Frontiers in Genetics最新文献

{"title":"The \"mobile bricks\" of human evolution: how transposable elements shaped human phenotypes.","authors":"Giorgia Modenini, Paolo Abondio","doi":"10.3389/fgene.2026.1937765","DOIUrl":"10.3389/fgene.2026.1937765","url":null,"abstract":"<p><p>Far from being \"junk\" and devoid of function, transposable elements have been identified as players in genomes evolution and regulation, and are also used as valuable genetic markers to study population differentiation. Here we present a detailed review on how transposons participated in human evolution: from adaptation to extreme environments and response to both internal and external stressors, to phenotypes directly emerging from transposon mobilization activities. We dedicate a section to brain plasticity and neuronal differentiation, highlighting the possible role of transposable elements in neuro-psychiatric disorders in the context of emerging hypotheses such as the <i>genomic trade-off</i> and <i>price-to-pay</i>. Furthermore, we discuss methods and approaches to study the influence of transposable elements on human evolution, covering challenges to include ancient DNA in these studies. To conclude, we propose that transposons are not mere \"background noise\" in host genomes, but that they can be seen as genetic regulators of human phenotypes.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"17 ","pages":"1937765"},"PeriodicalIF":3.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13690969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149244335","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":"Distinct host genetic determinants of HIV acquisition and disease progression: the case of classical <i>HLA</i> class I.","authors":"Marion Amujal, James Bumba","doi":"10.3389/fgene.2026.1982540","DOIUrl":"https://doi.org/10.3389/fgene.2026.1982540","url":null,"abstract":"<p><p>HIV acquisition and disease progression appear to be influenced by largely distinct host genetic factors. Whether infection becomes established is determined shortly after mucosal or parenteral exposure, before HIV-specific CD8⁺ T-cell responses become detectable. Progression is shaped by immune responses acting after infection is established and is strongly influenced by classical <i>HLA</i> class I variation. <i>CCR5Δ32</i> affects both phenotypes, raising the possibility of shared determinants, but evidence for genetic overlap remains limited. Here, we review evidence on whether classical <i>HLA</i> class I variation is associated with HIV acquisition across diverse exposure routes and study designs. A large collaborative genome-wide association study (GWAS) found no significant association between <i>HLA</i> class I variation and HIV acquisition after accounting for frailty bias, and candidate-gene associations have not been independently replicated. Future research should prioritize well-characterized exposure cohorts and sequencing approaches capable of detecting structural variation and resolving complex loci such as killer-cell immunoglobulin-like receptors (KIRs), particularly in underrepresented African populations.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"17 ","pages":"1982540"},"PeriodicalIF":3.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13690946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149266028","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 spectrum of tumorigenesis in an <i>IDH1</i>-mosaic patient with Ollier disease, acute myeloid leukaemia, and parathyroid adenoma.","authors":"Victoria Lopez Delhoulle, Adrien De Voeght, Rafael Fernandez Carazo, Iulia Nechifor-Potorac, Edith Sepulchre, Evelyne Willems, Patrick Pétrossians, Benjamin Koopmansch, Elisa Docampo, Vincent Bours, Saskia Bulk, Frédéric Lambert","doi":"10.3389/fgene.2026.1889201","DOIUrl":"10.3389/fgene.2026.1889201","url":null,"abstract":"<p><p>We report the case of an 18-year-old woman with a childhood diagnosis of Ollier disease-a rare skeletal dysplasia marked by multiple enchondromas and a high risk of malignant transformation into chondrosarcoma. She later developed acute myeloid leukaemia (AML) and a parathyroid adenoma, where the same pathogenic <i>IDH1</i> variant [c.394C>T (p.Arg132Cys)] was identified in an enchondroma, AML cells, and the parathyroid adenoma. This gain-of-function variant leads to aberrant production of D-2-hydroxyglutarate, which promotes tumorigenesis through mechanisms such as DNA hypermethylation and impaired cellular differentiation. The presence of this variant in neoplasms arising from both mesodermal tissues (bone marrow, enchondromas) and a predominantly endodermal tissue (parathyroid), with the variant allele frequencies ranging from 37% to 44%, suggests an early postzygotic mosaic event. This case illustrates the broad oncogenic potential of <i>IDH1</i> mosaicism and underscores the importance of long-term multidisciplinary surveillance. In particular, the risks of chondrosarcoma and glioma that were previously reported in association with <i>IDH1-</i>related Ollier disease support the need for regular surveillance of enchondromas and brain imaging in affected individuals. This case represents the third reported incidence of Ollier disease associated with AML and the first reported incident demonstrating the same <i>IDH1</i> (p.Arg132Cys) variant across enchondroma, AML, and parathyroid adenoma, further supporting a broader tumour spectrum associated with <i>IDH1</i> mosaicism.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"17 ","pages":"1889201"},"PeriodicalIF":3.