João B. Silva Neto, Lucio F. M. Mota, Marisol Londoño-Gil, Patrícia I. Schmidt, Gustavo R. D. Rodrigues, Viviane A. Ligori, Leonardo M. Arikawa, Claudio U. Magnabosco, Luiz F. Brito, Fernando Baldi
Modern livestock production systems are characterized by a greater focus on intensification, involving managing larger numbers of animals to achieve higher productive efficiency and animal health and welfare within herds. Therefore, animal breeding programs need to be strategically designed to select animals that can effectively enhance production performance and animal welfare across a range of environmental conditions. Thus, this review summarizes the main methodologies used for assessing the levels of genotype-by-environment interaction (G × E) in cattle populations. In addition, we explored the importance of integrating genomic and phenotypic information to quantify and account for G × E in breeding programs. An overview of the structure of cattle breeding programs is provided to give insights into the potential outcomes and challenges faced when considering G × E to optimize genetic gains in breeding programs. The role of nutrigenomics and its impact on gene expression related to metabolism in cattle are also discussed, along with an examination of current research findings and their potential implications for future research and practical applications. Out of the 116 studies examined, 60 and 56 focused on beef and dairy cattle, respectively. A total of 83.62% of these studies reported genetic correlations across environmental gradients below 0.80, indicating the presence of G × E. For beef cattle, 69.33%, 24%, 2.67%, 2.67%, and 1.33% of the studies evaluated growth, reproduction, carcass and meat quality, survival, and feed efficiency traits, respectively. By contrast, G × E research in dairy cattle populations predominantly focused on milk yield and milk composition (79.36% of the studies), followed by reproduction and fertility (19.05%), and survival (1.59%) traits. The importance of G × E becomes particularly evident when considering complex traits such as heat tolerance, disease resistance, reproductive performance, and feed efficiency, as highlighted in this review. Genomic models provide a valuable avenue for studying these traits in greater depth, allowing for the identification of candidate genes and metabolic pathways associated with animal fitness, adaptation, and environmental efficiency. Nutrigenetics and nutrigenomics are emerging fields that require extensive investigation to maximize our understanding of gene–nutrient interactions. By studying various transcription factors, we can potentially improve animal metabolism, improving performance, health, and quality of products such as meat and milk.
现代畜牧生产系统的特点是更加注重集约化,包括管理更多数量的动物,以实现更高的生产效率以及畜群内的动物健康和福利。因此,需要对动物育种计划进行战略性设计,以选择能在各种环境条件下有效提高生产性能和动物福利的动物。因此,本综述总结了用于评估牛群中基因型与环境交互作用(G × E)水平的主要方法。此外,我们还探讨了在育种计划中整合基因组和表型信息以量化和考虑 G × E 的重要性。我们概述了牛育种计划的结构,以便深入了解在育种计划中考虑 G × E 以优化遗传增益时可能产生的结果和面临的挑战。此外,还讨论了营养基因组学的作用及其对牛新陈代谢相关基因表达的影响,以及当前的研究成果及其对未来研究和实际应用的潜在影响。在所研究的 116 项研究中,有 60 项和 56 项分别以肉牛和奶牛为研究对象。这些研究中共有 83.62% 报告了环境梯度遗传相关性低于 0.80,表明存在 G × E。就肉牛而言,分别有 69.33%、24%、2.67%、2.67% 和 1.33% 的研究对生长、繁殖、胴体和肉质、存活率和饲料效率性状进行了评估。相比之下,奶牛群体中的 G × E 研究主要集中在产奶量和牛奶成分(占研究的 79.36%),其次是繁殖力(19.05%)和存活率(1.59%)。在考虑耐热性、抗病性、繁殖性能和饲料效率等复杂性状时,G × E 的重要性尤为明显,这也是本综述所强调的。基因组模型为更深入地研究这些性状提供了宝贵的途径,可用于鉴定与动物体能、适应性和环境效率相关的候选基因和代谢途径。营养遗传学和营养基因组学是新兴领域,需要进行广泛的研究,以最大限度地加深我们对基因-营养素相互作用的理解。通过研究各种转录因子,我们有可能改善动物的新陈代谢,提高动物的性能、健康水平以及肉类和牛奶等产品的质量。
{"title":"Genotype-by-environment interactions in beef and dairy cattle populations: A review of methodologies and perspectives on research and applications","authors":"João B. Silva Neto, Lucio F. M. Mota, Marisol Londoño-Gil, Patrícia I. Schmidt, Gustavo R. D. Rodrigues, Viviane A. Ligori, Leonardo M. Arikawa, Claudio U. Magnabosco, Luiz F. Brito, Fernando Baldi","doi":"10.1111/age.13483","DOIUrl":"10.1111/age.13483","url":null,"abstract":"<p>Modern livestock production systems are characterized by a greater focus on intensification, involving managing larger numbers of animals to achieve higher productive efficiency and animal health and welfare within herds. Therefore, animal breeding programs need to be strategically designed to select animals that can effectively enhance production performance and animal welfare across a range of environmental conditions. Thus, this review summarizes the main methodologies used for assessing the levels of genotype-by-environment interaction (G × E) in cattle populations. In addition, we explored the importance of integrating genomic and phenotypic information to quantify and account for G × E in breeding programs. An overview of the structure of cattle breeding programs is provided to give insights into the potential outcomes and challenges faced when considering G × E to optimize genetic gains in breeding programs. The role of nutrigenomics and its impact on gene expression related to metabolism in cattle are also discussed, along with an examination of current research findings and their potential implications for future research and practical applications. Out of the 116 studies examined, 60 and 56 focused on beef and dairy cattle, respectively. A total of 83.62% of these studies reported genetic correlations across environmental gradients below 0.80, indicating the presence of G × E. For beef cattle, 69.33%, 24%, 2.67%, 2.67%, and 1.33% of the studies evaluated growth, reproduction, carcass and meat quality, survival, and feed efficiency traits, respectively. By contrast, G × E research in dairy cattle populations predominantly focused on milk yield and milk composition (79.36% of the studies), followed by reproduction and fertility (19.05%), and survival (1.59%) traits. The importance of G × E becomes particularly evident when considering complex traits such as heat tolerance, disease resistance, reproductive performance, and feed efficiency, as highlighted in this review. Genomic models provide a valuable avenue for studying these traits in greater depth, allowing for the identification of candidate genes and metabolic pathways associated with animal fitness, adaptation, and environmental efficiency. Nutrigenetics and nutrigenomics are emerging fields that require extensive investigation to maximize our understanding of gene–nutrient interactions. By studying various transcription factors, we can potentially improve animal metabolism, improving performance, health, and quality of products such as meat and milk.</p>","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/age.13483","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiuping Wang, Lei Wang, Xing Hong, Mingze Li, Xianyuan Gu, Minhui Liu, ShiJun Li
