Genes最新文献

{"title":"Molecular Identification of the Italian Soldiers Found in the Second World War Mass Grave of Ossero.","authors":"Barbara Di Stefano, Barbara Bertoglio, Filomena Melchionda, Monica Concato, Solange Sorçaburu Ciglieri, Alessandro Bosetti, Pierangela Grignani, Eros Azzalini, Yasmine Addoum, Raffaella Vetrini, Fabiano Gentile, Francesco Introna, Serena Bonin, Chiara Turchi, Carlo Previderè, Paolo Fattorini","doi":"10.3390/genes16030326","DOIUrl":"10.3390/genes16030326","url":null,"abstract":"<p><strong>Background/objectives: </strong>DNA analysis is the most reliable method for the identification of human skeletal remains, especially the ones found in mass disasters or recovered from mass graves. To this aim, DNA was extracted from bones and teeth allegedly belonging to 27 Italian soldiers executed during the Second World War and exhumed from a mass grave in Ossero (Croatia).</p><p><strong>Methods: </strong>A selection of 131 different bone samples (petrous bones, femurs, metacarpal, and metatarsal bones) and 16 molar teeth were used for DNA extraction. Autosomal and Y-chromosome STR profiles were determined using a conventional CE approach, while a panel of 76 microhaplotypes was investigated through MPS.</p><p><strong>Results: </strong>Overall, 24 different autosomal consensus male profiles and six (unexpected) female profiles were identified; the male profiles were then compared with 21 alleged living relatives of the missing soldiers belonging to 14 unrelated Italian families. The DVI module of the Familias software was used for computing the LRs and the posterior probabilities (PP). The combination of autosomal STRs and microhaplotypes led to the identification of six victims and to a very likely identification of another one, supported by Y-haplotype sharing between victim and relative. Three distant victim-relative relationships resulting in low LR values for the autosomal markers showed Y-STR haplotype-sharing patterns, thus suggesting very strong support for a paternal relationship.</p><p><strong>Conclusions: </strong>The results of this study confirmed the effectiveness of the genetic approach and highlighted the presence of more individuals than expected in the mass grave, among which six were female subjects.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729674","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":"Genomic Patterns of Homozygosity and Genetic Diversity in the Rhenish German Draught Horse.","authors":"Johanna Sievers, Ottmar Distl","doi":"10.3390/genes16030327","DOIUrl":"10.3390/genes16030327","url":null,"abstract":"<p><strong>Background/objectives: </strong>The Rhenish German draught horse is an endangered German horse breed, originally used as working horse in agriculture. Therefore, the objective of this study was to evaluate the breed's genetic diversity using pedigree and genomic data in order to analyze classical and ancestral pedigree-based inbreeding, runs of homozygosity, ROH islands, and consensus ROH.</p><p><strong>Methods: </strong>We studied the genome-wide genotype data of 675 Rhenish German draught horses and collated pedigree-based inbreeding coefficients for these horses. The final dataset contained 64,737 autosomal SNPs.</p><p><strong>Results: </strong>The average number of ROH per individual was 43.17 ± 9.459 with an average ROH length of 5.087 Mb ± 1.03 Mb. The average genomic inbreeding coefficient F_ROH was 0.099 ± 0.03, the pedigree-based classical inbreeding coefficient F_PED 0.016 ± 0.021, and ancestral inbreeding coefficients ranged from 0.03 (F_{a_Kal}) to 0.51 (Ahc). Most ROH (55.85%) were classified into the length category of 2-4 Mb, and the minority (0.43%) into the length category of >32 Mb. The effective population size (N_e) decreased in the last seven generations (~65 years) from 189.43 to 58.55. Consensus ROH shared by 45% of the horses were located on equine chromosomes 3 and 7, while ROH islands exceeding the 99th percentile threshold were identified on chromosomes 2, 3, 5, 7, 9, 10, and 11. These ROH islands contained genes associated with morphological development (<i>HOXB</i> cluster), fertility (<i>AURKC</i>, <i>NLRP5</i>, and <i>DLX3</i>), muscle growth, and skin physiology (<i>ZNF</i> gene cluster).</p><p><strong>Conclusions: </strong>This study highlights how important it is to monitor genetic diversity in endangered populations with genomic data. The results of this study will help to develop breeding strategies to ensure the conservation of the German Rhenish draught horse population and show whether favorable alleles from the overrepresented candidate genes within ROH were transmitted to the next generation.