Mammalian Genome最新文献

{"title":"Elucidation of population stratifying markers and selective sweeps in crossbred Landlly pig population using genome-wide SNP data.","authors":"Tapendra Saini, Anuj Chauhan, Sheikh Firdous Ahmad, Amit Kumar, Sakshi Vaishnav, Shivani Singh, Arnav Mehrotra, Bharat Bhushan, G K Gaur, Triveni Dutt","doi":"10.1007/s00335-024-10029-4","DOIUrl":"10.1007/s00335-024-10029-4","url":null,"abstract":"<p><p>The present study was aimed at the identification of population stratifying markers from the commercial porcine SNP 60K array and elucidate the genome-wide selective sweeps in the crossbred Landlly pig population. Original genotyping data, generated on Landlly pigs, was merged in various combinations with global suid breeds that were grouped as exotic (global pig breeds excluding Indian and Chinese), Chinese (Chinese pig breeds only), and outgroup pig populations. Post quality control, the genome-wide SNPs were ranked for their stratifying power within each dataset in TRES (using three different criteria) and FIFS programs and top-ranked SNPs (0.5K, 1K, 2K, 3K, and 4K densities) were selected. PCA plots were used to assess the stratification power of low-density panels. Selective sweeps were elucidated in the Landlly population using intra- and inter-population haplotype statistics. Additionally, Tajima's D-statistics were calculated to determine the status of balancing selection in the Landlly population. PCA plots showed 0.5K marker density to effectively stratify Landlly from other pig populations. The A-score in DAPC program revealed the Delta statistic of marker selection to outperform other methods (informativeness and F_ST methods) and that 3000-marker density was suitable for stratification of Landlly animals from exotic pig populations. The results from selective sweep analysis revealed the Landlly population to be under selection for mammary (NAV2), reproductive efficiency (JMY, SERGEF, and MAP3K20), body conformation (FHIT, WNT2, ASRB, DMGDH, and BHMT), feed efficiency (CSRNP1 and ADRA1A), and immunity (U6, MYO3B, RBMS3, and FAM78B) traits. More than two methods suggested sweeps for immunity and feed efficiency traits, thus giving a strong indication for selection in this direction. The study is the first of its kind in Indian pig breeds with a comparison against global breeds. In conclusion, 500 markers were able to effectively stratify the breeds. Different traits under selective sweeps (natural or artificial selection) can be exploited for further improvement.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"170-185"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140131858","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":"Construction of a pathological model of skin lesions in acute herpes zoster virus infection and its molecular mechanism","authors":"Hao Zhou, Zheng Ye, Zhao Gao, Chengxi Xi, Jinxia Yin, Yanjun Sun, Bo Sun","doi":"10.1007/s00335-024-10039-2","DOIUrl":"https://doi.org/10.1007/s00335-024-10039-2","url":null,"abstract":"<p>Varicella-zoster virus (VZV), a common pathogen with humans as the sole host, causes primary infection and undergoes a latent period in sensory ganglia. The recurrence of VZV is often accompanied by severe neuralgia in skin tissue, which has a serious impact on the life of patients. During the acute infection of VZV, there are few related studies on the pathophysiological mechanism of skin tissue. In this study, transcriptome sequencing data from the acute response period within 2 days of VZV antigen stimulation of the skin were used to explore a model of the trajectory of skin tissue changes during VZV infection. It was found that early VZV antigen stimulation caused activation of mainly natural immune-related signaling pathways, while in the late phase activation of mainly active immune-related signaling pathways. JAK-STAT, NFκB, and TNFα signaling pathways are gradually activated with the progression of infection, while Hypoxia is progressively inhibited. In addition, we found that dendritic cell-mediated immune responses play a dominant role in the lesion damage caused by VZV antigen stimulation of the skin. This study provides a theoretical basis for the study of the molecular mechanisms of skin lesions during acute VZV infection.