Mammalian Genome最新文献

{"title":"Integrative approaches to m6A and m5C RNA modifications in autism spectrum disorder revealing potential causal variants.","authors":"Syed Mansoor Jan, Aamir Fahira, Eman S G Hassan, Ali Saber Abdelhameed, Dongqing Wei, Abdul Wadood","doi":"10.1007/s00335-024-10095-8","DOIUrl":"https://doi.org/10.1007/s00335-024-10095-8","url":null,"abstract":"<p><p>Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that currently affects approximately 1-2% of the global population. Genome-wide studies have identified several loci associated with ASD; however, pinpointing causal variants remains elusive. Therefore, functional studies are essential to discover potential therapeutics for ASD. RNA modification plays a crucial role in the post-transcriptional regulation of mRNA, with m6A and m5C being the most prevalent internal modifications. Recent research indicates their involvement in the regulation of key genes associated with ASD. In this study, we conducted an integrative genomic analysis of ASD, incorporating m6A and m5C variants, followed by cis-eQTL, gene differential expression, and gene enrichment analyses to identify causal variants from a genome-wide study of ASD. We identified 20,708 common m6A-SNPs and 2,407 common m5C-SNPs. Among these, 647 m6A-SNPs exhibited cis-eQTL signals with a p-value < 0.05, while only 81 m5C-SNPs with a p-value < 0.05 showed cis-eQTL signals. Most of these were functional loss variants, with 38 variants representing the most significant common m6A/m5C-SNPs associated with key ASD-related genes. In the gene differential expression analysis, seven proximal genes corresponding to significant m6A/m5C-SNPs were differentially expressed in at least one of the three microarray gene expression profiles of ASD. Key differentially expressed genes corresponding to m6A/m5C cis-variants included KIAA1671 (rs5752063, rs12627825), INTS1 (rs67049052, rs10237910), VSIG10 (rs7965350), TJP2 (rs3812536), FAM167A (rs9693108), TMEM8A (rs1802752), and NUP43 (rs3924871, rs7818, rs9383844, rs9767113). Cell-specific cis-eQTL analysis for proximal gene identification, combined with gene expression datasets from single-cell RNA-seq analysis, would validate the causal relationship of gene regulation in brain-specific regions, and experimental validation in cell lines would achieve the goal of precision medicine.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909950","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}

{"title":"Understanding PACS2 syndrome's pathomechanism by studying E209K and E211K mutations.","authors":"Arkadiusz Zbikowski, Tomasz Kowalczyk, Petr Kasparek, Jan Prohazka, Radislav Sedlacek, Michał Ciborowski, Dominik Cysewski, Kacper Łukasiewicz","doi":"10.1007/s00335-024-10098-5","DOIUrl":"https://doi.org/10.1007/s00335-024-10098-5","url":null,"abstract":"<p><p>Phosphofurin acidic cluster sorting protein 2 (PACS2) plays a vital role in maintaining cellular homeostasis by regulating protein trafficking between cellular membranes. This function impacts crucial processes like apoptosis, mitochondria-endoplasmic reticulum interaction, and subsequently Ca²⁺ flux, lipid biosynthesis, and autophagy. Missense mutations, particularly E209K and E211K, are linked to developmental and epileptic encephalopathy-66 (DEE66), known as PACS2 syndrome. Individuals with this syndrome exhibit neurodevelopmental delay, seizures, facial dysmorphism, hypotonia, and delayed motor skills.Understanding the impact of these missense mutations on molecular processes is crucial. Studies suggest that E209K mutation decreases phosphorylation, increases the survival time of protein, and modifies protein-protein interaction, consequently leading to disruption of calcium flux and lower resistance to apoptosis induction. Unfortunately, to date, only a limited number of research groups have investigated the effects of mutations in the PACS2 gene. Current research on PACS2 syndrome is hampered by the lack of suitable models. While in vitro models using transfected cell lines offer insights, they cannot fully capture the disease's complexity.To address this, utilizing cells from individuals with PACS2 syndrome, specifically induced pluripotent stem cells (iPSCs), holds promise for understanding phenotypic diversity and developing personalized therapies. However, iPSC models may not fully capture tissue-specific effects of the E209K/E211K mutation. In vivo studies using animal models, particularly mice, could overcome these limitations.This review summarizes current knowledge about PACS2 structure and functions, explores the cellular consequences of E209K and E211K mutations, and highlights the potential of iPSC and mouse models in advancing our understanding of PACS2 syndrome.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142910003","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}