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729696","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":"Long-Term Phenotypic Evolution in GRIN2A-Related Disorders: Electroclinical and Genetic Insights from Two Families with Extended Follow-Up.","authors":"Ester Di Muro, Pietro Palumbo, Massimo Carella, Mario Benvenuto, Maria Rachele Bianchi, Umberto Costantino, Giovanni Di Maggio, Marco Castori, Giuseppe d'Orsi, Orazio Palumbo","doi":"10.3390/genes16030323","DOIUrl":"10.3390/genes16030323","url":null,"abstract":"<p><p><b>Background:</b> The <i>GRIN2A</i> gene and its product protein have been linked to a wide spectrum of neurodevelopmental disorders named <i>GRIN2A</i>-related disorders. Clinical presentation is highly variable and characteristically includes acquired cognitive, behavioral, and language impairment, as well as epilepsy, ranging from benign forms to severe epileptic encephalopathy. Recent genetic investigations have expanded the clinical spectrum of heterozygous <i>GRIN2A</i> variants, improving our understanding of genotype-phenotype correlations. However, there have been few long-term observational studies of patients affected by the genetically determined <i>GRIN2A</i>-related disease. <b>Methods:</b> To understand the long-term changes in clinical features, we described three patients from two Italian families, carrying variants in the <i>GRIN2A</i> gene. <b>Results:</b> After more than a decade of extensive electro-clinical follow-up, we observed a progressive cognitive decline associated with severe behavioral disturbances, despite clinical seizure control. The persistent presence of EEG epileptiform abnormalities over time suggests the need for a longitudinal neurophysiological study to monitor disease progression and evaluate the potential for anti-seizure medication discontinuation. <b>Conclusions:</b> Our study offers new insights into the natural progression of epilepsy in <i>GRIN2A</i>-related disorders, highlighting that a more detailed understanding of the phenotype and timely, personalized treatment could enhance the management and quality of life for both <i>GRIN2A</i> patients and their caregivers.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729640","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":"Short Exposures to Phosphine Trigger Differential Gene Expression in Phosphine-Susceptible and -Resistant Strains of <i>Tribolium castaneum</i>.","authors":"Christos G Athanassiou, Daniel Brabec, Morgan Olmstead, Nickolas G Kavallieratos, Brenda Oppert","doi":"10.3390/genes16030324","DOIUrl":"10.3390/genes16030324","url":null,"abstract":"<p><strong>Background/objectives: </strong>Phosphine resistance in insects involves a complex interplay of genetic and physiological factors, which are often poorly understood. Resistance to high concentrations of phosphine worldwide poses a formidable challenge for stored-product pest management and affects global food security. Understanding the genetic basis of phosphine resistance in the red flour beetle, <i>Tribolium castaneum</i>, is urgent because of the species' status as a notorious insect pest of stored grains and their resistance to major classes of insecticides. In this study, we take advantage of <i>T. castaneum</i> as a model species for biological and genetic studies.</p><p><strong>Methods: </strong>To tease apart genetic mutations and the differential expression of genes responding to phosphine intoxication, we set up 16 different exposure tests to compare the effects of phosphine dose, exposure time, and sampling time on gene expression in phosphine-susceptible and -resistant <i>T. castaneum</i> adults.</p><p><strong>Results: </strong>We examined the enrichment of gene ontology terms in genes that were differentially expressed and found that the data further distinguished differences in gene expression by insect strain, phosphine dose, exposure time, and recovery from phosphine exposure. The gene-encoding cytochrome P450 9e2 was expressed more in phosphine-resistant compared to phosphine-susceptible insects under all treatment conditions and was significantly higher in expression in resistant insects that were sampled after short or long phosphine exposures. Therefore, this gene may serve as a new phosphine resistance marker in <i>T. castaneum</i> and can further be utilized as a diagnostic tool for resistance detection.