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"50 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140593496","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":"Exploring key genes and pathways associated with sex differences in autism spectrum disorder: integrated bioinformatic analysis","authors":"Himani Nautiyal, Akanksha Jaiswar, Prabhash Kumar Jha, Shubham Dwivedi","doi":"10.1007/s00335-024-10036-5","DOIUrl":"https://doi.org/10.1007/s00335-024-10036-5","url":null,"abstract":"<p>Autism spectrum disorder (ASD) is a heterogenous neurodevelopmental disorder marked by functional abnormalities in brain that causes social and linguistic difficulties. The incidence of ASD is more prevalent in males compared to females, but the underlying mechanism, as well as molecular indications for identifying sex-specific differences in ASD symptoms remain unknown. Thus, impacting the development of personalized strategy towards pharmacotherapy of ASD. The current study employs an integrated bioinformatic approach to investigate the genes and pathways uniquely associated with sex specific differences in autistic individuals. Based on microarray dataset (GSE6575) extracted from the gene expression omnibus, the dysregulated genes between the autistic and the neurotypical individuals for both sexes were identified. Gene set enrichment analysis was performed to ascertain biological activities linked to the dysregulated genes. Protein–protein interaction network analysis was carried out to identify hub genes. The identified hub genes were examined to determine their functions and involvement in the associated pathways using Enrichr. Additionally, hub genes were validated from autism-associated databases and the potential small molecules targeting the hub genes were identified. The present study utilized whole blood transcriptomic gene expression analysis data and identified 2211 and 958 differentially expressed unique genes in males and females respectively. The functional enrichment analysis revealed that male hub genes were functionally associated with RNA polymerase II mediated transcriptional regulation whereas female hub genes were involved in intracellular signal transduction and cell migration. The top male hub genes exhibited functional enrichment in tyrosine kinase signalling pathway. The pathway enrichment analysis of male hub genes indicates the enrichment of papillomavirus infection. Female hub genes were enriched in androgen receptor signalling pathway and functionally enriched in focal adhesion specific excision repair. Identified drug like candidates targeting these genes may serve as a potential sex specific therapeutics. Wortmannin for males, 5-Fluorouracil for females had the highest scores. Targeted and sex-specific pharmacotherapies may be created for the management of ASD. The current investigation identifies sex-specific molecular signatures derived from whole blood which may serve as a potential peripheral sex-specific biomarkers for ASD. The study also uncovers the possible pharmacological interventions against the selected genes/pathway, providing support in development of therapeutic strategies to mitigate ASD. However, experimental proofs on biological systems are warranted.</p><h3 data-test=\"abstract-sub-heading\">Graphical abstract</h3>\u0000","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"650 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140593495","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":"Molecular insights into Pashmina fiber production: comparative skin transcriptomic analysis of Changthangi goats and sheep","authors":"Sonika Ahlawat, Mahanthi Vasu, M.A. Mir, Manoj Kumar Singh, Reena Arora, Rekha Sharma, Pooja Chhabra, Upasna Sharma","doi":"10.1007/s00335-024-10040-9","DOIUrl":"https://doi.org/10.1007/s00335-024-10040-9","url":null,"abstract":"<p>Ladakh, one of the highest inhabited regions globally, hosts the unique Changthangi goat, renowned for producing Pashmina, the world’s most luxurious natural fiber. In comparison, the fiber derived from Changthangi sheep is considered next only to Pashmina. This research endeavors to compare the skin transcriptome profiles of Changthangi goats and Changthangi sheep, aiming to discern the molecular determinants behind the recognition of Changthangi goats as the source of Pashmina. Drawing upon previously conducted studies, a collective of 225 genes correlated with fiber characteristics were extracted from the differentially expressed genes noticed between the two species (p-value of ≤ 0.05 and a log₂ fold change of ≥ 1.5). These genes were analyzed using DAVID software to understand their biological functions and to identify enriched KEGG and Reactome pathways. The protein-protein interaction networks were constructed using Cytoscape, cytoHubba, and STRING to focus on key genes and infer their biological significance. Comparative transcriptome analysis revealed significantly higher expression of genes involved in signaling pathways like Wnt, MAPK, PI3K-Akt, Hedgehog, associated with fiber development and quality in Changthangi goats. These pathways play crucial roles in hair follicle (HF) formation, maintenance of epidermal stem cells, and fiber characteristics. Findings also highlight the enrichment of cell adhesion molecules and ECM-receptor interaction, emphasizing their roles in HF structure, growth, and signaling. This investigation offers an in-depth understanding of the molecular intricacies governing Pashmina production in Changthangi goats, providing valuable insights into their unique genetic makeup and underlying mechanisms influencing the exceptional quality of Pashmina fibers.