Comparative and Functional Genomics最新文献

{"title":"A Study to Evaluate the Potential Role and Clinical Application Value of Long Noncoding RNA CASC Family Members in Colorectal Cancer Based on Transcriptomic Data","authors":"Chao Liang,&nbsp;Jun Wang,&nbsp;Xinyu Liu","doi":"10.1155/ijog/3881424","DOIUrl":"10.1155/ijog/3881424","url":null,"abstract":"<p><b>Background:</b> Long noncoding RNA (lncRNA) CASC, crucial in colorectal cancer (CRC) progression, remains largely unexplored despite its potential.</p><p><b>Methods:</b> The CRC data comes from The Cancer Genome Atlas (TCGA) database. The limma package was used to screen differentially expressed genes (DEGs), intersecting with CASC genes that yielded key hub lncRNAs. Next, the lncRNA–protein interaction network was developed applying Cytoscape software. The association between immune cell infiltration and lncRNAs was calculated using the ESTIMATE package, CIBERSORT package, and ssGSEA. Based on the survminer package to assess the correlation between hub gene expression levels and clinicopathologic features of CRC patients, cellular models were utilized to assess the mRNA expression levels and potential biological functions of the screened markers.</p><p><b>Results:</b> We filtered 2326 DEGs that were notably enriched in pathways related to metastasis, cell growth, and EMT. This study found six hub lncRNAs (CASC15, CASC16, CASC8, CASC9, CASC19, and CASC18) showed a high diagnostic accuracy, with the area under the curve (AUC) values all exceeding 0.7. There were 44 proteins in the lncRNA–protein interaction network that interact with hub lncRNAs, among which both LIN28B and IGF2BP2 interact with six hub lncRNAs. Immune infiltration analysis indicated that the six hub lncRNAs were significantly correlated with the multiple types of immune cells. Pathological analysis demonstrated that the expression of CASC15 elevated with the progression of TNM staging. Cellular assays had revealed that all are significantly associated with CRC; particularly, CASC15 knockdown repressed the in vitro metastasis of CRC cells.</p><p><b>Conclusion:</b> We constructed and validated a robust signature of six lncRNA CASC for predicting survival of CRC patients and characterizing the immune infiltration landscape. These results reveal that the CASC gene family could be a therapeutic target for CRC patients.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/3881424","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole Exome Sequencing Identified a Stop-Gained Mutation in DYSF Gene Associated With Dysferlinopathy in an Iranian Family","authors":"Saba Baghshomali,&nbsp;Asiyeh Jebelli,&nbsp;Mina Kazemzadeh,&nbsp;Farzaneh Jalalypour,&nbsp;Mohammad Yazdchi,&nbsp;Amir Ali Mokhtarzadeh,&nbsp;Leila Emrahi","doi":"10.1155/ijog/9103068","DOIUrl":"10.1155/ijog/9103068","url":null,"abstract":"<p><b>Introduction:</b> Muscular dystrophy (MD) refers to a group of hereditary disorders characterized by progressive muscle degeneration, often caused by a deficiency or insufficient levels of glycoproteins in muscle cell membranes. Mutations in various genes lead to different types of MD, each with distinct clinical manifestations and inheritance patterns. The genetic heterogeneity of MD complicates the identification of the causative genes.</p><p><b>Materials and Methods:</b> This research was conducted to identify the genetic basis of MD in an Iranian family with three affected members. Whole exome sequencing (WES) was performed on a proband who had initially been misdiagnosed with polymyositis. Following the identification of the disease-causing variant via WES, cosegregation analysis was carried out among two affected siblings, the asymptomatic parents, and one unaffected sibling.</p><p><b>Results:</b> WES identified a homozygous nonsense variant (c.6001C&gt;T, p.Gln2001Ter) in Exon 53 of the <i>DYSF</i> gene, which encodes dysferlin, a transmembrane protein essential for membrane protection and repair following damage. This stop-gain mutation results in a nonfunctional truncated protein lacking the transmembrane helix, preventing its anchorage to the membrane. Dysfunction of dysferlin is associated with limb–girdle muscular dystrophy 2B (LGMD2B) and Miyoshi myopathy.</p><p><b>Discussion:</b> Bioinformatics analyses and clinical findings confirmed the pathogenicity of this variant in a homozygous state, consistent with autosomal recessive inheritance. Furthermore, structural modeling suggested that the mutation significantly disrupts the tertiary structure of dysferlin. Since the disorder onset in the proband and his two affected sisters began in the proximal limb muscles, the condition was classified as LGMD. The study highlights the diagnostic value of WES in accurately identifying disease-causing variants, offering substantial improvements in time and cost efficiency over conventional diagnostic procedures.