Mammalian Genome最新文献_第5页

Fibroblasts as an in vitro model of circadian genetic and genomic studies. 将成纤维细胞作为昼夜节律遗传和基因组研究的体外模型。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2024-09-01 Epub Date: 2024-07-03 DOI: 10.1007/s00335-024-10050-7

Marcelo Francia, Merel Bot, Toni Boltz, Juan F De la Hoz, Marco Boks, René S Kahn, Roel A Ophoff

{"title":"Fibroblasts as an in vitro model of circadian genetic and genomic studies.","authors":"Marcelo Francia, Merel Bot, Toni Boltz, Juan F De la Hoz, Marco Boks, René S Kahn, Roel A Ophoff","doi":"10.1007/s00335-024-10050-7","DOIUrl":"10.1007/s00335-024-10050-7","url":null,"abstract":"Bipolar disorder (BD) is a heritable disorder characterized by shifts in mood that manifest in manic or depressive episodes. Clinical studies have identified abnormalities of the circadian system in BD patients as a hallmark of underlying pathophysiology. Fibroblasts are a well-established in vitro model for measuring circadian patterns. We set out to examine the underlying genetic architecture of circadian rhythm in fibroblasts, with the goal to assess its contribution to the polygenic nature of BD disease risk. We collected, from primary cell lines of 6 healthy individuals, temporal genomic features over a 48 h period from transcriptomic data (RNA-seq) and open chromatin data (ATAC-seq). The RNA-seq data showed that only a limited number of genes, primarily the known core clock genes such as ARNTL, CRY1, PER3, NR1D2 and TEF display circadian patterns of expression consistently across cell cultures. The ATAC-seq data identified that distinct transcription factor families, like those with the basic helix-loop-helix motif, were associated with regions that were increasing in accessibility over time. Whereas known glucocorticoid receptor target motifs were identified in those regions that were decreasing in accessibility. Further evaluation of these regions using stratified linkage disequilibrium score regression analysis failed to identify a significant presence of them in the known genetic architecture of BD, and other psychiatric disorders or neurobehavioral traits in which the circadian rhythm is affected. In this study, we characterize the biological pathways that are activated in this in vitro circadian model, evaluating the relevance of these processes in the context of the genetic architecture of BD and other disorders, highlighting its limitations and future applications for circadian genomic studies.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"432-444"},"PeriodicalIF":2.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11329553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

E3 ubiquitin ligase MARCH1 reduces inflammation and pyroptosis in cerebral ischemia-reperfusion injury via PCSK9 downregulation. E3泛素连接酶MARCH1通过下调PCSK9减少脑缺血再灌注损伤中的炎症和脓毒症。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2024-09-01 Epub Date: 2024-08-08 DOI: 10.1007/s00335-024-10055-2