</p><p><strong>Conclusions: </strong>These data are important to understand the complex molecular changes in insects that have reduced sensitivity to phosphine to develop new monitoring and resistance prevention strategies.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729737","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":"Genome-Wide Identification and Comprehensive Analysis of the GARP Transcription Factor Superfamily in <i>Populus deltoides</i>.","authors":"Qin Yang, Zhengquan He, Chenjia Zheng, Ruoyu He, Yu Chen, Renying Zhuo, Wenmin Qiu","doi":"10.3390/genes16030322","DOIUrl":"10.3390/genes16030322","url":null,"abstract":"<p><p><b>Background/Objectives:</b> The GARP transcription factor superfamily is crucial for plant growth, development, and stress responses. This study systematically identified and analyzed the <i>GARP</i> family genes in <i>Populus deltoides</i> to explore their roles in plant development and abiotic stress responses. <b>Methods:</b> A total of 58 <i>PdGARP</i> genes were identified using bioinformatics tools. Their physicochemical properties, genomic locations, conserved motifs, gene structures, and phylogenetic relationships were analyzed. Expression patterns under phosphorus and nitrogen deficiency, as well as tissue-specific expression, were investigated using RT-qPCR. Transgenic RNAi lines were generated to validate the function of <i>GLK</i> genes in chlorophyll biosynthesis. <b>Results:</b> The 58 <i>PdGARP</i> genes were classified into five subfamilies based on their evolutionary relationships and protein sequence similarity. Segmental duplication was found to be the primary driver of the PdGARP family's expansion. <i>Cis</i>-regulatory elements (CREs) related to light, hormones, and abiotic stresses were identified in the promoters of <i>PdGARP</i> genes. Differential expression patterns were observed for NIGT1/HRS1/HHO and PHR/PHL subfamily members under phosphorus and nitrogen deficiency, indicating their involvement in stress responses. KAN subfamily members exhibited tissue-specific expression, particularly in leaves. Structural analysis of the GLK subfamily revealed conserved α-helices, extended chains, and irregular coils. Transgenic RNAi lines targeting <i>GLK</i> genes showed significant reductions in chlorophyll and carotenoid content. <b>Conclusions:</b> This study provides a comprehensive analysis of the GARP transcription factor superfamily in <i>P. deltoides</i>, highlighting their potential roles in nutrient signaling and stress response pathways. The findings lay the foundation for further functional studies of <i>PdGARP</i> genes and their application in stress-resistant breeding of poplar.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729688","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":"A Comparative Analysis and Phylogenetic Relationship of the Chloroplast Genome Sequences of <i>Illicium verum</i> and <i>Illicium difengpi</i>.","authors":"Suqin Guo, Xiqun Wu, Feng Peng, Kun Zhang, Suren Rao Sooranna, Guiyu Tan","doi":"10.3390/genes16030321","DOIUrl":"10.3390/genes16030321","url":null,"abstract":"<p><p><b>Background/Objectives:</b><i>Illicium verum</i> Hook. f. and <i>Illicium difengpi</i> K. I. B.et K. I. M. are two important medicinal plants which grow in the mountainous areas of Guangxi, China. Their similar morphological characteristics frequently lead to their misidentification. Chloroplast genome (cp)-based barcode technology has been used to effectively identify two closely related species; however, at present, there is no systematic comparative study of the cp genome sequences between <i>I. verum</i> and <i>I. difengpi</i>. <b>Methods</b>: Here, the cp genomes of the two plants were sequenced and analyzed. <b>Results</b>: The cp genome sizes were 142,689 and 142,689 bp for <i>I. verum</i> and <i>I. difengpi</i>, respectively. Each of the cp genomes annotated 122 genes, with 79 protein coding genes, 8 ribosomal RNA genes, and 35 transfer RNA genes. Amino acid frequencies of 1.17-10.19% (<i>I. verum</i>) and 1.18-10.17% (<i>I. difengpi</i>) were found in the coding genes. There were also 104 and 96 SSRs as well as 26 and 25 long repeats identified in <i>I. verum</i> and <i>I. difengpi</i>, respectively, among which the most common were A/T base repeats. Both cp genomes had SSC/IRa junctions located in gene <i>ycf1-trnN.