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/9103068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Basis of Aggressiveness in Pituitary Adenomas and Its Association With the Immune Microenvironment","authors":"Xiaoyan Chen,&nbsp;Jingnan Wang,&nbsp;Qianqian Guo","doi":"10.1155/ijog/9346050","DOIUrl":"10.1155/ijog/9346050","url":null,"abstract":"<p><b>Background:</b> Pituitary adenomas (PAs) are common intracranial tumors, and their aggressive phenotype exhibits a poor prognosis. We aimed to explore the aggressive feature of PAs and discover novel diagnostic markers.</p><p><b>Method:</b> The datasets of GSE260487 and GSE169498, which contained invasive and noninvasive samples, were downloaded from the Gene Expression Omnibus (GEO) database. Aggressive phenotype-related gene modules were classified using the “WGCNA” package. Differentially expressed genes (DEGs) in each module were identified by the “limma” package. Next, a protein–protein interaction (PPI) network was used in the construction and identification process of key genes, and the CytoHubba tool was utilized to analyze the subnetwork and select the top 10 genes. Diagnostic markers were selected using two machine learning algorithms: support vector machine (SVM) and Lasso. Finally, the ESTIMATE and “GSVA” were applied for immune infiltration assessment.</p><p><b>Results:</b> WGCNA showed that the turquoise module was closely associated with the aggressive phenotype and enriched in neural differentiation and cell migration pathways. A total of 521 DEGs were intersected with the turquoise module genes to obtain 187 overlapping genes, from which 10 hub genes related to tumor proliferation were selected to develop a PPI network. Next, we determined <i>MYH7</i> as an accurate diagnostic marker, and the immune infiltration analysis revealed that <i>MYH7</i> expression was negatively correlated with stromal score and immune score but positively correlated with the infiltration of antitumor cells.</p><p><b>Conclusion:</b> We developed a novel marker with a strong diagnostic performance for PAs, providing novel insights for the detection and individualized treatment of PAs.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/9346050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distribution of Methylene Tetrahydrofolate Reductase Gene Polymorphisms in Women of Childbearing Age in Tai’an","authors":"Bo Zhou,&nbsp;Chengzhen Gao,&nbsp;Lirong Chen,&nbsp;Yumei Wang,&nbsp;Shufang Zhang,&nbsp;Chao Hou,&nbsp;Xiangyang An","doi":"10.1155/ijog/8889232","DOIUrl":"10.1155/ijog/8889232","url":null,"abstract":"<p><b>Objective:</b> The objective was to explore the distribution characteristics of methylenetetrahydrofolate reductase <i>MTHFR</i> 677C &gt; T and 1298A &gt; C gene polymorphisms among women of childbearing age in the Tai’an area.</p><p><b>Method:</b> A total of 243 women of childbearing age, the age ranged from 20 to 46 years, with a mean age of 31.0 ± 5.1 years, attending the Eugenics Clinic of Tai’an City Central Hospital between January 2018 and April 2019 were selected. The <i>MTHFR</i> 677C &gt; T and 1298A &gt; C gene polymorphisms were determined by fluorescence in situ hybridization.</p><p><b>Result:</b> Among 243 women of childbearing age, the <i>MTHFR</i> 677C &gt; T genotype frequencies of CC, CT, and TT were 14.4%, 44.9%, and 40.7%, respectively, and the C and T Allele frequencies were 36.8% and 63.2%, respectively. The <i>MTHFR</i> 1298A &gt; C genotype frequencies of AA, AC, and CC were 77.0%, 21.0%, and 2.0%, respectively. The A and C allele frequencies were 87.4% and 12.6%, respectively. The proportions of CC/AA, CC/AC, CC/CC, CT/AA, CT/AC, TT/AA, and TT/AC were 6.6%, 5.8%, 2.0%, 30.5%, 14.4%, 39.9%, and 0.8%. The proportion of women at moderate or severe risk of folic acid metabolism reached 87.6%. The <i>MTHFR</i> 677C &gt; T gene mutation rate has obvious regional characteristics.</p><p><b>Conclusion:</b> The <i>MTHFR</i> 677C &gt; T and 1298A &gt; C gene polymorphisms in Tai’an were obvious. About 87.6% of women of childbearing age were at medium or high risk of folic acid utilization.