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  • 1
    Online Resource
    Online Resource
    American Association for the Advancement of Science (AAAS) ; 2020
    In:  Science Advances Vol. 6, No. 21 ( 2020-05-22)
    In: Science Advances, American Association for the Advancement of Science (AAAS), Vol. 6, No. 21 ( 2020-05-22)
    Abstract: Goat domestication was critical for agriculture and civilization, but its underlying genetic changes and selection regimes remain unclear. Here, we analyze the genomes of worldwide domestic goats, wild caprid species, and historical remains, providing evidence of an ancient introgression event from a West Caucasian tur-like species to the ancestor of domestic goats. One introgressed locus with a strong signature of selection harbors the MUC6 gene, which encodes a gastrointestinally secreted mucin. Experiments revealed that the nearly fixed introgressed haplotype confers enhanced immune resistance to gastrointestinal pathogens. Another locus with a strong signal of selection may be related to behavior. The selected alleles at these two loci emerged in domestic goats at least 7200 and 8100 years ago, respectively, and increased to high frequencies concurrent with the expansion of the ubiquitous modern mitochondrial haplogroup A. Tracking these archaeologically cryptic evolutionary transformations provides new insights into the mechanisms of animal domestication.
    Type of Medium: Online Resource
    ISSN: 2375-2548
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2020
    detail.hit.zdb_id: 2810933-8
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  • 2
    In: Journal of Clinical Investigation, American Society for Clinical Investigation, Vol. 131, No. 17 ( 2021-9-1)
    Type of Medium: Online Resource
    ISSN: 1558-8238
    Language: English
    Publisher: American Society for Clinical Investigation
    Publication Date: 2021
    detail.hit.zdb_id: 2018375-6
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  • 3
    In: Molecular Biology and Evolution, Oxford University Press (OUP), Vol. 39, No. 12 ( 2022-12-05)
    Abstract: Understanding the genetic mechanism of how animals adapt to extreme conditions is fundamental to determine the relationship between molecular evolution and changing environments. Goat is one of the first domesticated species and has evolved rapidly to adapt to diverse environments, including harsh high-altitude conditions with low temperature and poor oxygen supply but strong ultraviolet radiation. Here, we analyzed 331 genomes of domestic goats and wild caprid species living at varying altitudes (high & gt; 3000 m above sea level and low & lt; 1200 m), along with a reference-guided chromosome-scale assembly (contig-N50: 90.4 Mb) of a female Tibetan goat genome based on PacBio HiFi long reads, to dissect the genetic determinants underlying their adaptation to harsh conditions on the Qinghai-Tibetan Plateau (QTP). Population genomic analyses combined with genome-wide association studies (GWAS) revealed a genomic region harboring the 3′-phosphoadenosine 5′-phosphosulfate synthase 2 (PAPSS2) gene showing strong association with high-altitude adaptability (PGWAS = 3.62 × 10−25) in Tibetan goats. Transcriptomic data from 13 tissues revealed that PAPSS2 was implicated in hypoxia-related pathways in Tibetan goats. We further verified potential functional role of PAPSS2 in response to hypoxia in PAPSS2-deficient cells. Introgression analyses suggested that the PAPSS2 haplotype conferring the high-altitude adaptability in Tibetan goats originated from a recent hybridization between goats and a wild caprid species, the markhor (Capra falconeri). In conclusion, our results uncover a hitherto unknown contribution of PAPSS2 to high-altitude adaptability in Tibetan goats on QTP, following interspecific introgression and natural selection.
