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  • Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33 secreted from impaired vessels in the skin compared to fractionated irradiation

    Biochemical and Biophysical Research Communications | 14 August 2015

    We have revealed in a porcine skin injury model that eosinophil recruitment was dose-dependently enhanced by a single high-dose irradiation. In this study, we investigated the underlying mechanism of eosinophil-associated skin fibrosis and the effect of high-dose-per-fraction radiation. The dorsal skin of a mini-pig was divided into two sections containing 4-cm2 fields that were irradiated with 30 Gy in a single fraction or 5 fractions and biopsied regularly over 14 weeks. Eosinophil-related Th2 cytokines such as interleukin (IL)-4, IL-5, and C?C motif chemokine-11 (CCL11/eotaxin) were evaluated by quantitative real-time PCR. RNA-sequencing using 30 Gy-irradiated mouse skin and functional assays in a co-culture system of THP-1 and irradiated-human umbilical vein endothelial cells (HUVECs) were performed to investigate the mechanism of eosinophil-mediated radiation fibrosis. Single high-dose-per-fraction irradiation caused pronounced eosinophil accumulation, increased profibrotic factors collagen and transforming growth factor-β, enhanced production of eosinophil-related cytokines including IL-4, IL-5, CCL11, IL-13, and IL-33, and reduced vessels compared with 5-fraction irradiation. IL-33 notably increased in pig and mouse skin vessels after single high-dose irradiation of 30 Gy, as well as in irradiated HUVECs following 12 Gy. Blocking IL-33 suppressed the migration ability of THP-1 cells and cytokine secretion in a co-culture system of THP-1 cells and irradiated HUVECs. Hence, high-dose-per-fraction irradiation appears to enhance eosinophil-mediated fibrotic responses, and IL-33 may be a key molecule operating in eosinophil-mediated fibrosis in high-dose-per fraction irradiated skin.

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  • Multiple Genes Related to Muscle Identified through a Joint Analysis of a Two-stage Genome-wide Association Study for Racing Performance of 1, 156 Thoroughb reds

    Asian-Australasian Journal of Animal Sciences

    Thoroughbred, a relatively recent horse breed, is best known for its use in horse racing. Although myostatin (MSTN) variants have been reported to be highly associated with horse racing performance, the trait is more likely to be polygenic in nature. The purpose of this study was to identify genetic variants strongly associated with racing performance by using estimated breeding value (EBV) for race time as a phenotype. We conducted a two-stage genome-wide association study to search for genetic variants associated with the EBV. In the first stage of genome-wide association study, a relatively large number of markers (~54, 000 single-nucleotide polymorphisms, SNPs) were evaluated in a small number of samples (240 horses). In the second stage, a relatively small number of markers identified to have large effects (170 SNPs) were evaluated in a much larger number of samples (1, 156 horses). We also validated the SNPs related to MSTN known to have large effects on racing performance and found significant associations in the stage two analysis, but not in stage one. We identified 28 significant SNPs related to 17 genes. Among these, six genes have a function related to myogenesis and five genes are involved in muscle maintenance. To our knowledge, these genes are newly reported for the genetic association with racing performance of Thoroughbreds. It complements a recent horse genome-wide association studies of racing performance that identified other SNPs and genes as the most significant variants. These results will help to expand our knowledge of the polygenic nature of racing performance in Thoroughbreds.
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  • Coordinated international action to accelerate genome-to-phenome with FAANG, the Functional Annotation of Animal Genomes project

    Genome Biology

    We describe the organization of a nascent international effort, the Functional Annotation of Animal Genomes (FAANG) project, whose aim is to produce comprehensive maps of functional elements in the genomes of domesticated animal species.

