BMC Genomics最新文献

{"title":"Genomic alterations of marine yeast Scheffersomyces spartinae under spontaneous and mutagenic conditions.","authors":"Yu-Ting Bai, Awkash Sharma, Qian Xiang, Li-Yan Tian, Ke-Jing Li, Bao-Ying Guo, Lei Qi, Dao-Qiong Zheng","doi":"10.1186/s12864-025-11479-z","DOIUrl":"10.1186/s12864-025-11479-z","url":null,"abstract":"<p><strong>Background: </strong>Understanding the mechanisms of genetic evolution in marine yeasts is essential for their ecological and biotechnological applications. Scheffersomyces spartinae, an ascomycetous yeast species, characterized by its remarkable robustness and carbon source utilization capability, has garnered significant attention for its biotechnological potential.</p><p><strong>Results: </strong>In this study, we investigated the spontaneous and induced genomic alterations of the marine yeast S. spartinae under various conditions. Through mutation accumulation experiments combined with whole-genome sequencing, we revealed that the rates of spontaneous single nucleotide variations and small insertions and deletions were 6.3 × 10⁻¹¹ and 1.4 × 10⁻¹¹ per base pair per cell division, respectively, in S. spartinae. The predominant type of base substitution was C-to-T or G-to-A, likely induced by cytosine deamination. Template slippage during DNA replication emerged as the primary cause of small InDels. 50 J/m² UV treatment elevated the SNV rate by 124-fold, with C-to-T substitutions occurring at the 5'-TC-3' motif and T-to-C substitutions at the 5'-TT-3' motif being the most prominent features. Exposure to 50 µg/mL Zeocin resulted in 76-fold and 71-fold increases in the rates of SNVs and InDels, respectively, with frequent T-to-A mutations and T deletions occurring at the 5'-GT-3' motifs. Heat stress at 37 °C increased the SNVs and InDels rates to 1.4 × 10⁻¹⁰ and 7.5 × 10⁻¹¹ per base pair per cell division. Notably, this study demonstrated that large deletions and duplications (> 1 kb) and aneuploidies are less likely to occur in S. spartinae compared to other yeast species, suggesting that this organism is less tolerant to large-scale genomic alterations. In contrast, we observed a marked decrease in rDNA copy numbers when S. spartinae cells were cultivated at elevated temperature conditions. This finding indicates that variations in rDNA copy numbers might act as an adaptive strategy for yeasts in response to fluctuating temperatures.</p><p><strong>Conclusions: </strong>Our findings provide novel insights into the patterns and genetic mechanisms underlying genomic evolution in yeasts.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"297"},"PeriodicalIF":3.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Performance evaluation of structural variation detection using DNBSEQ whole-genome sequencing.","authors":"Junhua Rao, Huijuan Luo, Dan An, Xinming Liang, Lihua Peng, Fang Chen","doi":"10.1186/s12864-025-11494-0","DOIUrl":"10.1186/s12864-025-11494-0","url":null,"abstract":"<p><strong>Background: </strong>DNBSEQ platforms have been widely used for variation detection, including single-nucleotide variants (SNVs) and short insertions and deletions (INDELs), which is comparable to Illumina. However, the performance and even characteristics of structural variations (SVs) detection using DNBSEQ platforms are still unclear.</p><p><strong>Results: </strong>In this study, we assessed the detection of SVs using 40 tools on eight DNBSEQ whole-genome sequencing (WGS) datasets and two Illumina WGS datasets of NA12878. Our findings confirmed that the performance of SVs detection using the same tool on DNBSEQ and Illumina datasets was highly consistent, with correlations greater than 0.80 on metrics of number, size, precision and sensitivity, respectively. Furthermore, we constructed a \"DNBSEQ\" SV set (4,785 SVs) from the DNBSEQ datasets and an \"Illumina\" SV set (6,797 SVs) from the Illumina datasets. We found that these two SV sets were highly consistent of SV sites and genomic characteristics, including repetitive regions, GC distribution, difficult-to-sequence regions, and gene features, indicating the robustness of our comparative analysis and highlights the value of both platforms in understanding the genomic context of SVs.</p><p><strong>Conclusions: </strong>Our study systematically analyzed and characterized germline SVs detected on WGS datasets sequenced from DNBSEQ platforms, providing a benchmark resource for further studies of SVs using DNBSEQ platforms.