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/8889232","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Biomarkers Based on Starvation Response-Related Genes for Assessing the Immune Profile and Prognosis in Lung Adenocarcinoma","authors":"Xixian Lou,&nbsp;Hui Xia,&nbsp;Zongxiao Shangguan,&nbsp;Lianmin Bao,&nbsp;Heping Lin","doi":"10.1155/ijog/9950674","DOIUrl":"10.1155/ijog/9950674","url":null,"abstract":"<p><b>Background:</b> Lung adenocarcinoma (LUAD) exhibits a high recurrence rate and an unfavorable prognosis. The role of the starvation-induced tumor microenvironment (TME), which is closely linked to metabolism, remains poorly understood in LUAD.</p><p><b>Methods:</b> LUAD patient samples were collected from public databases, and starvation response-related genes (SRRGs) were acquired from the MSigDB database. As starvation response may enhance autophagy in cancer cells, the Human Autophagy Database (HADb) was accessed to collect autophagy-related genes (ARGs). Next, the association between the expressions of ARGs and SRRGs was analyzed applying Pearson’s algorithm. The SRRG score was calculated by GSVA package for each sample, and WGCNA package was utilized to screen SRRG-related module genes. Differentially expressed lncRNAs between LUAD and control samples were screened by the limma package. Subsequently, the lncRNAs associated with SRRG-related module genes were intersected with differentially expressed lncRNAs to obtain key SRRG-correlated lncRNAs. The number of key lncRNAs in the risk model was optimized by performing univariate and multivariate Cox regression analyses. Next, immune profiling between different LUAD risk groups was conducted using single-sample GSEA (ssGSEA), MCP-counter, and ESTIMATE algorithms. The Mutect2 software and clusterProfiler R package were employed to analyze the mutation profiles and pathway enrichment of patients in different risk groups, respectively. In addition, the expressions of key lncRNAs in LUAD cells were verified by qRT-PCR, and the migratory and invasive capabilities of the cells were measured by wound healing and transwell assays.</p><p><b>Results:</b> We identified 162 potential SRRGs linked to autophagy, glycolysis, and starvation responses. In addition, 102 candidate SRRG-related lncRNAs were selected from SRRG-related module genes. Three key SRRG-related lncRNAs (AC023421.1, AL034397.3, and LINC01537) were screened for developing an accurate risk model. Notably, the high-risk group showed a significantly higher mutation rate and oncogenic pathway scores and markedly worse immune infiltration and overall survival (OS). In vitro experiments revealed that LINC01537 was highly expressed in A549 cells, and that after knockdown of LINC01537, the migration and invasion of LUAD cells were suppressed.</p><p><b>Conclusion:</b> This study identified three key lncRNAs related to starvation response and created a risk model that can accurately assess the prognosis and immune characteristics in LUAD, offering novel biomarkers and a theoretical basis for the precision immunotherapy and targeted intervention in LUAD.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/9950674","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Different Components of Buyang Huanwu Tang on the PPARγ/LXRα/ABCA1 Pathway in Hypercholesterolemia Mouse Model","authors":"Shuaihu Yang,&nbsp;Yukun Zhang,&nbsp;Xinxin Liu,&nbsp;Xingtong Chen,&nbsp;Yuxue Ma,&nbsp;Shijian Fang,&nbsp;Ruihong Yang,&nbsp;Jinbiao Yang,&nbsp;Yunyue Zhou,&nbsp;Xiao He,&nbsp;Pengcheng Li,&nbsp;Hongbin Xiao,&nbsp;Wenying Niu","doi":"10.1155/ijog/9595757","DOIUrl":"10.1155/ijog/9595757","url":null,"abstract":"<p>The aim of this study is to compare the effects of different components of Buyang Huanwu Tang (BYHWT) on the peroxisome proliferator-activated receptor <i>γ</i> (PPAR<i>γ</i>)/liver X receptor <i>α</i> (LXR<i>α</i>)/ATP-binding cassette transporter A1 (ABCA1) pathway and its lipid-lowering effects. This study shows that the BYHWT alcohol precipitation and 75% alcohol components can significantly reduce the serum levels of triglycerides (TGs), low-density lipoprotein (LDL), cholesterol (CHO), and hepatic function damage indicators such as glutamic oxaloacetic transaminase (AST) and glutamic pyruvic transaminase (ALT) in hypercholesterolemia mouse model. After treatment, the presence of lipid droplets in liver cells was reduced, and the destruction of adipocytes was improved. The Western blot (WB) results showed that alcohol precipitation and 75% alcohol components can upregulate PPAR<i>γ</i>, ABCA1, and LXR<i>α</i>. The expression of these components indicates that PPAR<i>γ</i> upregulation can activate LXR<i>α</i>, thus regulating the expression of ABCA1, mediating CHO efflux, promoting reverse cholesterol transport (RCT), and regulating the downstream gene CYP7A1 to participate in bile acid synthesis and metabolism. In summary, the experimental results indicate that the BYHWT alcohol precipitation, 50% alcohol, and 75% alcohol components can modulate the PPAR<i>γ</i>/LXR<i>α</i>/ABCA1 pathway in hypercholesterolemia mouse model to promote CHO metabolism.