Genes最新文献

{"title":"Investigating the Sexual Dimorphism of Waist-to-Hip Ratio and Its Associations with Complex Traits.","authors":"Haochang Li, Shirong Hui, Xuehong Cai, Ran He, Meijie Yu, Yihao Li, Rongbin Yu, Peng Huang","doi":"10.3390/genes16060711","DOIUrl":"10.3390/genes16060711","url":null,"abstract":"<p><p><b>Background:</b> Obesity significantly impacts disease burden, with waist-to-hip ratio (WHR) as a key obesity indicator, but the genetic and biological pathways underlying WHR, particularly its sex-specific differences, remain poorly understood. <b>Methods:</b> This study explored WHR's sexual dimorphism and its links to complex traits using cross-sectional surveys and genetic data from Giant and UK Biobank (UKB). We analyzed WHR heritability, performed tissue-specific transcriptome-wide association studies (TWAS) using FUSION, and conducted genetic correlation analyses with linkage disequilibrium score regression (LDSC) and Local Analysis of [co]Variant Association (LAVA). Polygenic scores (PGS) for WHR were constructed using the clumping and thresholding method (CT), and associations with complex traits were assessed via logistic or linear models. <b>Results:</b> The genetic analysis showed sex-specific heritability for WHR, with TWAS identifying female-specific (e.g., <i>CCDC92</i>) and male-specific (e.g., <i>UQCC1</i>) genes. Global genetic correlation analysis revealed sex-specific associations between WHR and 23 traits, while local analysis identified eight sex-specific loci across five diseases. Regression analysis highlighted sex-specific associations for 70 traits with WHR and 45 traits with WHR PGS, with stronger effects in females. Predictive models also performed better in females. <b>Conclusions:</b> This study underscores WHR's sexual dimorphism and its distinct associations with complex traits, offering insights into sex-specific biological differences, health management, and clinical advancements.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12193181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144495928","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":"Incidence of Homozygous <i>SMN2</i> Deletion in Japan: Cross-Reactivity of <i>SMN2</i> Primers with <i>SMN1</i> Sequence Causes False Negatives in Real-Time PCR Screening.","authors":"Makoto Sakima, Yoshihiro Bouike, Shin-Ichi Wada, Masami Nakamae, Yoriko Noguchi, Ryosuke Bo, Hiroyuki Awano, Jumpei Oba, Hisahide Nishio","doi":"10.3390/genes16060712","DOIUrl":"10.3390/genes16060712","url":null,"abstract":"<p><p><b>Background</b>: <i>SMN1</i> and <i>SMN2</i> are causative and modifier genes, respectively, for spinal muscular atrophy (SMA). The incidence of <i>SMN1</i> homozygous deletion in Japan is 1 in 20,000. However, the incidence of <i>SMN2</i> homozygous deletion in Japan remains unknown. <b>Methods</b>: To clarify the incidence of homozygous <i>SMN2</i> deletion in Japan, real-time polymerase chain reaction (PCR) was performed on dried blood spot (DBS) samples collected from newborns nationwide. Samples with positive or ambiguous results were retested using PCR-restriction fragment length polymorphism (PCR-RFLP) and nucleotide sequence analysis. <b>Results</b>: Of the 1000 DBS samples that were screened using real-time PCR, 51 were positive. Retesting using PCR-RFLP analysis identified 10 false results: six false positives and four false negatives. Therefore, there were 49 true positives among the 1000 samples. Notably, nucleotide sequence analysis revealed that the false negatives were caused by the cross-reactivity of <i>SMN2</i> primers with <i>SMN1</i> sequences. <b>Conclusions</b>: The incidence of homozygous <i>SMN2</i> deletion in Japan is approximately 1 in 20 people. This incidence is much higher than that of homozygous <i>SMN1</i> deletion and may reflect the vulnerability of the <i>SMN2</i> region. Importantly, the results of the present study suggest that false negatives in the screening process were caused by cross-reactivity with non-target gene sequences.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12193581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144495913","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 Anomaly Detection with Functional Data Analysis.","authors":"Ria Kanjilal, Andre Luiz Campelo Dos Santos, Sandipan Paul Arnab, Michael DeGiorgio, Raquel Assis","doi":"10.3390/genes16060710","DOIUrl":"10.3390/genes16060710","url":null,"abstract":"<p><p><b>Background:</b> Genetic variation provides a foundation for understanding evolution. With the rise of artificial intelligence, machine learning has emerged as a powerful tool for identifying genomic footprints of evolutionary processes through simulation-based predictive modeling. However, existing approaches require prior knowledge of the factors shaping genetic variation, whereas uncovering anomalous genomic regions regardless of their causes remains an equally important and complementary endeavor. <b>Methods:</b> To address this problem, we introduce ANDES (ANomaly DEtection using Summary statistics), a suite of algorithms that apply statistical techniques to extract features for unsupervised anomaly detection. A