Molecular Genetics and Genomics最新文献

{"title":"Unraveling genetic diversity and population structure of pineapple germplasm using genome-wide SNP markers.","authors":"Haomin Lyu, Tracie Matsumoto, Qingyi Yu","doi":"10.1007/s00438-025-02275-1","DOIUrl":"10.1007/s00438-025-02275-1","url":null,"abstract":"<p><p>Pineapple (Ananas comosus (L.) Merr.) is one of the most important tropical fruits worldwide. It is primarily propagated clonally and exhibits high heterozygosity which can mask deleterious mutations, potentially leading to inbreeding depression and hindering breeding efforts. To address this, we conducted a comprehensive genome-wide analysis of 91 pineapple accessions and identified over 7.9 million high-quality SNPs. We utilized these SNPs to investigate the genetic structure and reproductive patterns of diverse cultivars and related varieties. Population structure analysis revealed a unique genetic makeup of A. comosus var. microstachys accessions and unidirectional gene flow from A. comosus var. microstachys into A. comosus var. comosus, A. comosus var. bracteatus, and A. comosus var. erectifolius. Among the cultivated pineapples, 'Mordilona-related' and 'Smooth Cayenne' cultivars showed unidirectional gene flow from 'Singapore Spanish', 'Queen', and the wild A. comosus var. microstachys. Heterozygosity patterns suggested predominantly asexual reproduction in 'Queen', 'Singapore Spanish', 'Smooth Cayenne', and A. comosus var. microstachys populations, while 'Mordilona-related' and A. comosus var. bracteatus populations might have experienced increased sexual reproduction or population expansion. We developed two SNP panels: one for germplasm identification and the other one for pedigree analysis. These resources will facilitate pineapple germplasm evaluation, diversity analysis, and informed breeding decisions for cultivar improvement.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"300 1","pages":"71"},"PeriodicalIF":2.3,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12276139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering gonadal transcriptome reveals circRNA-miRNA-mRNA regulatory network involved in sex differentiation and gametogenesis of Apostichopus japonicus.","authors":"Ziming Li, Xinyue Tang, Xinghai Liu, Jing Huo, Ying Guo, Yujia Yang","doi":"10.1007/s00438-025-02276-0","DOIUrl":"https://doi.org/10.1007/s00438-025-02276-0","url":null,"abstract":"<p><p>As stable and conserved non-coding RNAs, circular RNAs (circRNAs) play vital roles in gene regulation, particularly in reproductive development. However, their functions in marine invertebrate gonadal differentiation remain largely unexplored. Understanding the molecular mechanisms of sexual differentiation and gonadal development is essential for advancing reproductive biology in marine invertebrates. The sea cucumber Apostichopus japonicus is a vital species in economic aquaculture. Before the breeding season, A. japonicus exhibits minimal sexual dimorphism, significantly impeding breeding efficiency and posing challenges for the development of superior germplasm resources. Investigating the role of circRNAs in mature A. japonicus will enhance our understanding of its specific molecular mechanism during sexual differentiation and gonadal reproduction. In this study, we constructed differential expression profiles of circRNAs. A total of 18,121 circRNAs were identified, distributed across the 23 chromosomes of A. japonicus. 584 circRNAs exhibited significant expression differences, with 296 up-regulated and 288 down-regulated. Through GO enrichment and KEGG pathway analysis of these circRNAs, two pathways related to sexual differentiation were identified: the AMPK signaling pathway and the TGF-β signaling pathway, which may regulate sexual differentiation by influencing sex hormone synthesis. Additionally, several genes, such as smad3, smoc2, and ppp2r1a may play critical regulatory roles in the development and activity of germ cells. Our study elucidates the molecular regulatory roles of circRNAs in the sexual differentiation and gonadal development of A. japonicus. Given its evolutionary position as the closest phylum to chordates, the present study on A. japonicus provides valuable insights into the non-coding RNA resource for marine invertebrates.