Intermittent fertilization intensity (IFI) is closely related to higher fertilization in chickens, but the genetic basis of IFI is not clearly understood. Here, we sampled a total of 939 Wenchang chickens with IFI. The IFI traits had negative correlation with the fertilization rate and exhibited huge phenotypic variations among individuals of the same strain. Based on SNPs derived from a subset of 499 whole genome data, a genome-wide association study with mixed linear model and further linkage disequilibrium analysis were performed to test potential associations between IFI traits and genomic variants. We identified 35 SNP variants and a 19.82 kb linkage disequilibrium block on chr8 significantly associated with IFI. This block is in the intron of LOC101750715, which shows significant homology with the human LMO4. Therefore, LOC101750715 and LMO4 may regulate IFI. The oviduct's immune regulation is crucial for fertilization. LMO4, activated by IL-6 and IL-23, promotes inflammation in epithelial cells. Thus, LOC101750715 and LMO4 may affect fertilization by regulating oviductal inflammation, impacting IFI. Our findings will provide targets for molecular-marker selection and genetic manipulation for lines of chickens with lower IFI.
{"title":"Genome-wide re-sequencing reveals regulatory genes and variants involved in the regulation of intermittent fertilization intensity in Wenchang chickens","authors":"Xiuping Wang, Lei Wang, Xing Hong, Mingze Li, Xianyuan Gu, Minhui Liu, ShiJun Li","doi":"10.1111/age.13471","DOIUrl":"10.1111/age.13471","url":null,"abstract":"<p>Intermittent fertilization intensity (IFI) is closely related to higher fertilization in chickens, but the genetic basis of IFI is not clearly understood. Here, we sampled a total of 939 Wenchang chickens with IFI. The IFI traits had negative correlation with the fertilization rate and exhibited huge phenotypic variations among individuals of the same strain. Based on SNPs derived from a subset of 499 whole genome data, a genome-wide association study with mixed linear model and further linkage disequilibrium analysis were performed to test potential associations between IFI traits and genomic variants. We identified 35 SNP variants and a 19.82 kb linkage disequilibrium block on chr8 significantly associated with IFI. This block is in the intron of LOC101750715, which shows significant homology with the human LMO4. Therefore, LOC101750715 and LMO4 may regulate IFI. The oviduct's immune regulation is crucial for fertilization. LMO4, activated by IL-6 and IL-23, promotes inflammation in epithelial cells. Thus, LOC101750715 and LMO4 may affect fertilization by regulating oviductal inflammation, impacting IFI. Our findings will provide targets for molecular-marker selection and genetic manipulation for lines of chickens with lower IFI.</p>","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>In the past decades, multiple genome-wide association studies have been performed to identify loci affecting milk production traits, including some using imputed whole-genome sequence data (i.e. Daetwyler et al., <span>2014</span>; Fang & Pausch, <span>2019</span>; Sanchez et al., <span>2017</span>). Several genome-wide association studies have linked a polymorphism (rs136067046, BTA19: g.50775172 C>G on ARS-UCD1.2) located in the upstream region of <i>FASN</i> (encoding fatty acid synthase) to milk fat traits in dairy cattle (Cai et al., <span>2020</span>; Sanchez et al., <span>2019</span>; Tribout et al., <span>2020</span>). For example, Cai and collaborators showed that rs136067046 is associated to milk fat traits in Nordic Holstein cows. FASN is an enzyme that plays a critical role in de novo fatty acid synthesis in milk. Interestingly, rs136067046 is located within an ATAC peak (chr.19: 50 773 523–50 795 886) found in the mammary gland (Yuan et al., <span>2023</span>). It is thus possible that rs136067046 is a functional variant that directly impacts these traits.</p><p>The ability of this SNP to alter transcription factor binding sites was then predicted with a custom script, as previously described (Ramírez-Ayala et al., <span>2021</span>). This analysis suggests that rs136067046 modifies the binding sites of nine transcription factors (Table 1). Five of those transcription factors are expressed (transcript per million reads ≥0.5) in mammary gland tissue (Fang et al., <span>2020</span>). Interestingly, three of those five transcription factors are from the Krüppel-like factor (KLF) family, a conserved class of transcription factors. It has been shown that KLF4 promotes milk fat synthesis in bovine mammary epithelial cells by targeting the <i>FASN</i> promoter region (Wu et al., <span>2024</span>). The authors have shown, using yeast one-hybrid assay, that KLF4 interacts directly with a part of the <i>FASN</i> promoter region, encompassing the location of rs136067046. It has also been shown that KLF5 controls the expression of <i>FASN</i> through an interaction with SREBBP-1 (Lee et al., <span>2009</span>). In addition, inactivation of <i>KLF6</i> in bovine mammary epithelial cells increases <i>FASN</i> expression (Iqbal et al., <span>2022</span>). These studies point to the important role played by these KLF transcription factors in the regulation of <i>FASN</i>. All these findings suggest that, consequently, rs136067046 is potentially a regulatory variant that might alter the expression of <i>FASN</i>.</p><p>To investigate the potential regulatory function of the rs136067046 variant, we constructed and then functionally tested two allele-specific recombinant promoter vectors using the dual-luciferase reporter system and the bovine mammary epithelial MAC-T cell line (Huynh et al., <span>1991</span>). Details on the plasmid constructions and luciferase assays are provided in Supplementary Material S1. The construct with the G alle