Hongmei Guo, Wanli Li, Zhigang Yang, Xiaobin Xing

{"title":"E3 ubiquitin ligase MARCH1 reduces inflammation and pyroptosis in cerebral ischemia-reperfusion injury via PCSK9 downregulation.","authors":"Hongmei Guo, Wanli Li, Zhigang Yang, Xiaobin Xing","doi":"10.1007/s00335-024-10055-2","DOIUrl":"10.1007/s00335-024-10055-2","url":null,"abstract":"Pyroptosis has been regarded as caspase-1-mediated monocyte death that induces inflammation, showing a critical and detrimental role in the development of cerebral ischemia-reperfusion injury (IRI). MARCH1 is an E3 ubiquitin ligase that exerts potential anti-inflammatory functions. Therefore, the study probed into the significance of MARCH1 in inflammation and pyroptosis elicited by cerebral IRI. Middle cerebral artery occlusion/reperfusion (MCAO/R)-treated mice and oxygen glucose deprivation/reoxygenation (OGD/R)-treated hippocampal neurons were established to simulate cerebral IRI in vivo and in vitro. MARCH1 and PCSK9 expression was tested in MCAO/R-operated mice, and their interaction was identified by means of the cycloheximide assay and co-immunoprecipitation. The functional roles of MARCH1 and PCSK9 in cerebral IRI were subsequently determined by examining the neurological function, brain tissue changes, neuronal viability, inflammation, and pyroptosis through ectopic expression and knockdown experiments. PCSK9 expression was increased in the brain tissues of MCAO/R mice, while PCSK9 knockdown reduced brain damage and neurological deficits. Additionally, inflammation and pyroptosis were inhibited in OGD/R-exposed hippocampal neurons upon PCSK9 knockdown, accompanied by LDLR upregulation and NLRP3 inflammasome inactivation. Mechanistic experiments revealed that MARCH1 mediated ubiquitination and degradation of PCSK9, lowering PCSK9 protein expression. Furthermore, it was demonstrated that MARCH1 suppressed inflammation and pyroptosis after cerebral IRI by downregulating PCSK9 both in vivo and in vitro. Taken together, the present study demonstrate the protective effect of MARCH1 against cerebral IRI through PCSK9 downregulation, which might contribute to the discovery of new therapies for improving cerebral IRI.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"346-361"},"PeriodicalIF":2.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic diversity of North African populations in the 17q21 genomic region. 北非人口在 17q21 基因组区域的遗传多样性。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2024-09-01 Epub Date: 2024-07-04 DOI: 10.1007/s00335-024-10051-6

Mohsen Messaoudi, Andrew J Pakstis, Takwa Ezzaher, Sami Boussetta, Amel Ben Ammar Elgaaied, Kenneth K Kidd, Lotfi Cherni

{"title":"Genetic diversity of North African populations in the 17q21 genomic region.","authors":"Mohsen Messaoudi, Andrew J Pakstis, Takwa Ezzaher, Sami Boussetta, Amel Ben Ammar Elgaaied, Kenneth K Kidd, Lotfi Cherni","doi":"10.1007/s00335-024-10051-6","DOIUrl":"10.1007/s00335-024-10051-6","url":null,"abstract":"The demographic history of human populations in North Africa has been characterized by complex migration processes that have determined the current genetic structure of these populations. We examined the autosomal markers of eight sampled populations in northern Africa (Tunisia and Libya) to explore their genetic structure and to place them in a global context. We genotyped a set of 30 autosomal single-nucleotide polymorphisms (SNPs) extending 9.5 Mb and encompassing the 17q21 inversion region. Our data include 403 individuals from Tunisia and Libya. To put our populations in the global context, we analyzed our data in comparison with other populations, including those of the 1000 Genomes Project. To evaluate the data, we conducted genetic diversity, principal component, STRUCTURE, and haplotype analyses. The analysis of genetic composition revealed the genetic heterogeneity of North African populations. The principal component and STRUCTURE analyses converged and revealed the intermediate position of North Africans between Europeans and Asians. Haplotypic analysis demonstrated that the normal (H1) and inverted (H2) polymorphisms in the chromosome 17q21 region occur in North Africa at frequencies similar to those found in European and Southwest Asian populations. The results highlight the complex demographic history of North Africa, reflecting the influence of genetic flow from Europe and the Near East that dates to the prehistoric period. These gene flows added to demographic factors (inbreeding, endogamy), natural factors (topography, Sahara), and cultural factors that play a role in the emergence of the diverse and heterogeneous genetic structures of North African populations. This study contributes to a better understanding of the complex structure of North African populations.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"445-460"},"PeriodicalIF":2.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluation of genotype imputation using Glimpse tools on low coverage ancient DNA. 使用 Glimpse 工具对低覆盖率古 DNA 的基因型推算进行评估。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2024-09-01 Epub Date: 2024-07-19 DOI: 10.1007/s00335-024-10053-4