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13690521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149244250","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":"Performance of non-invasive prenatal screening for 15q11q13 copy number variations in a cohort of 90,693 pregnancies.","authors":"Diyu Chen, Liang Hu, Hongyan Niu, Zhenming Li, Shuxian Zeng, Xiaoyi Cong, Pingnan Sun, Weiqiang Liu","doi":"10.3389/fgene.2026.1937108","DOIUrl":"10.3389/fgene.2026.1937108","url":null,"abstract":"<p><strong>Background: </strong>Deletions and duplications within the 15q11q13 chromosomal region are associated with Prader-Willi syndrome, Angelman syndrome, and 15q11q13 duplication syndrome. However, prenatal ultrasound findings were unremarkable in the majority of affected fetuses. The aim of this study was to evaluate the efficacy of non-invasive prenatal screening (NIPS) in identifying these syndromes in 90,693 pregnancies within the general population.</p><p><strong>Methods: </strong>We retrospectively analyzed 90,693 pregnant women who underwent NIPS at Longgang Maternal and Child Health Hospital in Shenzhen from November 2022 to January 2026. For high-risk 15q11q13 copy number variations (CNVs) identified, we performed chromosomal microarray analysis (CMA) on amniotic fluid, followed by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) or further CMA to determine the CNVs' genetic origin, with subsequent follow-up.</p><p><strong>Results: </strong>NIPS screening identified 4 high-risk cases for 15q11q13 deletion and 7 for duplication. Among the deletion cases, 3 were confirmed by CMA to have a 5-6 Mb deletion (2 maternal, 1 unverified), while 1 declined further testing. For duplication, 6 underwent amniocentesis, with CMA confirming 5 cases (2 maternal, 2 paternal, 1 unverified), 1 normal result, and 1 declined further testing. Of the 8 true-positive cases, 7 had normal ultrasounds, but 1 fetus with duplication exhibited growth retardation. Pregnancy outcomes included 6 terminations, one delivery with paternal duplication showing mild language delay at nearly 2 years, and another with maternal duplication lost to follow-up.</p><p><strong>Conclusion: </strong>NIPS can effectively detect CNVs at the 15q11q13 locus with a high positive predictive value, but its sensitivity, specificity, negative predictive value, and false-negative rate could not be determined in this study due to the lack of confirmatory testing in low-risk cases. Invasive prenatal diagnosis remains essential for validation.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"17 ","pages":"1937108"},"PeriodicalIF":3.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13690515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149244236","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":"Artificial intelligence - driven toxicogenomics for predictive environmental and pharmaceutical safety.","authors":"Mohammed Monirul Islam, Sibghatullah Muhammad Ali Sangi, Girish Meravanige, Sreeharsha Nagaraja, Muhammad Shahzad Chohan, Md Khalid Anwer, Ashesh Gurung","doi":"10.3389/fgene.2026.1858338","DOIUrl":"https://doi.org/10.3389/fgene.2026.1858338","url":null,"abstract":"<p><p>Toxicogenomics integrates high-throughput genomic technologies with toxicology to evaluate molecular responses to chemical and pharmaceutical exposures. The increasing volume and complexity of multi-omics data necessitate advanced computational approaches capable of extracting meaningful and predictive insights. In this context, artificial intelligence (AI) and machine learning (ML) techniques-including support vector machines, random forests, and deep learning architectures-are increasingly employed for early toxicity prediction and risk assessment, with reported improvements in predictive accuracy and sensitivity relative to conventional toxicological approaches. This paper explores the role of AI-driven toxicogenomics in enhancing predictive environmental and pharmaceutical safety. It highlights the application of ML-based and data-driven models for the integrative analysis of transcriptomic, proteomic, and metabolomic datasets to identify toxicity-associated biomarkers, elucidate mechanisms of action, and predict adverse drug and environmental effects prior to clinical manifestation. Notably, AI-driven models have demonstrated significant improvements in prediction accuracy, sensitivity, and scalability compared to traditional toxicological approaches, reducing reliance on animal testing and accelerating decision-making processes. Furthermore, the paper discusses the significance of AI-based toxicogenomics in drug development, environmental contaminant screening, and regulatory toxicology, while addressing key challenges such as data heterogeneity, model interpretability, and regulatory acceptance. The convergence of computer science and toxicogenomics represents a robust framework for next-generation predictive toxicology, facilitating safer pharmaceutical development, more precise environmental risk assessment, and evidence-based public health and regulatory decision-making.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"17 ","pages":"1858338"},"PeriodicalIF":3.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149266302","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":"High-resolution characterization of classical and non-classical HLA diversity reveals important admixture in Brazilian indigenous.","authors":"Newton De Freitas Centurião, Lidia Cardoso Francisco, Manuel Mindlin Lafer, Roberta Sitnik, João Renato Rebello Pinho, Giselle Lima Groetares, Elena Outon Alonso, Gabriella Camerini Maciel, Margareth Afonso Torres","doi":"10.3389/fgene.2026.1948784","DOIUrl":"https://doi.org/10.3389/fgene.2026.1948784","url":null,"abstract":"<p><p>Understanding linkage disequilibrium (LD) patterns involving both classical and non-classical HLA genes across diverse ethnic backgrounds provides valuable insights into genomic block inheritance, ancestry inference in admixed populations, and the genetic architecture of immune-mediated diseases. We performed high-resolution typing of classical and non-classical HLA genes using next-generation sequencing in 80 Brazilian Indigenous from 24 families belonging to 24 distinct geographical indigenous communities. Gene copy number analysis was conducted in hemizygous and homozygous samples to confirm zygosity. Allelic and haplotypic frequencies, as well as Hardy-Weinberg equilibrium, were assessed in 50 unrelated individuals, while haplotypes were manually inferred through familial segregation analysis in the remaining families. Extensive allelic and haplotypic diversity was observed, with limited sharing across families and several haplotypes not previously described in the Brazilian population. In addition, haplotypes commonly reported in other ethnic groups were identified, likely reflecting the high degree of genetic admixture in Brazil. These findings contribute to the inclusion of Brazilian Indigenous populations in high-resolution immunogenetic studies and may have implications for ancestry inference, disease association analyses, and donor selection strategies in transplantation.