{"title":"Identification of a functional single nucleotide polymorphism in the FASN promoter associated with milk fat traits in dairy cattle","authors":"Mélissa Poncet, Maureen Féménia, Mathieu Charles, Maxime Ben Braiek, Lorraine Bourgeois-Brunel, Hiroaki Taniguchi, Nathalie Duprat, Arnaud Boulling, Véronique Blanquet, Dominique Rocha","doi":"10.1111/age.13477","DOIUrl":"10.1111/age.13477","url":null,"abstract":"<p>In the past decades, multiple genome-wide association studies have been performed to identify loci affecting milk production traits, including some using imputed whole-genome sequence data (i.e. Daetwyler et al., <span>2014</span>; Fang & Pausch, <span>2019</span>; Sanchez et al., <span>2017</span>). Several genome-wide association studies have linked a polymorphism (rs136067046, BTA19: g.50775172 C>G on ARS-UCD1.2) located in the upstream region of <i>FASN</i> (encoding fatty acid synthase) to milk fat traits in dairy cattle (Cai et al., <span>2020</span>; Sanchez et al., <span>2019</span>; Tribout et al., <span>2020</span>). For example, Cai and collaborators showed that rs136067046 is associated to milk fat traits in Nordic Holstein cows. FASN is an enzyme that plays a critical role in de novo fatty acid synthesis in milk. Interestingly, rs136067046 is located within an ATAC peak (chr.19: 50 773 523–50 795 886) found in the mammary gland (Yuan et al., <span>2023</span>). It is thus possible that rs136067046 is a functional variant that directly impacts these traits.</p><p>The ability of this SNP to alter transcription factor binding sites was then predicted with a custom script, as previously described (Ramírez-Ayala et al., <span>2021</span>). This analysis suggests that rs136067046 modifies the binding sites of nine transcription factors (Table 1). Five of those transcription factors are expressed (transcript per million reads ≥0.5) in mammary gland tissue (Fang et al., <span>2020</span>). Interestingly, three of those five transcription factors are from the Krüppel-like factor (KLF) family, a conserved class of transcription factors. It has been shown that KLF4 promotes milk fat synthesis in bovine mammary epithelial cells by targeting the <i>FASN</i> promoter region (Wu et al., <span>2024</span>). The authors have shown, using yeast one-hybrid assay, that KLF4 interacts directly with a part of the <i>FASN</i> promoter region, encompassing the location of rs136067046. It has also been shown that KLF5 controls the expression of <i>FASN</i> through an interaction with SREBBP-1 (Lee et al., <span>2009</span>). In addition, inactivation of <i>KLF6</i> in bovine mammary epithelial cells increases <i>FASN</i> expression (Iqbal et al., <span>2022</span>). These studies point to the important role played by these KLF transcription factors in the regulation of <i>FASN</i>. All these findings suggest that, consequently, rs136067046 is potentially a regulatory variant that might alter the expression of <i>FASN</i>.</p><p>To investigate the potential regulatory function of the rs136067046 variant, we constructed and then functionally tested two allele-specific recombinant promoter vectors using the dual-luciferase reporter system and the bovine mammary epithelial MAC-T cell line (Huynh et al., <span>1991</span>). Details on the plasmid constructions and luciferase assays are provided in Supplementary Material S1. The construct with the G alle","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/age.13477","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gunnar Kleinau, Bice Chini, Leif Andersson, Patrick Scheerer
The domestication of plants and animals has resulted in one of the most significant cultural and socio-economical transitions in human history. Domestication of animals, including human-supervised reproduction, largely uncoupled particular animal species from their natural, evolutionary history driven by environmental and ecological factors. The primary motivations for domesticating animals were, and still are, producing food and materials (e.g. meat, eggs, honey or milk products, wool, leather products, jewelry and medication products) to support plowing in agriculture or in transportation (e.g. horse, cattle, camel and llama) and to facilitate human activities (for hunting, rescuing, therapeutic aid, guarding behavior and protecting or just as a companion). In recent years, decoded genetic information from more than 40 domesticated animal species have become available; these studies have identified genes and mutations associated with specific physiological and behavioral traits contributing to the complex genetic background of animal domestication. These breeding-altered genomes provide insights into the regulation of different physiological areas, including information on links between e.g. endocrinology and behavior, with important pathophysiological implications (e.g. for obesity and cancer), extending the interest in domestication well beyond the field. Several genes that have undergone selection during domestication and breeding encode specific G protein-coupled receptors, a class of membrane-spanning receptors involved in the regulation of a number of overarching functions such as reproduction, development, body homeostasis, metabolism, stress responses, cognition, learning and memory. Here we summarize the available literature on variations in G protein-coupled receptors and their ligands and how these have contributed to animal domestication.