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"10 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140593493","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":"CDC167 exhibits potential as a biomarker for airway inflammation in asthma","authors":"Yukai Zhong, Qiong Wu, Li Cai, Yuanjing Chen, Qi Shen","doi":"10.1007/s00335-024-10037-4","DOIUrl":"https://doi.org/10.1007/s00335-024-10037-4","url":null,"abstract":"<p>Current asthma treatments have been discovered to decrease the risk of disease progression. Herein, we aimed to characterize novel potential therapeutic targets for asthma. Differentially expressed genes (DEGs) for GSE64913 and GSE137268 datasets were characterized. Weighted correlation network analysis (WGCNA) was used to identify trait-related module genes within the GSE67472 dataset. The intersection of the module genes of interest, as well as the DEGs, comprised the key module genes that underwent additional candidate gene screening using machine learning. In addition, a bioinformatics-based approach was used to analyze the relative expression levels, diagnostic values, and reverently enriched pathways of the screened candidate genes. Furthermore, the candidate genes were silenced in asthmatic mice, and the inflammation and lung injury in the mice were validated. A total of 1710 DEGs were characterized in GSE64913 and GSE137268 for asthma patients. WGCNA identified 2367 asthma module genes, of which 285 overlapped with 1710 DEGs. Four candidate genes, CDC167, POSTN, SEC14L1, and SERPINB2, were validated using the intersection genes of three machine learning algorithms, including Least Absolute Shrinkage and Selection Operator, Random Forest, and Support Vector Machine. All the candidate genes were significantly upregulated in asthma patients and demonstrated diagnostic utility for asthma. Furthermore, silencing CDC167 reduced the levels of inflammatory cytokines significantly and alleviated lung injury in ovalbumin (OVA)-induced asthmatic mice. Our study demonstrated that CDC167 exhibits potential as diagnostic markers and therapeutic targets for asthma patients.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"207 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140593499","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 genetic variants affecting reproduction traits in Vrindavani cattle.","authors":"Munish Gangwar, Subodh Kumar, Sheikh Firdous Ahmad, Akansha Singh, Swati Agrawal, P L Anitta, Amit Kumar","doi":"10.1007/s00335-023-10023-2","DOIUrl":"10.1007/s00335-023-10023-2","url":null,"abstract":"<p><p>Genome-wide association studies (GWAS) are one of the best ways to look into the connection between single-nucleotide polymorphisms (SNPs) and the phenotypic performance. This study aimed to identify the genetic variants that significantly affect the important reproduction traits in Vrindavani cattle using genome-wide SNP chip array data. In this study, 96 randomly chosen Vrindavani cows were genotyped using the Illumina Bovine50K BeadChip platform. A linear regression model of the genome-wide association study was fitted in the PLINK program between genome-wide SNP markers and reproduction traits, including age at first calving (AFC), inter-calving period (ICP), dry days (DD), and service period (SP) across the first three lactations. Information on different QTLs and genes, overlapping or adjacent to genomic coordinates of significant SNPs, was also mined from relevant databases in order to identify the biological pathways associated with reproductive traits in bovine. The Bonferroni correction resulted in total 39 SNP markers present on different chromosomes being identified that significantly affected the variation in AFC (6 SNPs), ICP (7 SNPs), DD (9 SNPs), and SP (17 SNPs). Novel potential candidate genes associated with reproductive traits that were identified using the GWAS methodology included UMPS, ITGB5, ADAM2, UPK1B, TEX55, bta-mir-708, TMPO, TDRD5, MAPRE2, PTER, AP3B1, DPP8, PLAT, TXN2, NDUFAF1, TGFA, DTNA, RSU1, KCNQ1, ADAM32, and CHST8. The significant SNPs and genes associated with the reproductive traits and the enriched genes may be exploited as candidate biomarkers in animal improvement programs, especially for improved reproduction performance in bovines.