{"title":"Climate resilience in goats: a comprehensive review of the genetic basis for adaptation to varied climatic conditions.","authors":"Ram Parsad, Sonika Ahlawat, Meena Bagiyal, Reena Arora, Ritika Gera, Pooja Chhabra, Upasna Sharma, Ajay Singh","doi":"10.1007/s00335-024-10101-z","DOIUrl":"https://doi.org/10.1007/s00335-024-10101-z","url":null,"abstract":"<p><p>The sustainability of livestock systems is widely acknowledged to be threatened by climate change on a worldwide scale. There are worries about the effects this phenomenon may have on the productivity and performance of native livestock species due to its influence on environmental stresses, such as the frequency and severity of unfavorable weather occurrences and the ongoing changes in the agro-ecological landscape. Among the most climatically tolerant livestock animals, goats can survive in a range of environments, from deserts to alpine areas. The domestic goat has undergone significant phenotypic changes in terms of shape, behavior, physiological adaptation, reproduction, and production over their evolutionary journey. It will be possible to better understand the genetic mechanisms underlying successful domestication and the practical breeding strategies leading to the improvement in productivity and resilience to environmental challenges by identifying the genes underlying these modifications. This review explores current knowledge on goat adaptation strategies, emphasizing gene expression patterns, epigenetic modifications, and whole-genome selection signatures. It examines how these molecular mechanisms enable goats to endure heat stress, hypoxia, and other environmental challenges. Furthermore, the review highlights the potential of epigenetic markers and selection signatures in developing climate-resilient goat breeds through marker-assisted selection and genome editing, offering actionable insights into sustainable goat production in the context of global climate change.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909941","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}

{"title":"Comprehensive analysis reveals the prognostic and immunological role of PSMD13 in hepatocellular carcinoma.","authors":"Yun Li, Honghui Liu, Na Liu, Lin Chen, Ruijie Liu","doi":"10.1007/s00335-024-10097-6","DOIUrl":"https://doi.org/10.1007/s00335-024-10097-6","url":null,"abstract":"<p><p>Immune cell infiltration in liver hepatocellular carcinoma (LIHC) is promising for immunotherapy. However, effective predictive markers to accurately predict a tumour's immune status are lacking. PSMD13, a native component of the 26 S proteasome subunit involved in intracellular metabolism, has an unclear association with cancer and immunity. Using bioinformatics analysis of data from the TCGA, we investigated the expression patterns, prognostic values, gene functions, and tumour immune relationships of PSMD13 in LIHC. We developed a prognostic model that incorporates PSMD13 for LIHC and validated the biological functions of PSMD13 in LIHC cells. Furthermore, we analysed the associations between PSMD13 expression and the tumour immune markers CD206 and CD8 in 101 paired liver tissues using immunohistochemistry. PSMD13 was upregulated in LIHC and served as a prognostic biomarker of LIHC. The knockdown of PMSD13 significantly affected the proliferation, migration, and colony formation of LIHC cells. PSMD13 was closely associated with the infiltration of M2 macrophages and the expression of various tumour immune checkpoints. Our study revealed that PSMD13 is a crucial component contributing to the malignant behaviour of LIHC, indicating its essential role in both the prognosis and potential immune microenvironment profile of LIHC.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909959","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}