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  • Time-calibrated phylogenomics of the classical swine fever viruses: genome-wide Bayesian

    PLoS ONE

    The phylogeny of classical swine fever virus (CSFV), the causative agent of classical swine fever (CSF), has been investigated extensively. However, no evolutionary research has been performed using the whole CSFV genome. In this study, we used 37 published genome sequences to investigate the time-calibrated phylogenomics of CSFV. In phylogenomic trees based on Bayesian inference (BI) and Maximum likelihood (ML), the 37 isolates were categorized into five genetic types (1.1, 1.2, 2.1, 2.3, and 3.4). Subgenotype 1.1 is divided into 3 groups and 1 unclassified isolate, 2.1 into 4 groups, 2.3 into 2 groups and 1 unclassified isolate, and subgenotype 1.2 and 3.4 consisted of one isolate each. We did not observe an apparent temporal or geographical relationship between isolates. Of the 14 genomic regions, NS4B showed the most powerful phylogenetic signal. Results of this evolutionary study using Bayesian coalescent approach indicate that CSFV has evolved at a rate of 13×.010-4 substitutions per site per year. The most recent common ancestor of CSFV appeared 2770.2 years ago, which was about 8000 years after pig domestication. The effective population size of CSFV underwent a slow increase until the 1950s, after which it has remained constant

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  • Exploring the Genetic Signature of Body Size in Yucatan Miniature Pig

    PLoS ONE

    Since being domesticated about 10, 000?12, 000 years ago, domestic pigs (Sus scrofa domesticus) have been selected for traits of economic importance, in particular large body size. However, Yucatan miniature pigs have been selected for small body size to withstand high temperature environment and for laboratory use. This renders the Yucatan miniature pig a valuable model for understanding the evolution of body size. We investigate the genetic signature for selection of body size in the Yucatan miniature pig. Phylogenetic distance of Yucatan miniature pig was compared to other large swine breeds (Yorkshire, Landrace, Duroc and wild boar). By estimating the XP-EHH statistic using re-sequencing data derived from 70 pigs, we were able to unravel the signatures of selection of body size. We found that both selections at the level of organism, and at the cellular level have occurred. Selection at the higher levels include feed intake, regulation of body weight and increase in mass while selection at the molecular level includes cell cycle and cell proliferation. Positively selected genes probed by XP-EHH may provide insight into the docile character and innate immunity as well as body size of Yucatan miniature pig.

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  • A genome-wide scan for signatures of directional selection in domesticated pigs

    BMC Genomics

    Background
    Animal domestication involved drastic phenotypic changes driven by strong artificial selection and also resulted in new populations of breeds, established by humans. This study aims to identify genes that show evidence of recent artificial selection during pig domestication.

    Results
    Whole-genome resequencing of 30 individual pigs from domesticated breeds, Landrace and Yorkshire, and 10 Asian wild boars at ~16-fold coverage was performed resulting in over 4.3 million SNPs for 19, 990 genes. We constructed a comprehensive genome map of directional selection by detecting selective sweeps using an F ST-based approach that detects directional selection in lineages leading to the domesticated breeds and using a haplotype-based test that detects ongoing selective sweeps within the breeds. We show that candidate genes under selection are significantly enriched for loci implicated in quantitative traits important to pig reproduction and production. The candidate gene with the strongest signals of directional selection belongs to group III of the metabolomics glutamate receptors, known to affect brain functions associated with eating behavior, suggesting that loci under strong selection include loci involved in behaviorial traits in domesticated pigs including tameness.

    Conclusions
    We show that a significant proportion of selection signatures coincide with loci that were previously inferred to affect phenotypic variation in pigs. We further identify functional enrichment related to behavior, such as signal transduction and neuronal activities, for those targets of selection during domestication in pigs."

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  • Genome-wide SNP identification and QTL mapping for black rot resistance in cabbage

    BMC Plant Biology

    Background
    Black rot is a destructive bacterial disease causing large yield and quality losses in Brassica oleracea. To detect quantitative trait loci (QTL) for black rot resistance, we performed whole-genome resequencing of two cabbage parental lines and genome-wide SNP identification using the recently published B. oleracea genome sequences as reference.

    Results
    Approximately 11.5 Gb of sequencing data was produced from each parental line. Reference genome-guided mapping and SNP calling revealed 674, 521 SNPs between the two cabbage lines, with an average of one SNP per 662.5 bp. Among 167 dCAPS markers derived from candidate SNPs, 117 (70.1%) were validated as bona fide SNPs showing polymorphism between the parental lines. We then improved the resolution of a previous genetic map by adding 103 markers including 87 SNP-based dCAPS markers. The new map composed of 368 markers and covers 1467.3 cM with an average interval of 3.88 cM between adjacent markers. We evaluated black rot resistance in the mapping population in three independent inoculation tests using F2:3 progenies and identified one major QTL and three minor QTLs.