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"99-111"},"PeriodicalIF":2.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71483288","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":"E3 ubiquitin ligase COP1-mediated CEBPB ubiquitination regulates the inflammatory response of macrophages in sepsis-induced myocardial injury.","authors":"Yangzi Yu, Qiang Fu, Jiarui Li, Xianming Zen, Jing Li","doi":"10.1007/s00335-023-10027-y","DOIUrl":"10.1007/s00335-023-10027-y","url":null,"abstract":"<p><p>CCAAT/enhancer-binding protein beta (CEBPB) has been associated with sepsis. However, its role in sepsis-induced myocardial injury (SIMI) remains ill-defined. This research was designed to illustrate the involvement of CEBPB in SIMI and its upstream modifier. The transcriptomic changes in heart biopsies of mice that had undergone polymicrobial sepsis were downloaded from the GEO dataset for KEGG enrichment analysis. CEBPB, on the TNF signaling pathway, was significantly enhanced in the myocardial tissues of mice with SIMI. Downregulation of CEBPB alleviated SIMI, as evidenced by minor myocardial injury and inflammatory manifestations. Moreover, ubiquitination modification of CEBPB by constitutive photomorphogenesis protein 1 homolog (COP1) led to the degradation of CEBPB and inhibited inflammatory responses in macrophages. Upregulation of COP1 protected against SIMI in mice overexpressing CEBPB. Collectively, our findings demonstrated that COP1 protected the heart against SIMI through the ubiquitination modification of CEBPB, which might be a novel therapeutic approach in the future.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"56-67"},"PeriodicalIF":2.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138047315","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":"Cytosolic nucleic acid sensing and mitochondrial transcriptomic changes as early triggers of metabolic disease in db/db mice.","authors":"Agnieszka H Ludwig-Słomczyńska, Michał T Seweryn, Jerzy Wiater, Agnieszka Borys, Anna Ledwoń, Magdalena Druszczyńska, Magdalena Łabieniec-Watała, Grzegorz J Lis, Paweł P Wołkow","doi":"10.1007/s00335-023-10026-z","DOIUrl":"10.1007/s00335-023-10026-z","url":null,"abstract":"<p><p>Animal models of diabetes, such as db/db mice, are a useful tool for deciphering the genetic background of molecular changes at the initial stages of disease development. Our goal was to find early transcriptomic changes in three tissues involved in metabolism regulation in db/db mice: adipose tissue, muscle tissue and liver tissue. Nine animals (three per time point) were studied. Tissues were collected at 8, 12 and 16 weeks of age. Transcriptome-wide analysis was performed using mRNA-seq. Libraries were sequenced on NextSeq (Illumina). Differential expression (DE) analysis was performed with edgeR. The analysis of the gene expression profile shared by all three tissues revealed eight upregulated genes (Irf7, Sp100, Neb, Stat2, Oas2, Rtp4, H2-T24 and Oasl2) as early as between 8 and 12 weeks of age. The most pronounced differences were found in liver tissue: nine DE genes between 8 and 12 weeks of age (Irf7, Ly6a, Ly6g6d, H2-Dma, Pld4, Ly86, Fcer1g, Ly6e and Idi1) and five between 12 and 16 weeks of age (Irf7, Plac8, Ifi44, Xaf1 and Ly6a) (adj. p-value < 0.05). The mitochondrial transcriptomic profile also changed with time: we found two downregulated genes in mice between 8 and 12 weeks old (Ckmt2 and Cox6a2) and five DE genes between 12 and 16 weeks of age (Mavs, Tomm40L, Mtfp1, Ckmt2 and Cox6a2). The KEGG pathway analysis showed significant enrichment in pathways related to the autoimmune response and cytosolic DNA sensing. Our results suggest an important involvement of the immunological response, mainly cytosolic nucleic acid sensing, and mitochondrial signalling in the early stages of diabetes and obesity.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"68-76"},"PeriodicalIF":2.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10884043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136398010","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}