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"299"},"PeriodicalIF":3.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic revelation and meditation on the significance of long exons using representative eukaryotic genomes.","authors":"Yuange Duan, Qi Cao","doi":"10.1186/s12864-025-11504-1","DOIUrl":"10.1186/s12864-025-11504-1","url":null,"abstract":"<p><strong>Background: </strong>Long exons/introns are not evenly distributed in the genome, but the biological significance of this phenomenon remains elusive.</p><p><strong>Materials and methods: </strong>Exon properties were analyzed in seven well-annotated reference genomes, including human and other representative model organisms: mouse, fruitfly, worm, mouse-ear cress, corn, and rice.</p><p><strong>Results: </strong>In all species, last exons in genes tend to be the longest. Additionally, we found that (1) canonical splicing motifs are strongly underrepresented in 3'UTR; (2) Last exons tend to have low GC content; (3) Comparing with other species, first exons in D. melanogaster genes demonstrate lower GC content than internal exons.</p><p><strong>Conclusions: </strong>It cannot be excluded that last exons of genes exert essential regulatory roles and is subjected to natural selection, exhibiting differential splicing tendency, and GC content compared to other parts of the gene body.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"290"},"PeriodicalIF":3.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Epidermal growth factor dampens pro-inflammatory gene expression induced by interferon-gamma in global transcriptome analysis of keratinocytes.","authors":"David C Gibbs, Myles R McCrary, Carlos S Moreno, Lindsey Seldin, Chaoran Li, Nourine A H Kamili, Brian P Pollack","doi":"10.1186/s12864-025-11457-5","DOIUrl":"10.1186/s12864-025-11457-5","url":null,"abstract":"","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"291"},"PeriodicalIF":3.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic-transcriptomic analysis identifies the Syrian hamster as a superior animal model for human diseases.","authors":"Chuchu Wang, Zhenguo Cheng, Jinxin Miao, Xia Xue, Yunshu Dong, Li Zhao, Haoran Guo, Jianyao Wang, Zhizhong Wang, Shuangshuang Lu, Guangming Fang, Ying Peng, Yafei Zhai, Zhongxian Zhang, Dongling Gao, Zhimin Wang, Pengju Wang, Lirong Zhang, Louisa S Chard Dunmall, Jun Wang, Wenxue Tang, Xiaowei Li, Zhongren Ding, Xiaoyan Zhao, Ling Li, Nicholas R Lemoine, Zhongde Wang, Daniel Tonge, Wenjie Tan, Jianzeng Dong, Yaohe Wang","doi":"10.1186/s12864-025-11393-4","DOIUrl":"10.1186/s12864-025-11393-4","url":null,"abstract":"<p><strong>Background: </strong>The Syrian hamster (Mesocricetus auratus) has shown promise as a human diseases model, recapitulating features of different human diseases including COVID-19. However, the landscape of its genome and transcriptome has not been systematically dissected, restricting its potential applications.</p><p><strong>Results: </strong>Here we provide a complete analysis of the genome and transcriptome of the Syrian hamster and found that its lineage diverged from that of the Chinese hamster (Cricetulus griseus) around 29.4 million years ago. 21,387 protein-coding genes were identified, with 90.03% of the 2.56G base pair sequence being anchored to 22 chromosomes. Further comparison of the transcriptomes from 15 tissues of the Syrian hamster revealed that the Syrian hamster shares a pattern of alternative splicing modes more similar to humans, compared to rats and mice. An integrated genomic-transcriptomic analysis revealed that the Syrian hamster also has genetic and biological advantages as a superior animal model for cardiovascular diseases. Strikingly, several genes involved in SARS-COV-2 infection, including ACE2, present a higher homology with humans compared to other rodents and show the same function as their human counterparts.</p><p><strong>Conclusion: </strong>The detailed molecular characterisation of the Syrian hamster in the present study opens a wealth of fundamental resources from this small rodent for future research into human disease pathology and treatment.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"286"},"PeriodicalIF":3.