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"300 1","pages":"70"},"PeriodicalIF":2.3,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular breeding for stress tolerance in sesame.","authors":"Micheale Yifter Weldemichael, Hailay Mehari Gebremedhn, Steven Runo, Harish Gandhi","doi":"10.1007/s00438-025-02274-2","DOIUrl":"https://doi.org/10.1007/s00438-025-02274-2","url":null,"abstract":"<p><p>Sesame (Sesamum indicum L.) is a vital oilseed crop known for its high-quality edible oil, proteins, minerals, and vitamins. It is primarily cultivated in arid and semi-arid regions, where unpredictable drought poses a major constraint to its production. Sesame is a valuable source of healthy vegetable oil, attracting growing interest worldwide. However, its cultivation in dry regions makes it vulnerable to various biotic and abiotic stresses. Sesame is grown for food, pharmaceutical, medicinal, and industrial uses, which is cultivated as a main cash crop by African and Asian smallholder farmers. Despite its importance, sesame production and productivity remain low due to numerous challenges such as; drought, salinity, diseases, insect pests, inherent genetic problems, and poor agronomic and postharvest practices. Fortunately, the crop's extensive genetic diversity offers potential for enhancing stress resilience. Our understanding of sesame molecular responses will be facilitated by ongoing attempts to develop methods for quantifying biotic and abiotic stresses. We review recent advances in the molecular mechanisms underlying sesame's tolerance to biotic and abiotic stresses focusing on stress-related genes and key agronomic traits. Additionally, we review recent advancements in functional genomics and transcriptomics, specifically in deciphering sesame's responses to drought, water-logging, temperature fluctuations, osmotic stress, and salinity as well as biotic stressors. To accelerate the development of stress-resistant sesame varieties, we propose advancing research in genomics-assisted breeding. Approaches such as genome-wide association studies (GWAS) and high-density linkage mapping can help identify key genetic markers associated with stress tolerance. These markers can then be applied in marker-assisted selection to develop resilient cultivars, ensuring stable yields under changing climate conditions.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"300 1","pages":"69"},"PeriodicalIF":2.3,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unravelling the genomic landscape of Acinetobacter baumannii: deep dive into virulence factors, resistance elements, and evolutionary adaptations.","authors":"Mohammad Sholeh, Faezeh Hamidieh, Masoumeh Beig, Farzad Badmasti","doi":"10.1007/s00438-025-02265-3","DOIUrl":"https://doi.org/10.1007/s00438-025-02265-3","url":null,"abstract":"<p><p>The increasing prevalence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Acinetobacter baumannii presents a major global health threat, particularly in hospital settings. Understanding the genomic landscape of A. baumannii is essential to elucidate its virulence mechanisms, resistance profiles, and evolutionary adaptations, which are critical for developing novel therapeutic strategies. This study aims to comprehensively analyze the pan-genome, antimicrobial resistance (AMR) genes, virulence factors, and clonal relationships of A. baumannii, with the goal of uncovering insights into its pathogenicity and genomic evolution. A total of 27,884 A. baumannii genomes were retrieved from GenBank for analysis. Genome annotation was carried out using Prokka, and pan-genome analysis was performed with Roary. AMR genes and virulence factors were identified through AMRFinderPlus and the Virulence Factor Database via Abricate. Temporal trends in AMR and virulence were analyzed statistically to assess changes over time. The study found that A. baumannii possesses a stable core genome and a highly diverse accessory genome, suggesting an open pan-genome structure. Temporal analysis revealed a significant increase in AMR genes, including bla_OXA-23, bla_NDM-1, and pmrCAB. Virulence genes were widely distributed across strains, with the sequence types (ST) like ST2^Pas clone exhibiting global dissemination, highlighting the strain's potential for widespread pathogenicity. This comprehensive genomic analysis of A. baumannii reveals its significant genomic diversity and adaptability, underscoring the critical role of both core and accessory genomes in shaping its pathogenicity and resistance mechanisms. The increasing prevalence of key AMR genes, alongside the widespread dissemination of virulent clones, highlights the urgent need for enhanced surveillance and novel therapeutic strategies to control the spread of this global pathogen. Future research should focus on the functional characterization of resistance and virulence factors to better understand their roles in pathogenicity and to facilitate the development of targeted interventions against A. baumannii.