    Type of Medium: Online Resource
    ISSN: 0737-4038 , 1537-1719
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2024221-9
    SSG: 12
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  • 4
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 5, No. 1 ( 2015-09-10)
    Abstract: Recent advances in the study of the CRISPR/Cas9 system have provided a precise and versatile approach for genome editing in various species. However, the applicability and efficiency of this method in large animal models, such as the goat, have not been extensively studied. Here, by co-injection of one-cell stage embryos with Cas9 mRNA and sgRNAs targeting two functional genes ( MSTN and FGF5 ), we successfully produced gene-modified goats with either one or both genes disrupted. The targeting efficiency of MSTN and FGF5 in cultured primary fibroblasts was as high as 60%, while the efficiency of disrupting MSTN and FGF5 in 98 tested animals was 15% and 21% respectively and 10% for double gene modifications. The on- and off-target mutations of the target genes in fibroblasts, as well as in somatic tissues and testis of founder and dead animals, were carefully analyzed. The results showed that simultaneous editing of several sites was achieved in large animals, demonstrating that the CRISPR/Cas9 system has the potential to become a robust and efficient gene engineering tool in farm animals and therefore will be critically important and applicable for breeding.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2015
    detail.hit.zdb_id: 2615211-3
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  • 5
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2022
    In:  BMC Microbiology Vol. 22, No. 1 ( 2022-11-11)
    In: BMC Microbiology, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2022-11-11)
    Abstract: Myostatin ( MSTN ) negatively regulates the muscle growth in animals and MSTN deficient sheep have been widely reported previously. The goal of this study was to explore how MSTN inactivation influences their gut microbiota composition and potential functions. Results We compared the slaughter parameters and meat quality of 3 MSTN -edited male sheep and 3 wild-type male sheep, and analyzed the gut microbiome of the MSTN -edited sheep (8 female and 8 male sheep) and wild-type sheep (8 female and 8 male sheep) through metagenomic sequencing. The results showed that the body weight, carcass weight and eye muscle area of MSTN -edited sheep were significantly higher, but there were no significant differences in the meat quality indexes. At the microbial level, the alpha diversity was significantly higher in the MSTN -edited sheep ( P   〈  0.05), and the microbial composition was significantly different by PCoA analysis in the MSTN -edited and wild-type sheep. The abundance of Firmicutes significantly increased and Bacteroidota significantly decreased in the MSTN -edited sheep. At genus level, the abundance of Flavonifractor, Subdoligranulum, Ruthenibacterium, Agathobaculum, Anaerotignum, Oribacterium and Lactobacillus were significantly increased in the MSTN -edited sheep ( P   〈  0.05). Further analysis of functional differences was found that the carotenoid biosynthesis was significantly increased and the peroxisome, apoptosis, ferroptosis, N-glycan biosynthesis, thermogenesis, and adipocytokines pathways were decreased in the MSTN -edited sheep ( P   〈  0.05). Moreover, carbohydrate-active enzymes (CAZymes) results certified the abundance of the GH13_39, GH4, GH137, GH71 and PL17 were upregulated, and the GT41 and CBM20 were downregulated in the MSTN -edited sheep ( P   〈  0.05). Conclusions Our study suggested that MSTN inactivation remarkably influenced the composition and potential function of hindgut microbial communities of the sheep, and significantly promoted growth performance without affecting meat quality.
    Type of Medium: Online Resource
    ISSN: 1471-2180
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2041505-9
    SSG: 12
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  • 6
    In: Reproduction, Fertility and Development, CSIRO Publishing, Vol. 31, No. 9 ( 2019), p. 1533-
    Abstract: The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system is an efficient method for the production of gene-edited animals. We have successfully generated gene-modified goats and sheep via zygote injection of Cas9 mRNA and single-guide RNA (sgRNA) mixtures. However, the delivery system for microinjection largely refers to methods established for mice; optimised injection conditions are urgently required for the generation of large animals. Here, we designed a study to optimise the Cas9 mRNA and sgRNA delivery system for goats. By comparing four computational tools for sgRNA design and validating the targeting efficiency in goat fibroblasts, we suggest a protocol for the selection of desirable sgRNAs with higher targeting efficiency and negligible off-target mutations. We further evaluated the editing efficiency in goat zygotes injected with Cas9:sgRNA (sg8) and found that injection with 50ngμL−1 Cas9 mRNA and 25ngμL−1 sgRNA yielded an increased editing efficiency. Our results provide a reference protocol for the optimisation of the injection conditions for the efficient editing of large animal genomes via the zygote injection approach.
    Type of Medium: Online Resource
    ISSN: 1031-3613
    Language: English
    Publisher: CSIRO Publishing
    Publication Date: 2019
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2018
    In:  BMC Genomics Vol. 19, No. 1 ( 2018-12)
    In: BMC Genomics, Springer Science and Business Media LLC, Vol. 19, No. 1 ( 2018-12)
    Type of Medium: Online Resource
    ISSN: 1471-2164
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2018
    detail.hit.zdb_id: 2041499-7
    SSG: 12
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  • 8
    In: BMC Genomics, Springer Science and Business Media LLC, Vol. 24, No. 1 ( 2023-06-12)
    Abstract: Rewriting the genomes of living organisms has been a long-standing aim in the biological sciences. The revelation of the CRISPR/Cas9 technology has revolutionized the entire biological field. Since its emergence, this technology has been widely applied to induce gene knockouts, insertions, deletions, and base substitutions. However, the classical version of this system was imperfect for inducing or correcting desired mutations. A subsequent development generated more advanced classes, including cytosine and adenine base editors, which can be used to achieve single nucleotide substitutions. Nevertheless, these advanced systems still suffer from several limitations, such as the inability to edit loci without a suitable PAM sequence and to induce base transversions. On the other hand, the recently emerged prime editors (PEs) can achieve all possible single nucleotide substitutions as well as targeted insertions and deletions, which show promising potential to alter and correct the genomes of various organisms. Of note, the application of PE to edit livestock genomes has not been reported yet. Results In this study, using PE, we successfully generated sheep with two agriculturally significant mutations, including the fecundity-related FecB B p.Q249R and the tail length-related TBXT p.G112W. Additionally, we applied PE to generate porcine blastocysts with a biomedically relevant point mutation ( KCNJ5 p.G151R) as a porcine model of human primary aldosteronism. Conclusions Our study demonstrates the potential of the PE system to edit the genomes of large animals for the induction of economically desired mutations and for modeling human diseases. Although prime-edited sheep and porcine blastocysts could be generated, the editing frequencies are still unsatisfactory, highlighting the need for optimizations in the PE system for efficient generation of large animals with customized traits.