</i> The <i>ycf1</i> and <i>trnL-trnV-rps7</i> genes were positioned at the IRb/SSC and LSC/IR boundaries, respectively. A phylogenetic relationship was constructed and the two species were fully nested within the genus <i>Illicium</i>. <b>Conclusions</b>: The comparative cp genomes of <i>I. verum</i> and <i>I. difengpi</i> are presented in this study, and this provides valuable phylogenetic information for subsequent molecular marker development and research of <i>I. verum</i> and <i>I. difengpi</i>.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729557","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":"Interstitial 1q Deletion Syndrome: A New Patient with Congenital Diaphragmatic Hernia and Multiple Midline Anomalies.","authors":"Gregorio Serra, Rosaria Nardello, Vincenzo Antona, Maria Rita Di Pace, Alessandra Giliberti, Mario Giuffrè, Daniela Mariarosa Morreale, Ettore Piro, Ingrid Anne Mandy Schierz, Maria Sergio, Giuseppina Valenti, Marco Pensabene, Giovanni Corsello","doi":"10.3390/genes16030319","DOIUrl":"10.3390/genes16030319","url":null,"abstract":"<p><strong>Background: </strong>Interstitial deletions of chromosome 1q are rare, with about 30 cases reported in the literature. The phenotypical features of the affected subjects described so far include microcephaly, pre- and post-natal growth retardation, psychomotor delays, ear anomalies, brachydactyly, in addition to small hands and feet, and rarely a congenital diaphragmatic hernia (CDH).</p><p><strong>Case presentation: </strong>Here, we report on a neonate with CDH, dysmorphic features, and multiple midline anomalies including a cleft palate, in whom an array-comparative genomic hybridization (a-CGH) analysis allowed the identification of an interstitial deletion of the long arm of chromosome 1. Our patient underwent a surgical correction of CDH on the fourth day of life, while that of cleft palate has been planned to be performed at 12 months.</p><p><strong>Conclusions: </strong>The few subjects suffering such rearrangement reported to date, along with the clinical and genetic profile of the present newborn, show that 1q deletions should be considered within the context of the \"interstitial 1q deletion syndrome\". Comparing our case with those described in previous studies, the involved genomic regions and the phenotypic traits are partially overlapping, although the clinical picture of the present patient is among the few ones including a congenital diaphragmatic hernia within the phenotypical spectrum. A more extensive comparative analysis of a larger number of patients with similar genetic profiles may allow for a more precise clinical and genomic characterization of this rare syndrome, and for genotype-phenotype correlations.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729561","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":"Genome-Wide Runs of Homozygosity Reveal Inbreeding Levels and Trait-Associated Candidate Genes in Diverse Sheep Breeds.","authors":"Rui Ma, Jiaxin Liu, Xiao Ma, Ji Yang","doi":"10.3390/genes16030316","DOIUrl":"10.3390/genes16030316","url":null,"abstract":"<p><strong>Background: </strong>Quantifying and controlling the inbreeding level in livestock populations is crucial for the long-term sustainability of animal husbandry. However, the extent of inbreeding has not been fully understood in sheep populations on a global scale.</p><p><strong>Methods: </strong>Here, we analyzed high-depth genomes of 210 sheep from 20 worldwide breeds to identify the pattern and distribution of genome-wide runs of homozygosity (ROH) and detect candidate selected genes in ROH islands for agronomic and phenotypic traits.</p><p><strong>Results: </strong>Leveraging whole-genome sequencing data, we found a large number of short ROH (e.g., <1.0 Mb) in all breeds and observed the overall higher values of ROH statistics and inbreeding coefficient in European breeds than in Asian breeds and Dorper sheep. We identified some well-known candidate genes (e.g., <i>CAMK4</i>, <i>HOXA</i> gene family, <i>ALOX12</i>, <i>FGF11</i>, and <i>MTOR</i>) and 40 novel genes (e.g., <i>KLHL1</i>, <i>FGFRL1</i>, <i>WDR62</i>, <i>GDF6, KHDRBS2</i>, and <i>PAX1</i>) that are functionally associated with fecundity, body size, and wool-related traits in sheep. Based on the candidate genes, we revealed different genetic bases for the fecundity traits of European and Asian sheep.</p><p><strong>Conclusions: </strong>This study improves the resolution of ROH detection and provides new insights into genomic inbreeding and trait architecture in sheep as well as useful markers for future breeding practice.