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"300 1","pages":"68"},"PeriodicalIF":2.3,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic analysis of terpene synthase family and characterization of ent-kaurene synthase in Chenopodium quinoa.","authors":"Shuaibing Tian, Liping Wang, Lijun Liu, Xiaoyu Sha, Jine Wu, Jingye Fu, Qiang Wang","doi":"10.1007/s00438-025-02269-z","DOIUrl":"https://doi.org/10.1007/s00438-025-02269-z","url":null,"abstract":"<p><p>Terpenoids produced in plants play important roles in growth, development and response to environmental stimuli. Terpene synthases are responsible for the terpene backbone formation of terpenoid metabolites. In this study, fifty-one terpene synthase genes were identified in the quinoa genome and categorized into seven sub-families through bioinformatics and phylogenetic analysis. Gene structures, conserved motifs and cis-elements in promoters were also analyzed for these CqTPSs, as well as prediction of secondary and tertiary protein structure. Four terpene synthase genes in the TPS-e sub-family were further cloned for functional characterization. Among which, CqTPS49 and CqTPS51 were detected to react with ent-CPP to generate ent-kaurene, the intermediate of gibberellin biosynthesis, subsequently name as CqTPS49/KS1 and CqTPS51/KS2, respectively. CqTPS47 and CqTPS48 reacted with syn-CPP to form diterpene products, which needs to be identified with chemical structure characterization. All four tested CqTPSs were found to be localized in the chloroplast, consistent with their functions as diterpene synthease. Expression patterns analysis in different tissues revealed that CqTPS49/KS1 and CqTPS51/KS2 are mainly expressed in the active growing buds, suggesting involvement in gibberellic acid metabolism. This study identified the terpene synthase gene family in quinoa and provided the basis for further functional characterization of terpenoid metabolism.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"300 1","pages":"66"},"PeriodicalIF":2.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A reference genome for Plinia edulis: expanding the pharmacological and nutraceutical potential of a neglected brazilian tree species.","authors":"Valdir Marcos Stefenon, Thiago Sanches Ornellas, Yohan Fritsche, Suelen Martinez Guterres, Ingrid Lohani Degering Brand, Ana Kelly de Sousa Silva, Fernando Joner","doi":"10.1007/s00438-025-02268-0","DOIUrl":"https://doi.org/10.1007/s00438-025-02268-0","url":null,"abstract":"<p><p>Widely distributed in tropical and subtropical regions, the Myrtaceae family includes several species with vast nutraceutical potential due to their rich composition of bioactive compounds with pharmacological and nutraceutical importance. Plinia edulis is a neglected and endangered Myrtaceae species of the Brazilian Atlantic Forest, with tasteful nutraceutical fruits and potential use in the pharmacological industry. Here we report the sequencing, assembling, and annotation of a reference genome for this species, towards stimulating its conservation, cultivation, domestication, and genetic improvement. The reference genome presented 98.5% BUSCO completeness, N50 = 21.2 Mb, and 37.428 gene models predicted. These gene models are related to 327 pathways of secondary metabolites biosynthesis, including 59 of terpenoids and polyketides and 40 of propanoids and flavonoids metabolism. The KEGG mapping revealed key genes for producing 20 important secondary metabolites with pharmacological significance, enlarging the opportunities for nutraceutical and pharmacological uses of the species. The prospection of SSR markers allowed primer design for 30,897 loci, of which about 75% are potentially informative for SSR and SSRseq analysis. This reference genome will assist conservation and genetic breeding programs, and the annotation will support studies on secondary metabolite production. Genetic conservation and breeding projects for P. edulis may also consider the revealed genomic potential of this species to react to environmental stresses.