动植物驯化是人类历史上最重要的文化和社会经济转型之一。动物驯化,包括人类监督下的繁殖,在很大程度上使特定动物物种脱离了由环境和生态因素驱动的自然进化史。驯化动物的主要动机过去是,现在仍然是,生产食物和材料(如肉、蛋、蜂蜜或奶制品、羊毛、皮革制品、珠宝首饰和药物制品),以支持农业耕作或运输(如马、牛、骆驼和美洲驼),以及为人类活动提供便利(用于狩猎、救援、辅助治疗、看守行为和保护,或仅仅作为伴侣)。近年来,已有 40 多个驯化动物物种的基因信息被解码;这些研究确定了与特定生理和行为特征相关的基因和突变,从而揭示了动物驯化的复杂遗传背景。这些经过繁殖改变的基因组提供了对不同生理领域调控的见解,包括内分泌学和行为学等之间联系的信息,具有重要的病理生理学意义(如肥胖和癌症),使驯化的兴趣远远超出了这一领域。在驯化和育种过程中经过选择的一些基因编码特异性 G 蛋白偶联受体,这是一类跨膜受体,参与调节许多重要功能,如繁殖、发育、体内平衡、新陈代谢、应激反应、认知、学习和记忆。在此,我们总结了有关 G 蛋白偶联受体及其配体的变异以及这些变异如何促进动物驯化的现有文献。
{"title":"The role of G protein-coupled receptors and their ligands in animal domestication","authors":"Gunnar Kleinau, Bice Chini, Leif Andersson, Patrick Scheerer","doi":"10.1111/age.13476","DOIUrl":"10.1111/age.13476","url":null,"abstract":"<p>The domestication of plants and animals has resulted in one of the most significant cultural and socio-economical transitions in human history. Domestication of animals, including human-supervised reproduction, largely uncoupled particular animal species from their natural, evolutionary history driven by environmental and ecological factors. The primary motivations for domesticating animals were, and still are, producing food and materials (e.g. meat, eggs, honey or milk products, wool, leather products, jewelry and medication products) to support plowing in agriculture or in transportation (e.g. horse, cattle, camel and llama) and to facilitate human activities (for hunting, rescuing, therapeutic aid, guarding behavior and protecting or just as a companion). In recent years, decoded genetic information from more than 40 domesticated animal species have become available; these studies have identified genes and mutations associated with specific physiological and behavioral traits contributing to the complex genetic background of animal domestication. These breeding-altered genomes provide insights into the regulation of different physiological areas, including information on links between e.g. endocrinology and behavior, with important pathophysiological implications (e.g. for obesity and cancer), extending the interest in domestication well beyond the field. Several genes that have undergone selection during domestication and breeding encode specific G protein-coupled receptors, a class of membrane-spanning receptors involved in the regulation of a number of overarching functions such as reproduction, development, body homeostasis, metabolism, stress responses, cognition, learning and memory. Here we summarize the available literature on variations in G protein-coupled receptors and their ligands and how these have contributed to animal domestication.</p>","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/age.13476","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cleo Schwarz, Vidhya Jagannathan, Claude Schelling, Tosso Leeb
Muscular dystrophies represent a group of disorders characterized by progressive muscle degeneration and weakness. An important subgroup are the dystrophin-related muscular dystrophies caused by variants in the DMD gene. They can be divided into the more severe Duchenne muscular dystrophy and the milder Becker muscular dystrophy. Here, we characterize the clinical, histopathological and molecular genetic aspects of two male Entlebucher Mountain Dogs with clinical signs of muscular dystrophy. The two dogs presented with marked dysphagia starting at the age of several weeks and in the later course recognizable exercise intolerance with highly increased serum creatine kinase levels. Histopathological signs of a dystrophic myopathy represented by degeneration of muscle fibers and signs of regeneration were present. Whole genome sequencing of one affected dog identified an intragenic 8.6 kb duplication in the X-chromosomal DMD gene, c.7528-4048_7645 + 4450dup. No other protein-changing variants in candidate genes for muscular dystrophy were identified. The duplication includes exon 52 of DMD and is predicted to lead to a frameshift and truncation of 30% of the wild-type open reading frame. Genotyping of the whole family confirmed the presence of the mutant allele in both affected dogs and the unaffected dam. The correct co-segregation of the mutant allele in the affected family as well as knowledge from humans and other species suggest the identified DMD variant as the most likely candidate variant for the muscular dystrophy phenotype in the two investigated dogs.