Hande Çubukcu, Gülşah Merve Kılınç

{"title":"Evaluation of genotype imputation using Glimpse tools on low coverage ancient DNA.","authors":"Hande Çubukcu, Gülşah Merve Kılınç","doi":"10.1007/s00335-024-10053-4","DOIUrl":"10.1007/s00335-024-10053-4","url":null,"abstract":"Ancient DNA provides a unique frame for directly studying human population genetics in time and space. Still, since most of the ancient genomic data is low coverage, analysis is confronted with a low number of SNPs, genotype uncertainties, and reference-bias. Here, we for the first time benchmark the two distinct versions of Glimpse tools on 120 ancient human genomes from Eurasia including those largely from previously under-evaluated regions and compare the performance of genotype imputation with de facto analysis approaches for low coverage genomic data analysis. We further investigate the impact of two distinct reference panels on imputation accuracy for low coverage genomic data. We compute accuracy statistics and perform PCA and f4-statistics to explore the behaviour of genotype imputation on low coverage data regarding (i)two versions of Glimpse, (ii)two reference panels, (iii)four post-imputation filters and coverages, as well as (iv)data type and geographical origin of the samples on the analyses. Our results reveal that even for 0.1X coverage ancient human genomes, genotype imputation using Glimpse-v2 is suitable. Additionally, using the 1000 Genomes merged with Human Genome Diversity Panel improves the accuracy of imputation for the rare variants with low MAF, which might be important not only for ancient genomics but also for modern human genomic studies based on low coverage data and for haplotype-based analysis. Most importantly, we reveal that genotype imputation of low coverage ancient human genomes reduces the genetic affinity of the samples towards human reference genome. Through solving one of the most challenging biases in data analysis, so-called reference bias, genotype imputation using Glimpse v2 is promising for low coverage ancient human genomic data analysis and for rare-variant-based and haplotype-based analysis.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"461-473"},"PeriodicalIF":2.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Revealing the key role of cuproptosis in osteoporosis via the bioinformatic analysis and experimental validation of cuproptosis-related genes. 通过对杯突症相关基因的生物信息学分析和实验验证，揭示杯突症在骨质疏松症中的关键作用。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2024-09-01 Epub Date: 2024-06-21 DOI: 10.1007/s00335-024-10049-0

Jianxing Chen, Qifeng Sun, Yi Wang, Wenzhe Yin

{"title":"Revealing the key role of cuproptosis in osteoporosis via the bioinformatic analysis and experimental validation of cuproptosis-related genes.","authors":"Jianxing Chen, Qifeng Sun, Yi Wang, Wenzhe Yin","doi":"10.1007/s00335-024-10049-0","DOIUrl":"10.1007/s00335-024-10049-0","url":null,"abstract":"The incidence of osteoporosis has rapidly increased owing to the ageing population. Cuproptosis, a novel mechanism that regulates cell death, may be a new therapeutic approach. However, the relevance of cuproptosis in the immune microenvironment and osteoporosis immunotherapy is still unknown. We intersected the differentially expressed genes from osteoporotic samples with 75 cuproptosis-related genes to identify 16 significantly expressed cuproptosis genes. We further explored the connection between the cuproptosis pattern, immune microenvironment, and immunotherapy. The weighted gene co-expression network analysis algorithm was used to identify cuproptosis phenotype-associated genes, and we used quantitative real-time PCR and immunohistochemistry in mouse femur tissues to verify hub gene (MAP2K2, FDX1, COX19, VEGFA, CDKN2A, and NFE2L2) expression. Six hub genes and 59 cuproptosis phenotype-associated genes involved in immunisation were identified among the osteoporosis and control groups, and the majority of these 59 genes were enriched in the inflammatory response, as well as in signal transducers, Janus kinase, and transcription pathway activators. In addition, two different clusters of cuproptosis were found, and immune infiltration analysis showed that gene Cluster 1 had a greater immune score and immune infiltration level. Further analysis revealed that three key genes (COX19, MAP2K2, and FDX1) were highly correlated with immune cell infiltration, and external experiments validated the association of these three genes with the prognosis of osteoporosis. We used the three key mRNAs COX19, MAP2K2, and FDX1 as a classification model that may systematically elucidate the complex connection between cuproptosis and the immune microenvironment of osteoporosis. New insights into osteoporosis pathogenesis and immunotherapy prospects may be gained from this study.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"414-431"},"PeriodicalIF":2.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The expression profile of brain-derived exosomal miRNAs reveals the key molecules responsible for spontaneous motor function recovery in a rat model with permanent middle cerebral artery occlusion. 脑源性外泌体 miRNAs 的表达谱揭示了导致永久性大脑中动脉闭塞大鼠模型自发运动功能恢复的关键分子。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2024-09-01 Epub Date: 2024-07-12 DOI: 10.1007/s00335-024-10052-5