    Type of Medium: Online Resource
    ISSN: 1471-2164
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2041499-7
    SSG: 12
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  • 9
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2013
    In:  BMC Genomics Vol. 14, No. 1 ( 2013-12)
    In: BMC Genomics, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2013-12)
    Abstract: MicroRNAs (miRNAs) are a large family of endogenous, non-coding RNAs, about 22 nucleotides long, which regulate gene expression through sequence-specific base pairing with target mRNAs. Extensive studies have shown that miRNA expression in the skin changes remarkably during distinct stages of the hair cycle in humans, mice, goats and sheep. Results In this study, the skin tissues were harvested from the three stages of hair follicle cycling (anagen, catagen and telogen) in a fibre-producing goat breed. In total, 63,109,004 raw reads were obtained by Solexa sequencing and 61,125,752 clean reads remained for the small RNA digitalisation analysis. This resulted in the identification of 399 conserved miRNAs; among these, 326 miRNAs were expressed in all three follicular cycling stages, whereas 3, 12 and 11 miRNAs were specifically expressed in anagen, catagen, and telogen, respectively. We also identified 172 potential novel miRNAs by Mireap, 36 miRNAs were expressed in all three cycling stages, whereas 23, 29 and 44 miRNAs were specifically expressed in anagen, catagen, and telogen, respectively. The expression level of five arbitrarily selected miRNAs was analyzed by quantitative PCR, and the results indicated that the expression patterns were consistent with the Solexa sequencing results. Gene Ontology and KEGG pathway analyses indicated that five major biological pathways (Metabolic pathways, Pathways in cancer, MAPK signalling pathway, Endocytosis and Focal adhesion) accounted for 23.08% of target genes among 278 biological functions, indicating that these pathways are likely to play significant roles during hair cycling. Conclusions During all hair cycle stages of cashmere goats, a large number of conserved and novel miRNAs were identified through a high-throughput sequencing approach. This study enriches the Capra hircus miRNA databases and provides a comprehensive miRNA transcriptome profile in the skin of goats during the hair follicle cycle.
    Type of Medium: Online Resource
    ISSN: 1471-2164
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2013
    detail.hit.zdb_id: 2041499-7
    SSG: 12
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  • 10
    In: Reproduction, Fertility and Development, CSIRO Publishing, Vol. 30, No. 12 ( 2018), p. 1616-
    Abstract: Since its emergence, the clustered regularly interspaced short palindromic repeat (CRISPR)–CRISPR-associated (Cas) 9 system has been increasingly used to generate animals for economically important traits. However, most CRISPR/Cas9 applications have been focused on non-homologous end joining, which results in base deletions and insertions, leading to a functional knockout of the targeted gene. The Booroola fecundity gene (FecBB) mutation (p.Q249R) in bone morphogenetic protein receptor type 1B (BMPR1B) has been demonstrated to exert a profound effect on fecundity in many breeds of sheep. In the present study, we successfully obtained lambs with defined point mutations resulting in a p.249Q  〉  R substitution through the coinjection of Cas9 mRNA, a single guide RNA and single-stranded DNA oligonucleotides into Tan sheep zygotes. In the newborn lambs, the observed efficiency of the single nucleotide exchange was as high as 23.8%. We believe that our findings will contribute to improved reproduction traits in sheep, as well as to the generation of defined point mutations in other large animals.
    Type of Medium: Online Resource
    ISSN: 1031-3613
    Language: English
    Publisher: CSIRO Publishing
    Publication Date: 2018
    SSG: 12
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