{"title":"Intragenic dystrophin (DMD) duplication variant in Entlebucher Mountain Dogs with Duchenne muscular dystrophy","authors":"Cleo Schwarz, Vidhya Jagannathan, Claude Schelling, Tosso Leeb","doi":"10.1111/age.13475","DOIUrl":"10.1111/age.13475","url":null,"abstract":"<p>Muscular dystrophies represent a group of disorders characterized by progressive muscle degeneration and weakness. An important subgroup are the dystrophin-related muscular dystrophies caused by variants in the <i>DMD</i> gene. They can be divided into the more severe Duchenne muscular dystrophy and the milder Becker muscular dystrophy. Here, we characterize the clinical, histopathological and molecular genetic aspects of two male Entlebucher Mountain Dogs with clinical signs of muscular dystrophy. The two dogs presented with marked dysphagia starting at the age of several weeks and in the later course recognizable exercise intolerance with highly increased serum creatine kinase levels. Histopathological signs of a dystrophic myopathy represented by degeneration of muscle fibers and signs of regeneration were present. Whole genome sequencing of one affected dog identified an intragenic 8.6 kb duplication in the X-chromosomal <i>DMD</i> gene, c.7528-4048_7645 + 4450dup. No other protein-changing variants in candidate genes for muscular dystrophy were identified. The duplication includes exon 52 of <i>DMD</i> and is predicted to lead to a frameshift and truncation of 30% of the wild-type open reading frame. Genotyping of the whole family confirmed the presence of the mutant allele in both affected dogs and the unaffected dam. The correct co-segregation of the mutant allele in the affected family as well as knowledge from humans and other species suggest the identified <i>DMD</i> variant as the most likely candidate variant for the muscular dystrophy phenotype in the two investigated dogs.</p>","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/age.13475","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Petretto, M. G. Luigi-Sierra, G. M. Vacca, A. Martínez, J. V. Delgado, J. Fernández Álvarez, A. Castelló, M. Pazzola, J. Jordana, M. L. Dettori, M. Amills
There is evidence that Murciano Granadina (MG), the most important caprine dairy breed in Spain, has been introgressed by African goats, but the precise geographic origin of such introgression has not been identified yet. Moreover, an accurate estimate of the magnitude of this African introgression is lacking, since current estimates are based on small numbers of sampled individuals. The aim of our work was to tackle these two issues by genotyping 500 MG goats with the Goat SNP50 BeadChip and comparing their genotypes with those of reference populations from Spain (Bermeya), France (Saanen), Morocco (Barcha, Draa, Ghazalia, Noire de Atlas, Nord, Moroccan), Egypt (Barki, Oasis, Saidi), Algeria (Arabia, Makatia, M'Zabite, Kabyle), Tunisia (Tunisian native breeds) and Sudan (Desert, Nilotic, Taggar). The population of 500 MG goats was subdivided into 10 datasets of 50 individuals to ensure that sample sizes of the target (MG) and reference populations are balanced. Performance of an unsupervised ADMIXTURE analysis demonstrated that MG goats have a North African ancestry, with an average proportion of 4.4 ± 2.3%. Next, we did a supervised ADMIXTURE analysis that revealed that the Moroccan genetic component reaches a proportion of 4.01 ± 3.9% in MG goats, while the Algerian (0.001 ± 0.001%), Egyptian (0.2 ± 0.1%), Sudanese (0.1 ± 0.1%) and Tunisian (0.3 ± 0.4%) components are present in extremely small proportions. The historical circumstances of this introgression event are currently unknown, but several plausible scenarios are outlined. Moreover, our results show considerable inter-individual heterogeneity regarding the magnitude of the Moroccan introgression of MG goats (0%– 12% depending on the MG data set under analysis). This result implies that reliable estimates about the introgression of autochthonous livestock by exotic breeds can only be obtained by extensively sampling target populations.
{"title":"The African introgression of Murciano Granadina goats has a Moroccan origin and displays remarkable levels of inter-individual variability","authors":"E. Petretto, M. G. Luigi-Sierra, G. M. Vacca, A. Martínez, J. V. Delgado, J. Fernández Álvarez, A. Castelló, M. Pazzola, J. Jordana, M. L. Dettori, M. Amills","doi":"10.1111/age.13472","DOIUrl":"10.1111/age.13472","url":null,"abstract":"<p>There is evidence that Murciano Granadina (MG), the most important caprine dairy breed in Spain, has been introgressed by African goats, but the precise geographic origin of such introgression has not been identified yet. Moreover, an accurate estimate of the magnitude of this African introgression is lacking, since current estimates are based on small numbers of sampled individuals. The aim of our work was to tackle these two issues by genotyping 500 MG goats with the Goat SNP50 BeadChip and comparing their genotypes with those of reference populations from Spain (<i>Bermeya</i>), France (<i>Saanen</i>), Morocco (<i>Barcha</i>, <i>Draa</i>, <i>Ghazalia</i>, <i>Noire de Atlas</i>, <i>Nord</i>, <i>Moroccan</i>), Egypt (<i>Barki</i>, <i>Oasis</i>, <i>Saidi</i>), Algeria (<i>Arabia</i>, <i>Makatia</i>, <i>M'Zabite, Kabyle</i>), Tunisia (<i>Tunisian native breeds</i>) and Sudan (<i>Desert</i>, <i>Nilotic</i>, <i>Taggar</i>). The population of 500 MG goats was subdivided into 10 datasets of 50 individuals to ensure that sample sizes of the target (MG) and reference populations are balanced. Performance of an unsupervised ADMIXTURE analysis demonstrated that MG goats have a North African ancestry, with an average proportion of 4.4 ± 2.3%. Next, we did a supervised ADMIXTURE analysis that revealed that the Moroccan genetic component reaches a proportion of 4.01 ± 3.9% in MG goats, while the Algerian (0.001 ± 0.001%), Egyptian (0.2 ± 0.1%), Sudanese (0.1 ± 0.1%) and Tunisian (0.3 ± 0.4%) components are present in extremely small proportions. The historical circumstances of this introgression event are currently unknown, but several plausible scenarios are outlined. Moreover, our results show considerable inter-individual heterogeneity regarding the magnitude of the Moroccan introgression of MG goats (0%– 12% depending on the MG data set under analysis). This result implies that reliable estimates about the introgression of autochthonous livestock by exotic breeds can only be obtained by extensively sampling target populations.</p>","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/age.13472","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yinjiao Zhang, Yunchang Zheng, Wenli Yu, Lidan Yang, Cui Zhang, Shujing Li, Shijie Li
In mammals, imprinted genes are characterised by a monoallelic expression, which is based on parental origin and is essential for both foetal and placental development. The ZFAT gene encodes a transcriptional factor, and its non-coding antisense RNA, ZFAT-AS1, overlaps with the ZFAT locus. Both ZFAT and ZFAT-AS1 are maternally imprinted in human placentas. In bovines, the imprinting status of the ZFAT and ZFAT-AS1 genes has yet to be reported. In this study, we analysed the allelic expression of three transcript variants (X1–X3) of the bovine ZFAT and ZFAT-AS1 genes in somatic tissues and placentas using a single nucleotide polymorphism-based method. The results showed that bovine ZFAT exhibited isoform-specific paternal expression. The ZFAT X2 variant exhibited monoallelic expression in the bovine placentas and biallelic expression in the six bovine somatic tissues (heart, liver, spleen, lung, kidney and brain). However, the ZFAT X1 and X3 variants were biallelically expressed in both bovine tissues and placentas. A 311 bp bovine ZFAT-AS1 complementary DNA (cDNA) sequence was obtained by aligning the human ZFAT-AS1 cDNA sequence with the bovine genome and conducting reverse transcription polymerase chain reaction amplification. Bovine ZFAT-AS1 have monoallelic expression in bovine placentas and somatic tissues. In addition, the DNA methylation of two regions was characterised, including the partial promoter, and exon 1 and intron 1 regions of ZFAT, and there were no differentially methylated regions.