{"title":"Canine models of inherited retinal diseases: from neglect to well-recognized translational value.","authors":"Valérie L Dufour, Gustavo D Aguirre","doi":"10.1007/s00335-024-10091-y","DOIUrl":"10.1007/s00335-024-10091-y","url":null,"abstract":"<p><p>Large animal models of inherited retinal diseases, particularly dogs, have been extensively used over the past decades to study disease natural history and evaluate therapeutic interventions. Our group of investigators at the University of Pennsylvania, School of Veterinary Medicine, has played a pivotal role in characterizing several of these animal models, documenting the natural history of their diseases, developing gene therapies, and conducting proof-of-concept studies. Additionally, we have assessed the potential toxicity of these therapies for human clinical trials, contributing to the regulatory approval of voretigene neparvovec-rzyl (Luxturna^®) by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of patients with confirmed biallelic mutation-associated retinal dystrophy. In this review, we aim to summarize the clinical features of a subset of these diseases and reflect on the challenges encountered in integrating canine models into the translational pipeline.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909902","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}

{"title":"Identification of EXO1 as a potential biomarker associated with prognosis and tumor immune microenvironment for specific human cancers.","authors":"Jingyun Wang, Fen Liu, Jianfu Heng, Guoli Li","doi":"10.1007/s00335-024-10092-x","DOIUrl":"https://doi.org/10.1007/s00335-024-10092-x","url":null,"abstract":"<p><p>Exonuclease 1 (EXO1) is an evolutionarily conserved exonuclease, which have function on maintaining genomic stability. Elevated expression of EXO1 has been reported in certain cancers. However, a comprehensive pan-cancer analysis of EXO1 is still lacking and its role in human cancer development remains poorly understood. This study aims to investigate the genetic alterations and expression perturbations of EXO1 and evaluate its potential clinical relevance in different cancer types. By employing powerful bioinformatics tools and utilizing data sourced from The Cancer Genome Atlas and the Genotype-Tissue Expression datasets, a comprehensive pan-cancer analysis of EXO1 was conducted, including an examination of gene expression, alterations in genetics, DNA methylation patterns, survival outcomes, clinical traits, immune features, and functional enrichment analysis. EXO1 was found to be highly expressed across 20 tumor types, including lung adenocarcinoma, lung squamous cell carcinoma, and breast invasive carcinoma. The expression levels of EXO1 are frequently associated with later clinical stages and unfavorable outcomes. Genetic alterations in EXO1 were predominantly found to be amplified in a pan-cancer context. A total of 131 missense mutations, 24 truncation mutations, 1 in-frame mutation, 6 splice site mutations, and 1 fusion mutation were identified. Interestingly, a significant co-occurrence of alterations in EXO1 with other ten gene alterations were identified. The expression of EXO1 in multiple tumors showed a significant correlation with tumor mutational burden, microsatellite instability, and genes related to immunological checkpoints. In most types of cancer, a strong correlation exists between the expression of EXO1 and the infiltration of CD4⁺ Th2 cells, memory CD4⁺ T cells, myeloid-derived suppressor cells, and common lymphoid progenitors. Analysis of 150 genes related to EXO1 demonstrate an enrichment in processes such as cell cycle regulation, DNA damage repair, and relevant signaling pathways, suggesting a possible mechanism through which EXO1 may facilitate tumor development. This study offers a deep insight into the role of EXO1 in different types of human cancers, indicating that EXO1 could act as an important prognostic biomarker and a therapeutic target for certain types of cancer.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882468","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}