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/9595757","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144589675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cooling Blood and Detoxicating Formula Treats Psoriasis Through RHCG-Related Mechanisms","authors":"Qian Zhang,&nbsp;Juan Huang,&nbsp;Cheng-cheng Feng,&nbsp;Yuan-jie Liu,&nbsp;Ning Yang,&nbsp;Xi Zou,&nbsp;Chen Ji,&nbsp;Shun Guo,&nbsp;Hui Shen","doi":"10.1155/ijog/5132158","DOIUrl":"10.1155/ijog/5132158","url":null,"abstract":"<p>This study explores the therapeutic potential of the cooling blood and detoxicating formula (CBDF) in the treatment of psoriasis, emphasizing its anti-inflammatory properties and its interaction with RHCG-related mechanisms. Psoriasis, a complex skin disorder characterized by abnormal keratinocyte proliferation and immune system dysregulation, remains challenging to treat effectively. Utilizing advanced techniques including network pharmacology, single-cell RNA sequencing (scRNA-seq), and spatial transcriptomics, this research identifies key active components in CBDF—quercetin and kaempferol—that influence critical inflammatory pathways. In experimental models, CBDF significantly alleviates psoriasis symptoms, reducing keratinocyte differentiation abnormalities and dendritic cell (DC) activation. Molecular docking studies demonstrate strong interactions between RHCG and the active ingredients in CBDF. These findings suggest that CBDF exerts its effects through a multifaceted approach, with RHCG identified as a pivotal target. While the results are promising, further clinical validation and mechanistic research are needed. This study underscores the potential of CBDF as a treatment for psoriasis, blending traditional medicine with modern molecular insights.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/5132158","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FENDRR Affects COAD Biological Behavior by Inhibiting the DUSP4/CREB/PRKACB Pathway","authors":"Hao Zhang,&nbsp;Li Hong,&nbsp;Zirui Zhuang,&nbsp;Qiange Zhang,&nbsp;Feng Zhang,&nbsp;Ruipeng Wang,&nbsp;Jinjing Xu,&nbsp;Youyuan Tang,&nbsp;Xingpo Guo,&nbsp;Ling Gao","doi":"10.1155/ijog/2765511","DOIUrl":"10.1155/ijog/2765511","url":null,"abstract":"<p><b>Background:</b> Colorectal cancer (CRC) is acknowledged as the third leading cause of cancer-related mortality, attributed to its high incidence and fatality rates. Long noncoding RNAs (lncRNAs) have emerged as novel biomarkers for the treatment of colon adenocarcinoma. This study is aimed at investigating the function and underlying mechanisms of the lncRNA fetal-lethal noncoding developmental regulatory RNA (FENDRR) in regulating the malignant phenotype of CRC (COAD) cells.</p><p><b>Methods:</b> This investigation examined FENDRR expression patterns and their association with clinical outcomes in 496 COAD and 173 READ patients from The Cancer Genome Atlas (TCGA) dataset. Additionally, 10 clinical COAD specimens were collected to validate FENDRR expression levels. Using lentiviral-mediated gene delivery, we stably upregulated FENDRR in HCT-116 cells, with transcriptional changes quantified via qPCR. The tumor biological behavior was evaluated using in vitro experiments, including CCK-8, colony formation, wound healing, transwell assays, and immunofluorescence staining. Protein-level alterations were subsequently confirmed by Western blot.</p><p><b>Results:</b> Through bioinformatics evaluation, a notable decrease in FENDRR expression levels was observed in both COAD and READ tissues, with a pronounced link between FENDRR expression and tumor T stage classification in COAD cases. Patients exhibiting diminished FENDRR expression showed worse clinical outcomes in COAD. Enrichment analysis demonstrated significant associations between FENDRR and various signaling cascades, particularly the cAMP pathway. Additionally, immune cell infiltration analysis showed a significant association with FENDRR expression levels. In vitro experiments confirmed that FENDRR overexpression hindered the proliferation, migration, and invasion of cells. Mechanistically, FENDRR has been demonstrated to induce the sinking of the DUSP4/CREB/PRKACB signaling pathway and reverse the epithelial–mesenchymal transition (EMT) pathway, thereby inhibiting tumor growth.