{"title":"ZFAT (isoform-specific) and its antisense RNA 1 (ZFAT-AS1) are two allele-specific monoallelically expressed genes in cattle","authors":"Yinjiao Zhang, Yunchang Zheng, Wenli Yu, Lidan Yang, Cui Zhang, Shujing Li, Shijie Li","doi":"10.1111/age.13473","DOIUrl":"10.1111/age.13473","url":null,"abstract":"<p>In mammals, imprinted genes are characterised by a monoallelic expression, which is based on parental origin and is essential for both foetal and placental development. The <i>ZFAT</i> gene encodes a transcriptional factor, and its non-coding antisense RNA, <i>ZFAT-AS1</i>, overlaps with the <i>ZFAT</i> locus. Both <i>ZFAT</i> and <i>ZFAT-AS1</i> are maternally imprinted in human placentas. In bovines, the imprinting status of the <i>ZFAT</i> and <i>ZFAT-AS1</i> genes has yet to be reported. In this study, we analysed the allelic expression of three transcript variants (X1–X3) of the bovine <i>ZFAT</i> and <i>ZFAT-AS1</i> genes in somatic tissues and placentas using a single nucleotide polymorphism-based method. The results showed that bovine <i>ZFAT</i> exhibited isoform-specific paternal expression. The <i>ZFAT</i> X2 variant exhibited monoallelic expression in the bovine placentas and biallelic expression in the six bovine somatic tissues (heart, liver, spleen, lung, kidney and brain). However, the <i>ZFAT</i> X1 and X3 variants were biallelically expressed in both bovine tissues and placentas. A 311 bp bovine <i>ZFAT-AS1</i> complementary DNA (cDNA) sequence was obtained by aligning the human <i>ZFAT-AS1</i> cDNA sequence with the bovine genome and conducting reverse transcription polymerase chain reaction amplification. Bovine <i>ZFAT-AS1</i> have monoallelic expression in bovine placentas and somatic tissues. In addition, the DNA methylation of two regions was characterised, including the partial promoter, and exon 1 and intron 1 regions of <i>ZFAT</i>, and there were no differentially methylated regions.</p>","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniele Colombi, Francesco Perini, Stefano Bettini, Salvatore Mastrangelo, Fabio Abeni, Giuseppe Conte, Donata Marletta, Martino Cassandro, Umberto Bernabucci, Roberta Ciampolini, Emiliano Lasagna
Climate change is a major concern for the near future and for livestock breeding. Cattle breeding, due to its greenhouse gas emissions, is one of the most implicated industries. Consequently, the main future goals are to breed animals resilient to climate change, with the aim of lowering the livestock impact on the environment and selecting animals that will be able to resist different, unsuitable, and changing climates. The aim of this literature review is to compare the most recent studies on the response and adaptation of beef cattle breeds to extreme environments, in terms of genes and pathways involved. Beef breeding is just starting to implement genomics in its selection plans, and shedding light on the genomic responses to extreme climates could speed up and simplify the adaptation of these breeds to climate change. This review discusses the genes involved in climatic stress responses, including those related to extremely cold climates, in beef and dual-purpose cattle breeds. Genes were associated with productive traits, coat and skin structure and development, thermotolerance, cellular physiology and DNA repair mechanisms, immune system, and fertility traits. The knowledge of genes and pathways involved in climate resilience should be taken into consideration for further selection in beef cattle breeding and could promote the valorization of local breeds adapted to extreme environmental conditions. The use of local or resilient breeds could enhance the environmental and social sustainability, animal welfare, and production, compared with the introduction of cosmopolitan breeds with uncertain adaptation in uncontrolled environmental areas.