Liuyu Liu, Shengri Chen, Shuolin Liang, Zhijian Liang

{"title":"The expression profile of brain-derived exosomal miRNAs reveals the key molecules responsible for spontaneous motor function recovery in a rat model with permanent middle cerebral artery occlusion.","authors":"Liuyu Liu, Shengri Chen, Shuolin Liang, Zhijian Liang","doi":"10.1007/s00335-024-10052-5","DOIUrl":"10.1007/s00335-024-10052-5","url":null,"abstract":"The analysis of alterations in the expression and functionality of brain-derived exosomal miRNAs within ischemic stroke lesions provides significant insights into the mechanisms that contribute to disease recovery. We assessed spontaneous motor function in a rat model of permanent middle cerebral artery occlusion (pMCAO) using motor function scores and magnetic resonance imaging (MRI). Brain-derived exosomes from the infarcted brain tissue of the animal model were extracted and high-throughput sequencing of them was performed followed by bioinformatics analysis for differentially expressed miRNAs target genes. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to measure expression levels of differentially expressed miRNAs at various time points. The oxygen-glucose deprivation (OGD) model was established to investigate gene function through the assessment of cell proliferation and apoptosis using EdU proliferation and JC-1 apoptosis assay. The rat model demonstrated a spontaneous recovery of motor function and a reduction in cerebral infarction area from day 1 to day 14 post-operation. Over the course of the recovery period, miR-24-3p, miR-129-1-3p, and miR-212-5p maintained consistent expression levels, reaching their peak on the initial day following surgery. In the cell model, EdU detection indicated that miR-129-1-3p promoted cellular proliferation, while JC-1 detection revealed its suppressive impact on cellular apoptosis. The current research findings indicated the presence of spontaneous motor function restoration in a rat model of ischemic stroke. MiR-24-3p, miR-129-1-3p, and miR-212-5p were identified as pivotal genes in this recovery process, with miR-129-1-3p potentially influencing the restoration of spontaneous motor function in ischemic stroke through the regulation of neuronal proliferation and apoptosis.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"362-376"},"PeriodicalIF":2.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141600333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Generation of a humanized mAce2 and a conditional hACE2 mouse models permissive to SARS-COV-2 infection. 产生允许感染 SARS-COV-2 的人源化 mAce2 和条件性 hACE2 小鼠模型。

IF 2.5 4区生物学

Mammalian Genome Pub Date : 2024-06-01 Epub Date: 2024-03-15 DOI: 10.1007/s00335-024-10033-8

I-Wen Song, Megan Washington, Carolina Leynes, Jason Hsu, Kempaiah Rayavara, Yangjin Bae, Nele Haelterman, Yuqing Chen, Ming-Ming Jiang, Aleksandra Drelich, Vivian Tat, Denise G Lanza, Isabel Lorenzo, Jason D Heaney, Chien-Te Kent Tseng, Brendan Lee, Ronit Marom

