in horses. The availability of whole genome sequence data facilitates identification of rare high-impact variants contributing to stallion fertility. The aim of our study was to genotype rare high-impact variants retrieved from next-generation sequencing (NGS)-data of 11 horses in order to unravel harmful genetic variants in large samples of stallions. Methods: Gene ontology (GO) terms and search results from public databases were used to obtain a comprehensive list of human und mice genes pred...
Identification and validation of risk loci for osteochondrosis in standardbreds. Osteochondrosis (OC), simply defined as a failure of endochondral ossification, is a complex disease with both genetic and environmental risk factors that is commonly diagnosed in young horses, as well as other domestic species. Although up to 50 % of the risk for developing OC is reportedly inherited, specific genes and alleles underlying risk are thus far completely unknown. Regions of the genome identified as associated with OC vary across studies in different populations of horses. In this study, we used a cohort of Standardbred horses from the U.S. (n = 182) specifically selected for...
Deep sequencing of the uterine immune response to bacteria during the equine oestrous cycle. The steroid hormone environment in healthy horses seems to have a significant impact on the efficiency of their uterine immune response. The objective of this study was to characterize the changes in gene expression in the equine endometrium in response to the introduction of bacterial pathogens and the influence of steroid hormone concentrations on this expression. Methods: Endometrial biopsies were collected from five horses before and 3 h after the inoculation of Escherichia coli once in oestrus (follicle >35 mm in diameter) and once in dioestrus (5 days after ovulation) and analysed usi...
A nonsense mutation in B3GALNT2 is concordant with hydrocephalus in Friesian horses. Hydrocephalus in Friesian horses is a developmental disorder that often results in stillbirth of affected foals and dystocia in dams. The occurrence is probably related to a founder effect and inbreeding in the population. The aim of our study was to find genomic associations, to investigate the mode of inheritance, to allow a DNA test for hydrocephalus in Friesian horses to be developed. In case of a monogenic inheritance we aimed to identify the causal mutation. Results: A genome-wide association study of hydrocephalus in 13 cases and 69 controls using 29,720 SNPs indicated the involvement o...
Runs of homozygosity reveal signatures of positive selection for reproduction traits in breed and non-breed horses. Modern horses represent heterogeneous populations specifically selected for appearance and performance. Genomic regions under high selective pressure show characteristic runs of homozygosity (ROH) which represent a low genetic diversity. This study aims at detecting the number and functional distribution of ROHs in different horse populations using next generation sequencing data. Methods: Next generation sequencing was performed for two Sorraia, one Dülmen Horse, one Arabian, one Saxon-Thuringian Heavy Warmblood, one Thoroughbred and four Hanoverian. After quality control reads were mapped t...
Generation of a de novo transcriptome from equine lamellar tissue. Laminitis, the structural failure of interdigitated tissue that suspends the distal skeleton within the hoof capsule, is a devastating disease that is the second leading cause of both lameness and euthanasia in the horse. Current transcriptomic research focuses on the expression of known genes. However, as this tissue is quite unique and equine gene annotation is largely derived from computational predictions, there are likely yet uncharacterized transcripts that may be involved in the etiology of laminitis. In order to create a novel annotation resource, we performed whole transcriptome seque...
Whole genome sequence and analysis of the Marwari horse breed and its genetic origin. The horse (Equus ferus caballus) is one of the earliest domesticated species and has played an important role in the development of human societies over the past 5,000 years. In this study, we characterized the genome of the Marwari horse, a rare breed with unique phenotypic characteristics, including inwardly turned ear tips. It is thought to have originated from the crossbreeding of local Indian ponies with Arabian horses beginning in the 12th century. Results: We generated 101 Gb (~30 × coverage) of whole genome sequences from a Marwari horse using the Illumina HiSeq2000 sequencer. The seq...
Omics technologies provide new insights into the molecular physiopathology of equine osteochondrosis. Osteochondrosis (OC(D)) is a juvenile osteo-articular disorder affecting several mammalian species. In horses, OC(D) is considered as a multifactorial disease and has been described as a focal disruption of endochondral ossification leading to the development of osteoarticular lesions. Nevertheless, OC(D) physiopathology is poorly understood. Affected horses may present joint swelling, stiffness and lameness. Thus, OC(D) is a major concern for the equine industry. Our study was designed as an integrative approach using omics technologies for the identification of constitutive defects in epiphy...