</p><p><b>Conclusion:</b> We establish FENDRR as a tumor-suppressing gene that plays a significant role in suppressing the advancement and metastatic spread of COAD. These findings underscore its diagnostic and prognostic utility in COAD.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/2765511","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Genetic Basis of Ketosis: Preliminary GWAS Findings on Beta-Hydroxybutyrate Levels in Holstein Cattle","authors":"Veysel Bay","doi":"10.1155/ijog/5520648","DOIUrl":"10.1155/ijog/5520648","url":null,"abstract":"<p>Ketosis is a metabolic condition characterized by a shift in energy metabolism, occurring when glucose availability is depleted and fat becomes the alternative primary energy source, resulting in the accumulation of ketone bodies. In dairy cattle, ketosis represents a significant challenge, adversely affecting both animal health and farm productivity. The genetic basis of ketosis in cattle has attracted increasing attention, with genome-wide association studies (GWAS) emerging as a crucial method for identifying relevant genetic factors. This study was aimed at investigating genome-wide regions associated with beta-hydroxybutyrate (BHB) concentrations in Holstein–Friesian cows’ blood before calving in the United Kingdom. BHB measurement data from 253 previously genotyped cows were used in the analyses. The results revealed five significant SNPs on Chromosome 15 (BTA15) and one significant SNP on BTA5 (<i>p</i> &lt; 1.60e − 6). Notably, the SNPs on BTA15 clustered within a genomic region enriched with genes implicated in lipid metabolism and energy balance, highlighting its potential role in ketosis susceptibility. These preliminary findings refine the genetic architecture of ketosis and offer new avenues for improving dairy cattle health and welfare through targeted genetic selection programs while highlighting the need for validation in larger and independent populations.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/5520648","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating Overlapping Genetic Factors and Novel Causal Genes in Autoimmune Diseases: A Transcriptome-Wide Association and Multiomics Study","authors":"Leihua Fu,&nbsp;Jieni Yu,&nbsp;Xin Wang,&nbsp;Zhe Chen,&nbsp;Jiaying Sun,&nbsp;Feidan Gao,&nbsp;Zhijian Zhang,&nbsp;Jiaping Fu,&nbsp;Pan Hong,&nbsp;Weiying Feng","doi":"10.1155/ijog/9595651","DOIUrl":"10.1155/ijog/9595651","url":null,"abstract":"<p><b>Background:</b> Autoimmune diseases exhibit familial clustering and co-occurrence, suggesting the presence of shared genetic risk factors. However, the overlapping genetic factors across these diseases have yet to be fully elucidated. This study aimed to identify shared genetic factors across five autoimmune diseases: systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), Sjögren’s syndrome (SS), and polymyalgia rheumatica (PMR).</p><p><b>Methods:</b> A blood tissue–based transcriptome-wide association study (TWAS) was conducted to identify candidate genes. Bayesian colocalization analysis was employed to pinpoint genetic variants shared across diseases. Multiomics summary data–based Mendelian randomization (SMR) was used to identify causal risk genes, while transcriptomic analysis, gene set variation analysis (GSVA), and weighted gene coexpression network analysis (WGCNA) were applied to further investigate the functional roles of these genes.</p><p><b>Results:</b> The TWAS identified 78 candidate genes across the five autoimmune diseases. Bayesian colocalization analysis revealed five genes, GTF2H4, FLOT1, HCP5, IER3, and STK19, that share genetic variants across these disorders. Specifically, RA and AS shared independent variants of GTF2H4 (rs2230365 and rs147708689, respectively). HCP5 variants were shared with SS (rs1800628) and SLE (rs1150757), and rs1800628 was also identified as a shared locus in FLOT1 for SLE. SMR analysis highlighted FLOT1 as a strong causal risk gene for SLE. Transcriptomic analysis showed that FLOT1 is highly expressed in T cells and platelets, with involvement in multiple metabolic pathways. WGCNA identified four key neighboring genes, EHD1, SLC10A3, LMNA, and STXBP2, associated with FLOT1.</p><p><b>Conclusion:</b> This study uncovers shared genetic factors across five autoimmune diseases, with FLOT1 identified as a novel causal risk gene for SLE. These findings suggest that platelet-mediated pathogenic mechanisms may contribute to SLE, providing a potential target for future therapeutic interventions.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/9595651","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}