{"title":"Generation of a humanized mAce2 and a conditional hACE2 mouse models permissive to SARS-COV-2 infection.","authors":"I-Wen Song, Megan Washington, Carolina Leynes, Jason Hsu, Kempaiah Rayavara, Yangjin Bae, Nele Haelterman, Yuqing Chen, Ming-Ming Jiang, Aleksandra Drelich, Vivian Tat, Denise G Lanza, Isabel Lorenzo, Jason D Heaney, Chien-Te Kent Tseng, Brendan Lee, Ronit Marom","doi":"10.1007/s00335-024-10033-8","DOIUrl":"10.1007/s00335-024-10033-8","url":null,"abstract":"The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) remains a public health concern and a subject of active research effort. Development of pre-clinical animal models is critical to study viral-host interaction, tissue tropism, disease mechanisms, therapeutic approaches, and long-term sequelae of infection. Here, we report two mouse models for studying SARS-CoV-2: A knock-in mAce2F83Y,H353K mouse that expresses a mouse-human hybrid form of the angiotensin-converting enzyme 2 (ACE2) receptor under the endogenous mouse Ace2 promoter, and a Rosa26 conditional knock-in mouse carrying the human ACE2 allele (Rosa26hACE2). Although the mAce2F83Y,H353K mice were susceptible to intranasal inoculation with SARS-CoV-2, they did not show gross phenotypic abnormalities. Next, we generated a Rosa26hACE2;CMV-Cre mouse line that ubiquitously expresses the human ACE2 receptor. By day 3 post infection with SARS-CoV-2, Rosa26hACE2;CMV-Cre mice showed significant weight loss, a variable degree of alveolar wall thickening and reduced survival rates. Viral load measurements confirmed inoculation in lung and brain tissues of infected Rosa26hACE2;CMV-Cre mice. The phenotypic spectrum displayed by our different mouse models translates to the broad range of clinical symptoms seen in the human patients and can serve as a resource for the community to model and explore both treatment strategies and long-term consequences of SARS-CoV-2 infection.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"113-121"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140136963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of important gene signatures in schizophrenia through feature fusion and genetic algorithm. 通过特征融合和遗传算法识别精神分裂症的重要基因特征。

IF 2.5 4区生物学

Mammalian Genome Pub Date : 2024-06-01 Epub Date: 2024-03-21 DOI: 10.1007/s00335-024-10034-7

Zhixiong Chen, Ruiquan Ge, Changmiao Wang, Ahmed Elazab, Xianjun Fu, Wenwen Min, Feiwei Qin, Gangyong Jia, Xiaopeng Fan

{"title":"Identification of important gene signatures in schizophrenia through feature fusion and genetic algorithm.","authors":"Zhixiong Chen, Ruiquan Ge, Changmiao Wang, Ahmed Elazab, Xianjun Fu, Wenwen Min, Feiwei Qin, Gangyong Jia, Xiaopeng Fan","doi":"10.1007/s00335-024-10034-7","DOIUrl":"10.1007/s00335-024-10034-7","url":null,"abstract":"Schizophrenia is a debilitating psychiatric disorder that can significantly affect a patient's quality of life and lead to permanent brain damage. Although medical research has identified certain genetic risk factors, the specific pathogenesis of the disorder remains unclear. Despite the prevalence of research employing magnetic resonance imaging, few studies have focused on the gene level and gene expression profile involving a large number of screened genes. However, the high dimensionality of genetic data presents a great challenge to accurately modeling the data. To tackle the current challenges, this study presents a novel feature selection strategy that utilizes heuristic feature fusion and a multi-objective optimization genetic algorithm. The goal is to improve classification performance and identify the key gene subset for schizophrenia diagnostics. Traditional gene screening techniques are inadequate for accurately determining the precise number of key genes associated with schizophrenia. Our innovative approach integrates a filter-based feature selection method to reduce data dimensionality and a multi-objective optimization genetic algorithm for improved classification tasks. By combining the filtering and wrapper methods, our strategy leverages their respective strengths in a deliberate manner, leading to superior classification accuracy and a more efficient selection of relevant genes. This approach has demonstrated significant improvements in classification results across 11 out of 14 relevant datasets. The performance on the remaining three datasets is comparable to the existing methods. Furthermore, visual and enrichment analyses have confirmed the practicality of our proposed method as a promising tool for the early detection of schizophrenia.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"241-255"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140184825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic factors underlying host resistance to Rhipicephalus microplus tick infestation in Braford cattle: a systems biology perspective. 布拉福德牛宿主对 Rhipicephalus microplus 蜱虫侵扰抵抗力的遗传因素：系统生物学视角。

IF 2.5 4区生物学

Mammalian Genome Pub Date : 2024-06-01 Epub Date: 2024-03-13 DOI: 10.1007/s00335-024-10030-x

Wanessa A Carvalho, Emanuelle B Gaspar, Robert Domingues, Luciana C A Regitano, Fernando F Cardoso