Next-generation sequencing identifies equine cartilage and subchondral bone miRNAs and suggests their involvement in osteochondrosis physiopathology. MicroRNAs (miRNAs) are an abundant class of small single-stranded non-coding RNA molecules ranging from 18 to 24 nucleotides. They negatively regulate gene expression at the post-transcriptional level and play key roles in many biological processes, including skeletal development and cartilage maturation. In addition, miRNAs involvement in osteoarticular diseases has been proved and some of them were identified as suitable biomarkers for pathological conditions. Equine osteochondrosis (OC) is one of the most prevalent juvenile osteoarticular disorders in horses and represents a major concern f...
Genome-wide analysis of DNA methylation patterns in horse. DNA methylation is an epigenetic regulatory mechanism that plays an essential role in mediating biological processes and determining phenotypic plasticity in organisms. Although the horse reference genome and whole transcriptome data are publically available the global DNA methylation data are yet to be known. Results: We report the first genome-wide DNA methylation characteristics data from skeletal muscle, heart, lung, and cerebrum tissues of thoroughbred (TH) and Jeju (JH) horses, an indigenous Korea breed, respectively by methyl-DNA immunoprecipitation sequencing. The analysis of the DNA m...
Next generation sequencing gives an insight into the characteristics of highly selected breeds versus non-breed horses in the course of domestication. Domestication has shaped the horse and lead to a group of many different types. Some have been under strong human selection while others developed in close relationship with nature. The aim of our study was to perform next generation sequencing of breed and non-breed horses to provide an insight into genetic influences on selective forces. Results: Whole genome sequencing of five horses of four different populations revealed 10,193,421 single nucleotide polymorphisms (SNPs) and 1,361,948 insertion/deletion polymorphisms (indels). In comparison to horse variant databases and previous reports, w...
Genomic analysis establishes correlation between growth and laryngeal neuropathy in Thoroughbreds. Equine recurrent laryngeal neuropathy (RLN) is a bilateral mononeuropathy with an unknown pathogenesis that significantly affects performance in Thoroughbreds. A genetic contribution to the pathogenesis of RLN is suggested by the higher prevalence of the condition in offspring of RLN-affected than unaffected stallions. To better understand RLN pathogenesis and its genetic basis, we performed a genome-wide association (GWAS) of 282 RLN-affected and 268 control Thoroughbreds. Results: We found a significant association of RLN with the LCORL/NCAPG locus on ECA3 previously shown to affect body siz...
A genome-wide association study demonstrates significant genetic variation for fracture risk in Thoroughbred racehorses. Thoroughbred racehorses are subject to non-traumatic distal limb bone fractures that occur during racing and exercise. Susceptibility to fracture may be due to underlying disturbances in bone metabolism which have a genetic cause. Fracture risk has been shown to be heritable in several species but this study is the first genetic analysis of fracture risk in the horse. Results: Fracture cases (n = 269) were horses that sustained catastrophic distal limb fractures while racing on UK racecourses, necessitating euthanasia. Control horses (n = 253) were over 4 years of age, were racing during the s...
Analysis of copy number variants by three detection algorithms and their association with body size in horses. Copy number variants (CNVs) have been shown to play an important role in genetic diversity of mammals and in the development of many complex phenotypic traits. The aim of this study was to perform a standard comparative evaluation of CNVs in horses using three different CNV detection programs and to identify genomic regions associated with body size in horses. Results: Analysis was performed using the Illumina Equine SNP50 genotyping beadchip for 854 horses. CNVs were detected by three different algorithms, CNVPartition, PennCNV and QuantiSNP. Comparative analysis revealed 50 CNVs that affecte...
A new genomic tool, ultra-frequently cleaving TaqII/sinefungin endonuclease with a combined 2.9-bp recognition site, applied to the construction of horse DNA libraries. Genomics and metagenomics are currently leading research areas, with DNA sequences accumulating at an exponential rate. Although enormous advances in DNA sequencing technologies are taking place, progress is frequently limited by factors such as genomic contig assembly and generation of representative libraries. A number of DNA fragmentation methods, such as hydrodynamic sharing, sonication or DNase I fragmentation, have various drawbacks, including DNA damage, poor fragmentation control, irreproducibility and non-overlapping DNA segment representation. Improvements in these limited DNA scissi...
Multiple secretoglobin 1A1 genes are differentially expressed in horses. Secretoglobin 1A1 (SCGB 1A1), also called Clara cell secretory protein, is the most abundantly secreted protein of the airway. The SCGB1A1 gene has been characterized in mammals as a single copy in the genome. However, analysis of the equine genome suggested that horses might have multiple SCGB1A1 gene copies. Non-ciliated lung epithelial cells produce SCGB 1A1 during inhalation of noxious substances to counter airway inflammation. Airway fluid and lung tissue of horses with recurrent airway obstruction (RAO), a chronic inflammatory lung disease affecting mature horses similar to environmental...