气候变化是近期和畜牧业面临的主要问题。养牛业因其温室气体排放而成为受影响最大的行业之一。因此,未来的主要目标是培育适应气候变化的动物,以降低牲畜对环境的影响,并选择能够抵御不同、不适宜和不断变化的气候的动物。本文献综述旨在从相关基因和途径的角度,比较有关肉牛品种对极端环境的反应和适应性的最新研究。肉牛育种刚刚开始在其选育计划中实施基因组学,阐明基因组对极端气候的反应可加快和简化这些品种对气候变化的适应。本综述讨论了肉牛和两用牛品种中涉及气候胁迫反应的基因,包括与极寒气候相关的基因。这些基因与生产性状、皮毛结构和发育、耐热性、细胞生理和 DNA 修复机制、免疫系统和繁殖力性状有关。在肉牛育种的进一步选择中,应考虑到与气候适应性有关的基因和途径的知识,并可促进适应极端环境条件的地方品种的价值评估。与在不受控制的环境地区引进适应性不确定的世界性品种相比,使用地方品种或适应性强的品种可以提高环境和社会的可持续性、动物福利和生产。
{"title":"Genomic responses to climatic challenges in beef cattle: A review","authors":"Daniele Colombi, Francesco Perini, Stefano Bettini, Salvatore Mastrangelo, Fabio Abeni, Giuseppe Conte, Donata Marletta, Martino Cassandro, Umberto Bernabucci, Roberta Ciampolini, Emiliano Lasagna","doi":"10.1111/age.13474","DOIUrl":"10.1111/age.13474","url":null,"abstract":"<p>Climate change is a major concern for the near future and for livestock breeding. Cattle breeding, due to its greenhouse gas emissions, is one of the most implicated industries. Consequently, the main future goals are to breed animals resilient to climate change, with the aim of lowering the livestock impact on the environment and selecting animals that will be able to resist different, unsuitable, and changing climates. The aim of this literature review is to compare the most recent studies on the response and adaptation of beef cattle breeds to extreme environments, in terms of genes and pathways involved. Beef breeding is just starting to implement genomics in its selection plans, and shedding light on the genomic responses to extreme climates could speed up and simplify the adaptation of these breeds to climate change. This review discusses the genes involved in climatic stress responses, including those related to extremely cold climates, in beef and dual-purpose cattle breeds. Genes were associated with productive traits, coat and skin structure and development, thermotolerance, cellular physiology and DNA repair mechanisms, immune system, and fertility traits. The knowledge of genes and pathways involved in climate resilience should be taken into consideration for further selection in beef cattle breeding and could promote the valorization of local breeds adapted to extreme environmental conditions. The use of local or resilient breeds could enhance the environmental and social sustainability, animal welfare, and production, compared with the introduction of cosmopolitan breeds with uncertain adaptation in uncontrolled environmental areas.</p>","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/age.13474","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fatty liver disease is a common metabolic disease in chickens. This disease can lead to a decrease in egg production and increase the risk of death in chickens. Long non-coding RNAs (lncRNAs) are involved in fatty liver formation by directly targeting genes or regulating gene expression by competitively binding microRNAs. However, a large proportion of competing endogenous RNA (ceRNA) networks in fatty liver diseases are still unclear. The total of 300 Jingxing-Huang chickens were used for fatty liver model construction. Then, differentially expressed (DE) genes (DEGs) identified through whole-transcriptome sequencing from four chickens with fatty liver and four chickens without fatty liver were chosen from the F1 generation. A total of 953 DEGs were identified between the fatty liver group and the control group, including 26 DE micro (mi)RNAs and 56 DE lncRNAs. Differential expression heatmaps and volcano plots were obtained after clustering expression analysis. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that these DEGs were involved in many biological processes and signaling pathways related to fatty acid metabolism and lipid synthesis. Furthermore, cytoscape was used to construct a ceRNA network of the DE miRNAs, DE mRNAs, and DE lncRNAs. Eleven DE lncRNAs, seven DE miRNAs, and 13 DE mRNAs were found to be associated with the pathogenesis of fatty liver disease. An lncRNA–miRNA–mRNA ceRNA network was constructed to elucidate the mechanisms of fatty liver diseases, and the ENSGALT00000079786-miR-140/miR-143/miR-1a/miR-22/miR-375 network was identified. These results provide a valuable resource for further elucidating the posttranscriptional regulatory mechanisms of chicken liver and adipose fat development or deposition.