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying cross-tissue molecular targets of lung function by multi-omics integration analysis from DNA methylation and gene expression of diverse human tissues.","authors":"Shisheng Peng, Jinlong Fang, Weiliang Mo, Guodong Hu, Senquan Wu","doi":"10.1186/s12864-025-11476-2","DOIUrl":"10.1186/s12864-025-11476-2","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have reported several genetic loci associated with lung function. However, the mediating mechanism between these genetic loci and lung function phenotype is rarely explored. In this research, we used a cross-tissue multi-omics post-GWAS analysis to explain the associations between DNA methylation, gene expression, and lung function.</p><p><strong>Methods: </strong>We conducted integration analyses of lung function traits using genome-wide association study (GWAS) summary data alongside expression quantitative trait loci (eQTLs) and DNA methylation quantitative trait loci (mQTLs) derived from whole blood, utilizing multi-omics SMR and Bayesian colocalization analysis. Considering the genetic differences of tissues, we replicated the shared causal signals of eQTLs and lung function in 48 diverse tissues and the shared causal signals of mQTLs and lung function in 8 diverse tissues. Multi-trait colocalization analyses were utilized to identify the causal signals between gene expression in blood, blood cell traits, and lung function, as well as between cross-tissue gene expression in diverse tissues and lung function.</p><p><strong>Results: </strong>Eight genes from blood tissue were prioritized as FEV1 causal genes using multi-omics SMR analysis and COLOC colocalization analysis: EML3, UBXN2A, ROM1, ZBTB38, RASGRP3, FAIM, PABPC4, and SNIP1. Equally, five genes (CD46, EML3, UBXN2A, ZBTB38, and LMCD1) were prioritized as FVC causal genes and one gene (LMCD1) was prioritized as FEV1/FVC causal genes. The causal signals between 8 genes (EML3, ROM1, UBXN2A, ZBTB38, RASGRP3, FAIM, PABPC4, and CD46) and lung function were successfully replicated in diverse tissues. More importantly, MOLCO colocalization analysis showed that 3 genes (CD46, LMCD1, and ZBTB38) expression in blood, blood cell traits, and lung function traits shared the same causal signals. Finally, through cross-tissue colocalization analysis of multiple traits, we found that the heart-lung axis EML3 expressions and lung function mediate the same causal signal.</p><p><strong>Conclusion: </strong>This study identified potential cross-tissue molecular targets associated with lung function traits from DNA methylation and gene expression of diverse tissues and explored the probable regulation mechanism of these molecular targets. This provides multi-omics and cross-tissue evidence for the molecular regulation mechanism of lung function and may provide new insight into the influence of crosstalk between organs and tissues on lung function.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"289"},"PeriodicalIF":3.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative mitogenomic analysis of Chinese cavefish Triplophysa (Cypriniformes: Nemacheilidae): novel gene tandem duplication and evolutionary implications.","authors":"Shuang Song, Jianhan Cao, Hongmei Xiang, Zhixiao Liu, Wansheng Jiang","doi":"10.1186/s12864-025-11486-0","DOIUrl":"10.1186/s12864-025-11486-0","url":null,"abstract":"<p><strong>Background: </strong>Cavefish exhibit significant morphological changes that result in trade-offs in metabolic requirements and energy utilization in perpetual darkness. As cellular \"powerhouses\", mitochondria play crucial roles in energy metabolism, suggesting that mitochondrial genes have likely experienced selective pressures during cavefish evolution.</p><p><strong>Results: </strong>This study presents the first assembly of the complete mitogenome of Triplophysa yangi, a typical cavefish species in China. The mitogenome is 17,068 bp long, marking the longest recorded for the genus Triplophysa, and includes 13 protein-coding genes (PCGs), 2 rRNAs, 25 tRNAs, and a noncoding control region. An ~ 500 bp insertion between ND2 and WANCY regions was observed, comprising a large intact tandem repeat unit (A'-N'-OL'-C') flanked by two unannotated sequences (U1/U2). The evolutionary origin of this repeat unit may involve either in situ duplication events with subsequent functional divergence-where neofunctionalization, subfunctionalization, or pseudogenization drove differential mutation rates between paralogs-or alternatively, horizontal acquisition from exogenous genetic material that became functionally integrated into the ancestral T. yangi mitogenome through co-option mechanisms. Phylogenetic analyses revealed two major clades within Triplophysa-epigean and hypogean lineages-consistent with previous classifications, while cave-restricted species exhibited signs of parallel evolution within the hypogean lineage. Selective pressure analysis indicated that the hypogean lineage (cave-dwelling groups, II & III) have a significantly increased ratio of nonsynonymous to synonymous substitution rates (ω) compared to the epigean lineage (surface-dwelling group, I), suggesting a combination of adaptive selection and relaxed functional constraints in cave-dwelling species.