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"300 1","pages":"67"},"PeriodicalIF":2.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kenaf cyclic nucleotide-gated channel gene HcCNGC27 confers plant drought stress tolerance and involved in flowering regulation.","authors":"Canni Chen, Huiping Xiao, Jiao Yue, Xu Wang, Caijin Wang, Rujian Wei, Dengjie Luo, Peng Chen","doi":"10.1007/s00438-025-02272-4","DOIUrl":"https://doi.org/10.1007/s00438-025-02272-4","url":null,"abstract":"<p><p>Cyclic Nucleotide-Gated Channel (CNGC) gene consists a large family and plays an important role in plant growth and development, biotic and abiotic stresses, yet their functions in non-model crops like kenaf (Hibiscus cannabinus L.), a highly stress-resistant bast fiber crop, remain poorly understood. To investigate the role in kenaf abiotic stress response and plant development regulation, we characterized the HcCNGC27 gene in kenaf. Our study aimed to elucidate the role of HcCNGC27 in drought stress response and its impact on plant development. HcCNGC27 was identified subcellularly localized to the plasma membrane. Expression analysis showed that HcCNGC27 is ubiquitously expressed across various tissues including roots, stems, leaves, flowers, and seeds, with the highest expression observed in flowers. Importantly, HcCNGC27 was significantly induced under drought stress conditions. To investigate the function of HcCNGC27, we performed virus-induced gene silencing (VIGS) in kenaf and overexpression in Arabidopsis thaliana. Silencing of HcCNGC27 in kenaf resulted in a dwarf phenotype and reduced drought stress tolerance, evidenced by decreased antioxidant enzyme activities, increased reactive oxygen species (ROS) accumulation, and decreased osmoregulatory substances content. Additionally, the expression levels of antioxidant enzyme-related genes and stress-responsive genes were markedly down-regulated in the silenced lines. Conversely, overexpression of HcCNGC27 in Arabidopsis thaliana enhanced drought stress tolerance, characterized by stronger protective enzyme activity, better ROS scavenging capacity, improved osmotic adjustment, higher total chlorophyll content, lower death rate, and significant up-regulation of stress-responsive genes. Moreover, overexpression of HcCNGC27 delayed flowering in Arabidopsis thaliana, as indicated by qRT-PCR analysis showing significant down-regulation of AtFT and AtSOC1 and up-regulation of AtFLC in the overexpression lines compared to wild-type controls. In summary, HcCNGC27 emerges as a dual-function regulator enhancing drought tolerance via ROS scavenging and osmotic adjustment while delaying flowering may through modulation of the FT/SOC1/FLC pathway.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"300 1","pages":"65"},"PeriodicalIF":2.3,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GSK343, an inhibitor of EZH2, prevents acquired cisplatin resistance in bladder cancer.","authors":"Liang He, Peng Liu","doi":"10.1007/s00438-025-02273-3","DOIUrl":"10.1007/s00438-025-02273-3","url":null,"abstract":"<p><p>Epigenetic alterations are emerging as a major driver of acquired cisplatin (CDDP) resistance in bladder cancer (BCa). The study investigated whether GSK343, an inhibitor of Enhancer of Zeste Homolog 2 (EZH2), can overcome CDDP resistance in BCa. CDDP-resistant T24 and 5637 cells were treated GSK343 (5, 10, or 20µM) for 48 h. Cell viability was assessed using CCK-8 assays, clonogenic survival using colony formation assays, migration capacity using wound healing (scratch) assays, invasion using Transwell assays, and apoptosis using flow cytometry. CDDP-resistant cells exhibited significantly higher EZH2 and H3K27me3 expression levels than parental T24 and 5637 cells. Treatment with 20 µM GSK343 markedly reduced EZH2 and H3K27me3 expression in resistant cells compared to vehicle control, with greater efficacy than lower concentrations (5 or 10 µM). Following 20 µM GSK343 treatment, resistant cells showed significantly reduced viability, fewer colonies, impaired migration, and decreased invasion compared to vehicle control. Furthermore, the apoptosis rate was significantly increased in resistant cells treated with 20 µM GSK343. The study demonstrates that GSK343 inhibits EZH2-mediated H3K27me3 and overcomes acquired CDDP resistance in BCa cells, suggesting its therapeutic potential for BCa patients with limited benefit from chemotherapy.