脂肪肝是鸡常见的代谢性疾病。这种疾病会导致产蛋量下降,并增加鸡的死亡风险。长非编码 RNA(lncRNA)通过直接靶向基因或竞争性结合 microRNA 来调节基因表达,从而参与脂肪肝的形成。然而,脂肪肝疾病中很大一部分竞争性内源性RNA(ceRNA)网络仍不清楚。本研究以 300 只景兴黄鸡为研究对象,构建了脂肪肝模型。然后,从F1代中选择4只脂肪肝鸡和4只非脂肪肝鸡,通过全转录组测序鉴定出差异表达(DE)基因(DEGs)。在脂肪肝组和对照组之间共鉴定出 953 个 DEGs,其中包括 26 个 DE micro (mi) RNAs 和 56 个 DE lncRNAs。聚类表达分析后得到了差异表达热图和火山图。基因本体和京都基因组百科全书富集分析表明,这些DEGs参与了与脂肪酸代谢和脂质合成相关的许多生物过程和信号通路。此外,研究人员还利用细胞镜构建了一个由 DE miRNA、DE mRNA 和 DE lncRNA 组成的 ceRNA 网络。结果发现,11个DE lncRNA、7个DE miRNA和13个DE mRNA与脂肪肝的发病机制有关。通过构建lncRNA-miRNA-mRNA ceRNA网络,阐明了脂肪肝的发病机制,并确定了ENSGALT00000079786-miR-140/miR-143/miR-1a/miR-22/miR-375网络。这些结果为进一步阐明鸡肝和脂肪发育或沉积的转录后调控机制提供了宝贵的资源。
{"title":"Core competing endogenous RNA network based on mRNA and non-coding RNA expression profiles in chicken fatty liver","authors":"Qingxing Xiao, Yonghong Zhang, Hongyu Ni, Yijing Yin, Anchong Gao, Benhai Cui, Wei Zhang, Yumei Li, Yuwei Yang","doi":"10.1111/age.13469","DOIUrl":"10.1111/age.13469","url":null,"abstract":"<p>Fatty liver disease is a common metabolic disease in chickens. This disease can lead to a decrease in egg production and increase the risk of death in chickens. Long non-coding RNAs (lncRNAs) are involved in fatty liver formation by directly targeting genes or regulating gene expression by competitively binding microRNAs. However, a large proportion of competing endogenous RNA (ceRNA) networks in fatty liver diseases are still unclear. The total of 300 Jingxing-Huang chickens were used for fatty liver model construction. Then, differentially expressed (DE) genes (DEGs) identified through whole-transcriptome sequencing from four chickens with fatty liver and four chickens without fatty liver were chosen from the F1 generation. A total of 953 DEGs were identified between the fatty liver group and the control group, including 26 DE micro (mi)RNAs and 56 DE lncRNAs. Differential expression heatmaps and volcano plots were obtained after clustering expression analysis. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that these DEGs were involved in many biological processes and signaling pathways related to fatty acid metabolism and lipid synthesis. Furthermore, <span>cytoscape</span> was used to construct a ceRNA network of the DE miRNAs, DE mRNAs, and DE lncRNAs. Eleven DE lncRNAs, seven DE miRNAs, and 13 DE mRNAs were found to be associated with the pathogenesis of fatty liver disease. An lncRNA–miRNA–mRNA ceRNA network was constructed to elucidate the mechanisms of fatty liver diseases, and the ENSGALT00000079786-miR-140/miR-143/miR-1a/miR-22/miR-375 network was identified. These results provide a valuable resource for further elucidating the posttranscriptional regulatory mechanisms of chicken liver and adipose fat development or deposition.</p>","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mario Van Poucke, Liesbet Ledeganck, Ling T. Guo, G. Diane Shelton, Sofie F. M. Bhatti, Ine Cornelis, Luc Peelman
X-linked recessive dystrophinopathies are the most common muscular dystrophies (MDs) in humans and dogs. To date, 20 breed-specific MD-associated variants are described in the canine dystrophin gene (DMD), including one associated with dystrophin-deficient MD in the Border Collie mixed breed. Here, we report the diagnosis and follow-up of mild dystrophin-deficient MD in a 5-month-old male Border Collie, associated with a novel DMD variant. Diagnosis was based on neurological examination and laboratory evaluations including creatine kinase activity, electromyography and muscle biopsies with immunofluorescent staining. Inspection of the Sashimi plots of the RNA-seq data from the affected muscle biopsy led to the discovery of a 162-bp L1 pseudoexon in DMD intron 63, introducing a frameshift and a premature stop codon (NM_001003343.1: c.9271_9272insN[162] p.(Ala3091fs*21)). Reduced DMD mRNA levels were detected for both the non-pseudoexon (50× less) and pseudoexon (3× less) containing transcripts in the affected muscle, compared with the level of the non-pseudoexon containing transcript in a control muscle, resulting in very low dystrophin protein levels and the upregulation of utrophin. Because the variant was only found in the affected dog, not in the healthy mother and grandmother, or in 108 unrelated Border Collies from the Belgian population (46 males and 62 females), it was considered a de novo variant. Although the prognosis for dystrophinopathy is generally regarded as poor, the dog stabilised at the age of 6 months and is still clinically stable at the age of 2 years.
{"title":"Exonisation of an intronic L1 element in the dystrophin gene associated with X-linked muscular dystrophy in a Border Collie dog","authors":"Mario Van Poucke, Liesbet Ledeganck, Ling T. Guo, G. Diane Shelton, Sofie F. M. Bhatti, Ine Cornelis, Luc Peelman","doi":"10.1111/age.13470","DOIUrl":"10.1111/age.13470","url":null,"abstract":"<p>X-linked recessive dystrophinopathies are the most common muscular dystrophies (MDs) in humans and dogs. To date, 20 breed-specific MD-associated variants are described in the canine <i>dystrophin</i> gene (<i>DMD</i>), including one associated with dystrophin-deficient MD in the Border Collie mixed breed. Here, we report the diagnosis and follow-up of mild dystrophin-deficient MD in a 5-month-old male Border Collie, associated with a novel <i>DMD</i> variant. Diagnosis was based on neurological examination and laboratory evaluations including creatine kinase activity, electromyography and muscle biopsies with immunofluorescent staining. Inspection of the Sashimi plots of the RNA-seq data from the affected muscle biopsy led to the discovery of a 162-bp L1 pseudoexon in <i>DMD</i> intron 63, introducing a frameshift and a premature stop codon (NM_001003343.1: c.9271_9272insN[162] p.(Ala3091fs*21)). Reduced <i>DMD</i> mRNA levels were detected for both the non-pseudoexon (50× less) and pseudoexon (3× less) containing transcripts in the affected muscle, compared with the level of the non-pseudoexon containing transcript in a control muscle, resulting in very low dystrophin protein levels and the upregulation of utrophin. Because the variant was only found in the affected dog, not in the healthy mother and grandmother, or in 108 unrelated Border Collies from the Belgian population (46 males and 62 females), it was considered a <i>de novo</i> variant. Although the prognosis for dystrophinopathy is generally regarded as poor, the dog stabilised at the age of 6 months and is still clinically stable at the age of 2 years.</p>","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}