</p><p><strong>Conclusions: </strong>The duplication of tRNAs in T. yangi and the potential positive selection sites identified in Triplophysa cavefish further indicated adaptive evolution in mitochondrial PCGs in response to extreme subterranean conditions.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"293"},"PeriodicalIF":3.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of genomic tools to study and potentially improve the upper thermal tolerance of farmed Atlantic salmon (Salmo salar).","authors":"Eric H Ignatz, Melissa S Allen, Jennifer R Hall, Rebeccah M Sandrelli, Mark D Fast, Guy M L Perry, Matthew L Rise, A Kurt Gamperl","doi":"10.1186/s12864-025-11482-4","DOIUrl":"10.1186/s12864-025-11482-4","url":null,"abstract":"<p><strong>Background: </strong>The Atlantic salmon (Salmo salar) aquaculture industry must mitigate the impacts of rising ocean temperatures and the increased prevalence/severity of marine heat waves. Therefore, we investigated the genetic architecture and gene expression (transcriptomics) responsible for determining a salmon's upper thermal tolerance.</p><p><strong>Results: </strong>A genome-wide association study (GWAS) was conducted using fin clips of salmon from a previous incremental thermal maximum (IT_Max) challenge (n = 251) and the North American 50 K SNP chip. IT_Max was a highly polygenic trait with low/moderate heritability (mean SNP-based h² = 0.20 and pedigree-based h² = 0.25). Using data from the same fish, a separate GWAS assessed thermal-unit growth coefficient (TGC). Five significant SNPs were detected on chromosomes three and five, and high heritability estimates were calculated for TGC measured as fish grew from 12 to 20 °C (mean SNP-based h² = 0.62 and pedigree-based h² = 0.64). RNA-seq analyses of liver samples (n = 5-6 family^-1 temperature^-1) collected from the four most and four least tolerant families at 10 and 20 °C were also used to provide insights into potential mechanisms modulating this species' thermal tolerance. Between the top and bottom families, 347 and 175 differentially expressed transcripts (FDR-adjusted p < 0.01; fold-change ≥|2.0|) were identified at 10 and 20 °C, respectively. GO term enrichment analysis revealed unique responses to elevated temperature between family rankings (e.g., 'blood coagulation', 'sterol metabolic process' and 'synaptic growth at neuromuscular junction'). qPCR analyses further confirmed differences pertaining to cholesterol metabolism (lpl), inflammation (epx, elf3, ccl20), apoptosis (htra1b, htra2, anxa5b), angiogenesis (angl4, pdgfa), nervous system processes (insyn2a, kcnj11l) and heat stress (serpinh1b-1, serpinh1b-2). Three differentially expressed transcripts (i.e., ppp1r9a, gal3st1a, f5) were located in close proximity (± 120 kbp) to near-significant SNPs from the GWAS. Interestingly, ppp1r9a and gal3st1a have putative neurological functions, while f5 regulates blood coagulation.</p><p><strong>Conclusions: </strong>These analyses provide several putative biomarkers of upper thermal tolerance in salmon that could prove valuable in helping the industry develop more temperature-tolerant fish. Further, our study supports previous reports that IT_Max has low/moderate heritability in this species, and suggests that TGC at elevated temperatures is highly heritable.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"294"},"PeriodicalIF":3.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic insights into the genetic diversity and genetic basis of body height in endangered Chinese Ningqiang ponies.","authors":"Jiale Han, Hanrui Shao, Minhao Sun, Feng Gao, Qiaoyan Hu, Ge Yang, Halima Jafari, Na Li, Ruihua Dang","doi":"10.1186/s12864-025-11484-2","DOIUrl":"10.1186/s12864-025-11484-2","url":null,"abstract":"<p><strong>Background: </strong>Genetic diversity in livestock and poultry is critical for adapting production systems to future challenges. However, inadequate management practices, particularly in developing countries, have led to the extinction or near extinction of several species. Understanding the genetic composition and historical background of local breeds is essential for their effective conservation and sustainable use. This study compared the genomes of 30 newly sequenced Ningqiang ponies with those of 56 other ponies and 104 horses to investigate genetic diversity, genetic differentiation, and the genetic basis of body height differences.