{"title":"Mitral valve transcriptome analysis in thirty-four age-matched Cavalier King Charles Spaniels with or without congestive heart failure caused by myxomatous mitral valve disease.","authors":"Maria J Reimann, Signe Cremer, Liselotte Christiansen, Emil Ibragimov, Fei Gao, Susanna Cirera, Merete Fredholm, Lisbeth H Olsen, Peter Karlskov-Mortensen","doi":"10.1007/s00335-023-10024-1","DOIUrl":"10.1007/s00335-023-10024-1","url":null,"abstract":"<p><p>We here report the results of a mitral valve transcriptome study designed to identify genes and molecular pathways involved in development of congestive heart failure (CHF) following myxomatous mitral valve disease (MMVD) in dogs. The study is focused on a cohort of elderly age-matched dogs (n = 34, age ~ 10 years) from a single breed-Cavalier King Charles Spaniels (CKCS)-with a high incidence of MMVD. The cohort comprises 19 dogs (10♀, 9♂) without MMVD-associated CHF, and 15 dogs (6♀, 9♂) with CHF caused by MMVD; i.e., we compare gene expression in breed and age-matched groups of dogs, which only differ with respect to CHF status. We identify 56 genes, which are differentially expressed between the two groups. In this list of genes, we confirm an enrichment of genes related to the TNFβ-signaling pathway, extracellular matrix organization, vascular development, and endothelium damage, which also have been identified in previous studies. However, the genes with the greatest difference in expression between the two groups are CNTN3 and MYH1. Both genes encode proteins, which are predicted to have an effect on the contractile activity of myocardial cells, which in turn may have an effect on valvular performance and hemodynamics across the mitral valve. This may result in shear forces with impact on MMVD progression.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"77-89"},"PeriodicalIF":2.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10884180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71483289","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}

{"title":"Mapping novel QTL and fine mapping of previously identified QTL associated with glucose tolerance using the collaborative cross mice.","authors":"Hanifa J Abu-Toamih-Atamni, Iqbal M Lone, Ilona Binenbaum, Richard Mott, Eleftherios Pilalis, Aristotelis Chatziioannou, Fuad A Iraqi","doi":"10.1007/s00335-023-10025-0","DOIUrl":"10.1007/s00335-023-10025-0","url":null,"abstract":"<p><p>A chronic metabolic illness, type 2 diabetes (T2D) is a polygenic and multifactorial complicated disease. With an estimated 463 million persons aged 20 to 79 having diabetes, the number is expected to rise to 700 million by 2045, creating a significant worldwide health burden. Polygenic variants of diabetes are influenced by environmental variables. T2D is regarded as a silent illness that can advance for years before being diagnosed. Finding genetic markers for T2D and metabolic syndrome in groups with similar environmental exposure is therefore essential to understanding the mechanism of such complex characteristic illnesses. So herein, we demonstrated the exclusive use of the collaborative cross (CC) mouse reference population to identify novel quantitative trait loci (QTL) and, subsequently, suggested genes associated with host glucose tolerance in response to a high-fat diet. In this study, we used 539 mice from 60 different CC lines. The diabetogenic effect in response to high-fat dietary challenge was measured by the three-hour intraperitoneal glucose tolerance test (IPGTT) test after 12 weeks of dietary challenge. Data analysis was performed using a statistical software package IBM SPSS Statistic 23. Afterward, blood glucose concentration at the specific and between different time points during the IPGTT assay and the total area under the curve (AUC0-180) of the glucose clearance was computed and utilized as a marker for the presence and severity of diabetes. The observed AUC0-180 averages for males and females were 51,267.5 and 36,537.5 mg/dL, respectively, representing a 1.4-fold difference in favor of females with lower AUC0-180 indicating adequate glucose clearance. The AUC0-180 mean differences between the sexes within each specific CC line varied widely within the CC population. A total of 46 QTL associated with the different studied phenotypes, designated as T2DSL and its number, for Type 2 Diabetes Specific Locus and its number, were identified during our study, among which 19 QTL were not previously mapped. The genomic interval of the remaining 27 QTL previously reported, were fine mapped in our study. The genomic positions of 40 of the mapped QTL overlapped (clustered) on 11 different peaks or close genomic positions, while the remaining 6 QTL were unique. Further, our study showed a complex pattern of haplotype effects of the founders, with the wild-derived strains (mainly PWK) playing a significant role in the increase of AUC values.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"31-55"},"PeriodicalIF":2.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136398011","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}