{"title":"From gut to kidney: microbiota modulates stone risk through inflammation-a mediated Mendelian randomization study.","authors":"Long Guo, Qing Lan, Min Zhou, Fei Liu","doi":"10.1007/s00335-024-10094-9","DOIUrl":"https://doi.org/10.1007/s00335-024-10094-9","url":null,"abstract":"<p><p>The gut microbiota (GM) can affect the immune system, which can lead to a variety of diseases, as confirmed by many studies. However, the exact mechanism by which GM affects kidney stone incidence through the immune system remains unclear. This study used a two-step, two-sample Mendelian randomization (MR) analysis by inverse variance weighting (IVW) method as well as Bayesian weighting (BWMR) to find out how the gut microbiota and inflammatory cytokines contribute to kidney stones, followed by a mediated MR analysis to exploreHow inflammatory cytokines are involved in the connection with the gut microbiota and kidney stones. MR analysis revealed that seven intestinal flora were protective against kidney stones, including family. Actinomycetaceae, family.Clostridiaceae1, genus.Clostridiumsensustricto1, genus. Hungatella, genus.LachnospiraceaeUCG001, genus.LachnospiraceaeUCG008 and order. Actinomycetales, while four intestinal flora, including genus. Haemophilus, genus. RuminococcaceaeUCG010, order.Rhodospirillales and phylum.Actinobacteria may increase the risk of kidney stones. In addition, it was confirmed that seven Inflammatory cytokines DNER, IL-18, IL-1α, SLAMF1, STAMPB, CST5 and FGF-5 in association with kidney stones. Notably, the mediating MR indicated the causal effect of phylum. Actinobacteria and order. Rhodospirillales gut group on kidney stones was mainly modulated by IL-18 levels, with mediating effects accounting for 15.8% and 12.8% of the total effect, respectively. The present study demonstrates this phylum. Actinobacteria and order. Rhodospirillales flora have an important role in reducing the risk of kidney stones and act mainly by modulating IL-18 levels.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882462","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}

{"title":"Protein family FAM241 in human and mouse.","authors":"Quinlan Doctrove, Young Park, Daniel G Calame, Jacob Kitzman, Guy M Lenk, Miriam H Meisler","doi":"10.1007/s00335-024-10096-7","DOIUrl":"https://doi.org/10.1007/s00335-024-10096-7","url":null,"abstract":"<p><p>FAM241B was isolated in a genome-wide inactivation screen for generation of enlarged lysosomes. FAM241B and FAM241A comprise protein family FAM241 encoding proteins of 121 and 132 amino acid residues, respectively. The proteins exhibit 25% amino acid sequence identity and contain a domain of unknown function (DUF4605; pfam15378) that is conserved from primitive multicellular eukaryotes through vertebrates. Phylogenetic comparison indicates that duplication of the ancestral FAM241B gene occurred prior to the origin of fish. FAM241B has been deleted from the avian lineage. Fam241a and Fam241b are widely expressed in mouse tissues. Experimental knockout of mouse Fam241a, Fam241b, and the double knockout, did not generate a visible phenotype. Knockout of Fam241A and Fam241B did not exacerbate the phenotype of FIG4 null mice. RNAseq of brain RNA from double knockout mice detected reduced expression of several genes including Arke1e1 and RnaseL. The human variant p.Val115Gly in FAM241B was identified in a patient with developmental delay. Lysosome morphology in patient-derived fibroblasts was normal. In previous studies, FAM241A and FAM241B appeared to co-localize with proteins of the endoplasmic reticulum. The molecular function of this ancient protein family remains to be determined.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882471","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}