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"300 1","pages":"63"},"PeriodicalIF":2.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromosome scale assembly unveils genomic structure and gene families of Calotropis procera.","authors":"Hari Shankar Gadri, Sarbani Roy, Saneha Devi, Jigmet Chuskit Angmo, Vikas Sharma, Mohammed Asif Chowdhary, Rohini Dwivedi, Pankaj Bhardwaj","doi":"10.1007/s00438-025-02270-6","DOIUrl":"https://doi.org/10.1007/s00438-025-02270-6","url":null,"abstract":"<p><p>Calotropis procera (Akra, 2n = 22) is a fast-growing, fiber-producing, and climate-resilient, yet underexplored for domestication. The significant step forward in the domestication of this invaluable plant species marks the development of a reference genome. The study reveals a chromosome-scale genome that anchors 11 chromosomes, with a reference assembly spanning approximately 202.83 Mb. It contains few repetitive sequences, accounting for only 5% of the total genome. C. procera display a significant pair-orthology dN/dS ratio of nearly 0.2 to 0.25, indicating strong conservation, purifying selection, and resistance to harsh conditions. C. procera experienced phylogenetic relations with familiar sister genera divergent around 38.5 million years ago. The chromosomal structural rearrangement endured alterations throughout divergence due to a synteny interaction with the genomes of A. syriaca. The findings delve into the role of gene families in the adaptive evolutionary processes of C. procera. The study enhanced our comprehension of genome biology, the influence of gene families on adaptation. The genome research is invaluable and will significantly influence the future domestication of C. procera.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"300 1","pages":"64"},"PeriodicalIF":2.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced identification of novel pathogenic variants in hereditary hearing loss through physical phasing with integrated short and long-read sequencing data.","authors":"Lu Kang, Qian Zhang, Chao Wang, Jia Geng, Xinlei Li, Mingjun Zhong, Sihan Liu, Xuegang Wang, Yu Lu, Jing Cheng, Yongxin Ma, Fengxiao Bu, Huijun Yuan","doi":"10.1007/s00438-025-02256-4","DOIUrl":"10.1007/s00438-025-02256-4","url":null,"abstract":"<p><p>Haplotagged variant calling is essential for determining genetic etiologies in hereditary hearing loss (HHL) cases when familial testing is unavailable, and long-read whole-genome sequencing (lrWGS) enables this by outperforming in several key areas: enhanced detection of structural variations (SVs) and precise long-range haplotype phasing. In this study, we enrolled two HL cases from the China Deafness Genetics Consortium (CDGC) cohort, whose genetic tests were previously inconclusive due to a lack of pedigree segregation data. Small variants (including SNVs and InDels) profiles were generated by short-read whole-genome sequencing (srWGS), while SVs were identified and co-phased with small variants using a read-based approach. As a result, 87% and 83% of the chromosomal regions were successfully phased, and reached mean haplotype block lengths up to 661.9 kb and 309.9 kb, respectively. A total of 483 and 434 small variants, along with three and six heterozygous SVs in coding and splice regions of 201 HL-associated genes were phased. Pathogenic interpretations resolved compound heterozygosity in MARVELD2, identifying a pathogenic (P) variant NM_001038603.3:c.782G > A in trans with a novel pathogenic (P) deletion (NM_001038603.3:c.1183-1288_1503 + 195del). Additionally, we identified a known P variant NM_022124.6:c.5369-1G > A, which was oriented in trans with a P deletion NM_022124.6:c.-5-12_67 + 154del in the CDH23 gene. This study demonstrates the clinical utility of integrating srWGS and Nanopore lrWGS for comprehensive variant detection and haplotype determination in HL cases with limited family background details, providing a robust framework for resolving complex genetic etiologies and improving diagnostic precision.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"300 1","pages":"61"},"PeriodicalIF":2.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}