    Conclusion
    We report successful utilization of whole-genome resequencing for large-scale SNP identification and development of molecular markers for genetic map construction. In addition, we identified novel QTLs for black rot resistance. The high-density genetic map will promote QTL analysis for other important agricultural traits and marker-assisted breeding of B. oleracea."

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  • Cetaceans evolution: insights from the genome sequences of common minke whales

    BMC Genomics | 22 Jan 2015

    Background

    Whales have captivated the human imagination for millennia. These incredible cetaceans are the only mammals that have adapted to life in the open oceans and have been a source of human food, fuel and tools around the globe. The transition from land to water has led to various aquatic specializations related to hairless skin and ability to regulate their body temperature in cold water.

    Results

    We present four common minke whale (Balaenoptera acutorostrata) genomes with depth of?×13?~?×17 coverage and perform resequencing technology without a reference sequence. Our results indicated the time to the most recent common ancestors of common minke whales to be about 2.3574 (95% HPD, 1.1521 ? 3.9212) million years ago. Further, we found that genes associated with epilation and tooth-development showed signatures of positive selection, supporting the morphological uniqueness of whales.

    Conclusions

    This whole-genome sequencing offers a chance to better understand the evolutionary journey of one of the largest mammals on earth.

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  • Genome-wide detection and characterization of positive selection in Korean Native Black Pig from Jeju Island

    BMC Genetics

    Background
    In the 1980s, Korean native black pigs from Jeju Island (Jeju black pigs) served as representative sample of Korean native black pigs, and efforts were made to help the species rebound from the brink of extinction, which occurred as a result of the introduction of Western pig breeds. Geographical separation of Jeju Island from the Korean peninsula has allowed Jeju black pigs not only to acquire unique characteristics but also to retain merits of rare Korean native black pigs.

    Results
    To further analyze the Jeju black pig genome, we performed whole-genome re-sequencing (average read depth of 14×) of 8 Jeju black pig and 6 Korean pigs (which live on the Korean peninsula) to compare and identify putative signatures of positive selection in Jeju black pig, the true and pure Korean native black pigs. The candidate genes potentially under positive selection in Jeju black pig support previous reports of high marbling score, rare occurrence of pale, soft, exudative (PSE) meat, but low growth rate and carcass weight compared to Western breeds.

    Conclusions
    Several candidate genes potentially under positive selection were involved in fatty acid transport and may have contributed to the unique characteristics of meat quality in JBP. Jeju black pigs can offer a unique opportunity to investigate the true genetic resource of once endangered Korean native black pigs. Further genome-wide analyses of Jeju black pigs on a larger population scale are required in order to define a conservation strategy and improvement of native pig resources."

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  • Uncovering genomic features and maternal origin of Korean Native Chicken by whole genome sequencing

    PLoS ONE

    The Korean Native Chicken (KNC) is an important endemic biological resource in Korea. While numerous studies have been conducted exploring this breed, none have used next-generation sequencing to identify its specific genomic features. We sequenced five strains of KNC and identified 10.9 million SNVs and 1.3 million InDels. Through the analysis, we found that the highly variable region common to all 5 strains had genes like PCHD15, CISD1, PIK3C2A, and NUCB2 that might be related to the phenotypic traits of the chicken such as auditory sense, growth rate and egg traits. In addition, we assembled unaligned reads that could not be mapped to the reference genome. By assembling the unaligned reads, we were able to present genomic sequences characteristic to the KNC. Based on this, we also identified genes related to the olfactory receptors and antigen that are common to all 5 strains. Finally, through the reconstructed mitochondrial genome sequences, we performed phylogenomic analysis and elucidated the maternal origin of the artificially restored KNC. Our results revealed that the KNC has multiple maternal origins which are in agreement with Korea's history of chicken breed imports. The results presented here provide a valuable basis for future research on genomic features of KNC and further understanding of KNC's origin.

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