</p><p><strong>Result: </strong>Population structure and genetic diversity analyses revealed that Ningqiang ponies belong to southwestern Chinese ponies. They exhibit a moderate level of inbreeding compared to other pony and horse breeds. Mitochondrial DNA analysis indicated that Ningqiang and Debao ponies share the dominant haplogroups A and C, suggesting a likely common maternal origin. Our study identified low genetic differentiation and detectable gene flow between Ningqiang ponies and Datong horses. The study also indicated the effective population size of Ningqiang ponies showed a downward trend. These findings potentially reflect the historical formation of Ningqiang ponies and population size changes. A selection signal scan (CLR and θπ) within Ningqiang ponies detected several key genes associated with bone development (ANKRD11, OSGIN2, JUNB, and RPL13) and immune response (RIPK2). The combination of genome-wide association analysis and selective signature analysis (F_ST) revealed significant single nucleotide polymorphisms and selective genes associated with body height, with the most prominent finding being the TBX3 gene on equine chromosome (ECA) 8. Additionally, TBX5, ASAP1, CDK12, CA10, and CSMD1 were identified as important candidate genes for body height differences between ponies and horses.</p><p><strong>Conclusion: </strong>The results of this study elucidate the genetic diversity, genetic differentiation, and effective population size of Ningqiang ponies compared to other ponies and horses, further deepen the understanding of their small stature, and provide valuable insights into the conservation and breeding of local horse breeds in China.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"292"},"PeriodicalIF":3.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and functional validation of a novel FBN1 variant in a Marfan syndrome family using a zebrafish model.","authors":"Shitong Huang, Jiansong Chen, Qiuyu Wang, Ruyue Zhang, Jian Zhuang, Ruiyuan Huang, Changjiang Yu, Miaoxian Fang, Haishan Zhao, Liming Lei","doi":"10.1186/s12864-025-11471-7","DOIUrl":"10.1186/s12864-025-11471-7","url":null,"abstract":"<p><strong>Background: </strong>Marfan syndrome (MFS) is an inherited autosomal dominant disorder that affects connective tissue with an incidence of about 1 in 5,000 to 10,000 people. 90% of MFS is caused by mutations in the fibrillin-1 (FBN1) gene. We recruited a family with MFS phenotype in South China and identified a novel variant. This study investigated whether this genetic variant is pathogenic and the potential pathway related to lipid metabolism in MFS.</p><p><strong>Methods: </strong>A three-generation consanguineous family was recruited for this study. Whole exome sequencing (WES) was utilized on family members. The 3D structure of the protein was predicted using AlphaFold. CRISPR/Cas9 was applied to generate a similar fbn1 nonsense mutation (fbn1^+/-) in zebrafish. RNA-seq analysis on zebrafish was performed to identify potential pathways related to MFS pathogenesis.</p><p><strong>Results: </strong>Our study identified a novel variant [NM_000138.5; c.7764 C > G: p.(Y2588*)] in FBN1 gene from the family and identified the same site mutation among the proband along with her son and daughter. Structural modeling showed the p.Y2588* mutation resulted from a truncated protein. Compared to wild-type zebrafish, the F2 generation fbn1^+/- zebrafish exhibited MFS phenotype. RNA-seq analysis indicated that many genes related to leptin are up-regulating, which could affect bone development and adipose homeostasis.</p><p><strong>Conclusion: </strong>A novel variant was identified in FBN1 gene. In a zebrafish model, we found functional evidence supporting the pathogenicity of the detected nonsense mutation. Our research proposes a possible mechanism underlying the relationship between lipid metabolism and MFS. These findings can help improve the clinical diagnosis and treatment of MFS.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"288"},"PeriodicalIF":3.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}