{"title":"The effect of different approaches to determining the regularization parameter of bayesian LASSO on the accuracy of genomic prediction.","authors":"Hamid Sahebalam, Mohsen Gholizadeh, Seyed Hassan Hafezian","doi":"10.1007/s00335-024-10088-7","DOIUrl":"https://doi.org/10.1007/s00335-024-10088-7","url":null,"abstract":"<p><p>Using dense genomic markers opens up new opportunities and challenges for breeding programs. The need to penalize marker-specific regression coefficients becomes particularly important when dense markers are available. Therefore, fitting the marker effects to observations using a regularization technique, such as Bayesian LASSO (BL) regression, is of great interesting. When the Laplace prior distribution is applied to the regression coefficients, BL can be interpreted as a regularization of the <math><mrow><mspace></mspace> <mi>L</mi> <mn>1</mn></mrow> </math> norm based on the Bayesian approach. A critical issue is the appropriate selection of hyperparameters values in the prior distributions of regularization techniques, as these values essentially control the sparsity in the estimated model. The purpose of this study was to evaluate different approaches for selecting the regularization parameter in BL, based on fully Bayesian approaches-such as gamma prior (BL_Gamma), beta prior (BL_Beta) and fixed prior (BL_Fixed) as well as data-driven approaches like cross-validation based on mean square error (BL_CV_MSE) and prediction accuracy (BL_CV_PA). Additionally, information-criteria-based methods including Akaike's information criterion (BL_AIC), Bayesian information criterion (BL_BIC) and Deviance information criterion (BL_DIC), were explored. For this purpose, a genome containing eight chromosomes (each 1 Morgan in length) with 100 randomly distributed quantitative trait loci was simulated. The studied scenarios were as follows: Scenario 1 involved 4000 markers and heritability of 0.2, scenario 2 involved 4000 markers and heritability of 0.6, scenario 3 involved 16,000 markers and heritability of 0.2; and scenario 4 involved 16,000 markers and heritability of 0.6. The results showed that among the fully Bayesian and cross-validation approaches, BL_Gamma, BL_Beta, and BL_CV_MSE provided the highest prediction accuracy (PA) in scenario 1 and 3. With increased marker density and heritability (scenario 4), the cross-validation approaches performed slightly better. The information-criteria-based methods demonstrated the lowest PA. Increasing heritability and marker density led to a decrease and an increase in the model penalty on the regression coefficients, respectively. The PA obtained in the target population ranged from 0.210 to 0.413 in Scenario 1, 0.402 to 0.600 in Scenario 2, 0.256 to 0.442 in Scenario 3, and 0.478 to 0.653 in Scenario 4. In generally, fully Bayesian approaches based on random priors for the regularization parameter are recommended for BL, as they provide acceptable PA with lower computational loads.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807598","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}

{"title":"Biological mechanism and functional verification of key genes related to major depressive disorder and type 2 diabetes mellitus.","authors":"Tao Fang, Na Shen, Zhemin Shi, Weishun Luo, Yanbo Di, Xuan Liu, Shengnan Ma, Jing Wang, Shike Hou","doi":"10.1007/s00335-024-10090-z","DOIUrl":"https://doi.org/10.1007/s00335-024-10090-z","url":null,"abstract":"<p><p>Major depressive disorder (MDD) and type 2 diabetes (T₂D) have been shown to be linked, but a comprehensive understanding of the underlying molecular mechanisms remains elusive. The purpose of this study was to explore the biological relationship between MDD and T₂D and verify the functional roles of key genes. We used the Gene Expression Omnibus database to investigate the targets associated with MDD and T₂D. Using linear models for microarray data, differentially expressed genes associated with MDD and T₂D were identified in GSE76826 and GSE95849, respectively, and 126 shared genes were significantly upregulated. Weighted gene coexpression network analysis identified modules associated with MDD and T₂D in the GSE38206 and GSE20966 datasets and identified 8 common genes. Functional enrichment analysis revealed that these genes were enriched in cell signaling, enzyme activity, cell structure and amino acid biosynthesis and involved in cell death pathways. Finally, combined with the CTD and GeneCards databases, lysophosphatidylglycerol acyltransferase 1 (LPGAT1) was identified as a key gene. LPGAT1 was validated in GSE201332 and GSE182117, and the subject operating characteristic curve showed good diagnostic potential for MDD and T₂D. Additionally, we used an in vitro model of MDD related to T₂D to verify the expression of LPGAT1. A subsequent gene knockdown assay revealed that the downregulation of LPGAT1 improved mitochondrial function and reduced apoptosis in damaged neurons. Taken together, our results highlight the role of LPGAT1 in the connection between MDD and T₂D, and these findings provide new insights into potential therapeutic targets for depression associated with diabetes.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801471","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}