{"title":"Genetic factors underlying host resistance to Rhipicephalus microplus tick infestation in Braford cattle: a systems biology perspective.","authors":"Wanessa A Carvalho, Emanuelle B Gaspar, Robert Domingues, Luciana C A Regitano, Fernando F Cardoso","doi":"10.1007/s00335-024-10030-x","DOIUrl":"10.1007/s00335-024-10030-x","url":null,"abstract":"Approximately 80% of the world's cattle are raised in regions with a high risk of tick-borne diseases, resulting in significant economic losses due to parasitism by Rhipicephalus (Boophilus) microplus. However, the lack of a systemic biology approach hampers a comprehensive understanding of tick-host interactions that mediate tick resistance phenotypes. Here, we conducted a genome-wide association study (GWAS) of 2933 Braford cattle and found 340 single-nucleotide polymorphisms (SNPs) associated with tick counts. Gene expression analyses were performed on skin samples obtained from previously tick-exposed heifers with extremely high or low estimated breeding values for R. microplus counts. Evaluations were performed both before and after artificial infestation with ticks. Differentially expressed genes were found within 1-Mb windows centered at significant SNPs from GWAS. A total of 330 genes were related to the breakdown of homeostasis that was induced by larval attachment to bovine skin. Enrichment analysis pointed to a key role of proteolysis and signal transduction via JAK/STAT, NFKB and WNT/beta catenin signaling pathways. Integrative analysis on matrixEQTL revealed two cis-eQTLs and four significant SNPs in the genes peptidyl arginine deiminase type IV (PADI4) and LOC11449251. The integration of genomic data from QTL maps and transcriptome analyses has identified a set of twelve key genes that show significant associations with tick loads. These genes could be key candidates to improve the accuracy of genomic predictions for tick resistance in Braford cattle.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"186-200"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140119945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pyroptosis is involved in the immune microenvironment regulation of unexplained recurrent miscarriage. 脓毒症参与了不明原因复发性流产的免疫微环境调控。

IF 2.5 4区生物学

Mammalian Genome Pub Date : 2024-06-01 Epub Date: 2024-03-27 DOI: 10.1007/s00335-024-10038-3

Jing Wang, Uskenbayeva Nuray, Hongchao Yan, Yang Xu, Lisha Fang, Ranran Li, Xin Zhou, Hong Zhang

{"title":"Pyroptosis is involved in the immune microenvironment regulation of unexplained recurrent miscarriage.","authors":"Jing Wang, Uskenbayeva Nuray, Hongchao Yan, Yang Xu, Lisha Fang, Ranran Li, Xin Zhou, Hong Zhang","doi":"10.1007/s00335-024-10038-3","DOIUrl":"10.1007/s00335-024-10038-3","url":null,"abstract":"Unexplained recurrent miscarriage (URM) is a common pregnancy complication with few effective therapies. Moreover, little is known regarding the role of pyroptosis in the regulation of the URM immune microenvironment. To address this issue, gene expression profiles of publicly available placental datasets GSE22490 and GSE76862 were downloaded from the Gene Expression Omnibus database. Pyroptosis-related differentially expressed genes were identified and a total of 16 differentially expressed genes associated with pyroptosis were detected, among which 1 was upregulated and 15 were downregulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that the functionally enriched modules and pathways of these genes are closely related to immune and inflammatory responses. Four hub genes were identified: BTK, TLR8, NLRC4, and TNFSF13B. BTK, TLR8, and TNFSF13B were highly connected with immune cells, according to the correlation analysis of four hub genes and 20 different types of immune cells (p < 0.05). The four hub genes were used as research objects to construct the interaction networks. Chorionic villus tissue was used for quantitative real-time polymerase chain reaction and western blot to confirm the expression levels of hub genes, and the results showed that the expression of the four hub genes was significantly decreased in the chorionic villus tissue in the URM group. Collectively, the present study indicates that perhaps pyroptosis is essential to the diversity and complexity of the URM immune microenvironment, and provides a theoretical basis and research ideas for subsequent target gene verification and mechanism research.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"256-279"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140306148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0