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729694","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":"Genome-Wide Identification and Expression Pattern of the <i>NAC</i> Gene Family in <i>Panax notoginseng</i>.","authors":"Baihui Jin, Xiaolong Hu, Na Li, Xiaohua Li, Zebin Chen, Xinyu Zhao, Xiaoni Wu","doi":"10.3390/genes16030320","DOIUrl":"10.3390/genes16030320","url":null,"abstract":"<p><strong>Background: </strong>The NAC transcription factor family of genes is one of the largest families of transcription factors in plants, playing important functions in plant growth and development, response to adversity stress, disease resistance, and hormone signaling. In this study, we identified the number of members of the <i>Panax notoginseng</i> NAC (<i>PnNAC</i>) gene family and conducted a comprehensive analysis of their physicochemical characteristics, chromosomal location, evolutionary features, and expression patterns both in different parts of the plant at different growth stages and in response to infection by <i>Alternaria panax</i>.</p><p><strong>Methods: </strong>The <i>NAC</i> gene family in <i>P. notoginseng</i> was identified using Hidden Markov Model (HMMER) and National Center of Biotechnology Information Conserved Domain Database (NCBI CDD), and their physicochemical properties were analyzed with Perl scripts. Phylogenetic relationships were determined using Clustal Omega and FastTree, and gene structures were visualized with an R script. Promoter regions were analyzed with PlantCARE, motifs with MEME and ggmotif, and transcriptome data were processed using Hical Indexing for Spliced Alignment of Transcripts (HISAT2) and HTseq.</p><p><strong>Results: </strong>This study identified 98 PnNAC genes in <i>P. notoginseng</i>, analyzed their characteristics (protein lengths 104-882 aa, molecular weights 11.78-100.20 kDa, isoelectric points 4.12-9.75), location (unevenly distributed on 12 chromosomes, no tandem repeats), evolution, and expression patterns (distinct in different parts, growth stages, and after <i>A. panax</i> infection).</p><p><strong>Conclusions: </strong><i>PnNAC</i> plays an important role in the growth and development of <i>P. notoginseng</i> and in its response to <i>A. panax</i>. <i>PnNAC</i> could be a candidate gene for further research on and functional analysis of <i>P. notoginseng</i> disease resistance.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729691","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":"Cryptic <i>KMT2A::AFDN</i> Fusion Due to <i>AFDN</i> Insertion into <i>KMT2A</i> in a Patient with Acute Monoblastic Leukemia.","authors":"Qing Wei, Gokce A Toruner, Beenu Thakral, Keyur P Patel, Naveen Pemmaraju, Sa A Wang, Rashmi Kanagal-Shamanna, Guilin Tang, Ghayas C Issa, Sanam Loghavi, L Jeffrey Medeiros, Courtney DiNardo","doi":"10.3390/genes16030317","DOIUrl":"10.3390/genes16030317","url":null,"abstract":"<p><strong>Background: </strong><i>KMT2A</i> rearrangements occur in ~10% of acute myeloid leukemia (AML) cases and are critical for classification, risk stratification, and use of targeted therapy. However, insertions involving the <i>KMT2A</i> gene can evade detection using chromosomal analysis and/or fluorescence in situ hybridization (FISH).</p><p><strong>Methods: </strong>We present a case of a 22-year-old woman with acute monoblastic leukemia harboring a cryptic <i>KMT2A::AFDN</i> fusion identified by RNA sequencing. Initial FISH showed a 3' <i>KMT2A</i> deletion, while conventional karyotyping and the automated bioinformatic pipeline for optical genome mapping (OGM) did not identify the canonical translocation.</p><p><strong>Results: </strong>To resolve these discrepancies, metaphase <i>KMT2A</i> FISH (break-apart fusion probe) was performed to assess whether <i>KMT2A</i> was translocated to another chromosome. However, the results did not support this possibility. As the fusion signal remained on the normal chromosome 11, with the 5' <i>KMT2A</i> signal localized to the derivative chromosome 11. A subsequent manual review of the OGM data revealed a cryptic ~300 kb insertion of <i>AFDN</i> into the 3' region of <i>KMT2A</i>, reconciling the discrepancies between chromosomal analysis, FISH, and RNA fusion results.</p><p><strong>Conclusions: </strong>This case highlights the importance of integrating multiple testing modalities with expert review when there is a discrepancy. Our findings emphasize the need for a comprehensive approach to genomic assessment to enhance diagnostic accuracy and guide therapeutic decision-making.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729591","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}