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"17 ","pages":"1948784"},"PeriodicalIF":3.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149266259","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":"Correction: Tissue-specific aging-a new paradigm based on transcriptional insights from select model systems and humans.","authors":"Stewart Frankel, Blanka Rogina","doi":"10.3389/fgene.2026.2008131","DOIUrl":"https://doi.org/10.3389/fgene.2026.2008131","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fgene.2026.1925373.].</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"17 ","pages":"2008131"},"PeriodicalIF":3.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149266030","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":"Duplication of the <i>SOX3</i> gene in an <i>SRY</i>-negative boy with a 46,XX karyotype: a case report and a review of the literature.","authors":"Júlia Martinková, Hana Řezáčová, Alena Šantavá, Jana Drábová, Miroslav Štolfa, Radek Vodička, Jiřina Zapletalová, Miroslava Balaščaková, Anna Křepelová","doi":"10.3389/fgene.2026.1861766","DOIUrl":"10.3389/fgene.2026.1861766","url":null,"abstract":"<p><p>46,XX testicular disorder of sex development (DSD), also known as XX male syndrome, is a rare condition where an individual with a 46,XX karyotype develops a male phenotype. In 90% of cases, the syndrome results from the translocation of the <i>SRY</i> gene to the X chromosome or an autosome. The remaining 10% of individuals lack the <i>SRY</i> gene. We report a case of an <i>SRY-</i>negative 3-year-old boy with a 46,XX karyotype exhibiting normal male external genitalia. Array CGH analysis revealed a 723-kb duplication of the Xq27.1q27.2 region, encompassing the <i>SOX3</i> gene. The duplication was tandem. An imbalance in X chromosome methylation was observed, with a ratio of 4.5:1. The patient's mother and grandmother, both with a 46,XX karyotype, were asymptomatic carriers of this duplication. To date, <i>SOX3</i> duplication has been documented in 12 <i>SRY-</i>negative male patients and one female patient; eleven of these individuals exhibited various disorders of genital development. In contrast, only two previously reported patients displayed normal male genitalia, although associated with infertility. This case, the first reported in the Czech Republic, further supports the hypothesis that <i>SOX3</i> overexpression during gonadal development, accompanied by imbalanced X-chromosome inactivation, may induce testis formation, thereby compensating for the absence of the <i>SRY</i> gene in <i>SRY</i>-negative 46,XX male patients.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"17 ","pages":"1861766"},"PeriodicalIF":3.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13683180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149238144","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":"Editorial: Insights in computational genomics: 2025.","authors":"Yizhuo Yang, Zhibin Lv, Rosalba Giugno, Quan Zou","doi":"10.3389/fgene.2026.1995803","DOIUrl":"https://doi.org/10.3389/fgene.2026.1995803","url":null,"abstract":"","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"17 ","pages":"1995803"},"PeriodicalIF":3.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13683061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149238130","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":"Authorship responsibilities of scientists who use AI research agents.","authors":"David B Resnik, Mohammad Hosseini, Robert T Pennock","doi":"10.3389/fgene.2026.1954843","DOIUrl":"10.3389/fgene.2026.1954843","url":null,"abstract":"<p><p>The advent of artificial intelligence (AI) tools capable of performing research independently, which we call AI research agents (AIRAs) is likely to significantly impact how science is planned, performed, reviewed, evaluated, and communicated. However, the expected gains in efficiency and productivity from the deployment of AIRAs should not undermine science's epistemic and ethical values, such as accountability, transparency, reproducibility, and rigor. In this paper, we revisit the AI authorship debate in light of the reported capabilities of AIRAs and argue that these tools do not qualify for authorship because they cannot be held morally responsible for their contributions. We also reject the use of the term \"scientist\" to refer to these tools and argue that human scientists who use AIRAs have three key authorship responsibilities: (1) to carefully oversee and manage AIRAs; (2) to accurately and appropriately disclose AIRAs' contribution to research; and (3) to be accountable for research involving AIRAs by addressing questions and concerns raised by the scientific community and the public. Finally, we consider some related researcher responsibilities that are topics for future research, including the obligation to monitor, audit, and evaluate the performance of AIRAs and the obligation to address the social, economic, legal, and environmental implications of using AIRAs.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"17 ","pages":"1954843"},"PeriodicalIF":3.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13683075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149238199","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}