key innovation of ANDES is its ability to account for autocovariation due to linkage disequilibrium by fitting curves to contiguous windows and computing their first and second derivatives, thereby capturing the \"velocity\" and \"acceleration\" of genetic variation. These features are then used to train models that flag biologically significant or artifactual regions. <b>Results:</b> Application to human genomic data demonstrates that ANDES successfully detects anomalous regions that colocalize with genes under positive or balancing selection. Moreover, these analyses reveal a non-uniform distribution of anomalies, which are enriched in specific autosomes, intergenic regions, introns, and regions with low GC content, repetitive sequences, and poor mappability. <b>Conclusions:</b> ANDES thus offers a novel, model-agnostic framework for uncovering anomalous genomic regions in both model and non-model organisms.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12192579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144495861","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":"Exploring Runs of Homozygosity and Heterozygosity in Sheep Breeds Maintained in Poland.","authors":"Tomasz Szmatola, Katarzyna Ropka-Molik, Igor Jasielczuk, Aldona Kawęcka, Artur Gurgul","doi":"10.3390/genes16060709","DOIUrl":"10.3390/genes16060709","url":null,"abstract":"<p><p><b>Objectives</b>: The study investigates runs of homozygosity (ROH) and heterozygosity (ROHet), and their patterns in nine sheep breeds (772 animals in total) maintained in Poland (native and conserved), corresponding to their genetic diversity, inbreeding levels, and selection signatures. <b>Methods</b>: Genotypes were obtained using the Illumina OvineSNP50 BeadChip and quality-filtered SNPs were used to detect ROH and ROHet segments with the detectRUNS R package, following stringent parameters for segment length, SNP density, and genotype quality. <b>Results</b>: Significant variation in ROH characteristics was observed across breeds. Short ROH segments were predominant in all breeds, indicating historical inbreeding events. In contrast, longer ROH segments signified recent inbreeding, particularly in Swiniarka (SW) and Polish Merino of Colored Variety (MPC). The ROH-based genomic inbreeding coefficient (F_ROH) varied across breeds, with SW exhibiting the highest levels, suggesting reduced genetic diversity. ROHet analysis revealed that Uhruska (UHR) had the highest heterozygous segments span, while Black-headed (BH) sheep exhibited the lowest ROHet extent. ROH islands identified across breeds revealed regions under selection, associated with traits such as reproductive performance, wool quality, and body condition. Genes located within these islands (e.g., <i>U6</i>, <i>SPP1</i>, <i>ABCG2</i>) were linked to economically significant traits including milk production, growth, and carcass quality. <b>Conclusions</b>: The presented results highlight the genetic adaptations shaped by selection pressures, while also providing insights into the genetic architecture of sheep breeds maintained in Poland.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12192788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144495784","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":"Half the Chromosome It Used to Be: Identifying Cancer Treatments Targeting Aneuploid Losses.","authors":"Andrew O Disharoon, Joe R Delaney","doi":"10.3390/genes16060708","DOIUrl":"10.3390/genes16060708","url":null,"abstract":"<p><strong>Background/objectives: </strong>Aneuploidy is near-ubiquitous in cancer and can decrease chemotherapy efficacy while also sensitizing cells to other drugs.</p><p><strong>Methods: </strong>To systematically identify treatment strategies that target aneuploid cancers, data were integrated from The Cancer Genome Atlas (TCGA; 10,967 samples, 16,948 aneuploidy events) and the Broad Institute's Profiling Relative Inhibition Simultaneously in Mixtures (PRISM) screen of 578 cancer cell lines and 4518 compounds.</p><p><strong>Results: </strong>Our analyses uncovered 37,720 significant positive and negative associations linking specific aneuploidies and treatments with patient prognosis or cell viability. Within TCGA data, 22 treatments correlated with improved 5-year survival for specific aneuploid cancers, whereas 46 were linked to worse outcomes. A complementary analysis of PRISM identified 17,946 compound-aneuploidy associations and 16,189 mechanism of action (MOA)-aneuploidy associations. Pathway-altering compounds that selectively reduce viability in cells with aneuploidy profiles were discovered, including an unexpectedly prominent number of glucocorticoid receptor agonists.</p><p><strong>Conclusions: </strong>This integrated dataset provides a resource for designing therapeutic decision hypotheses, identifying drug-repurposing opportunities, and informing future studies aimed at targeting aneuploidy-induced vulnerabilities in cancer.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12192454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144495904","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":"<i>MPDZ</i> Pathogenic Variants Cause Obstructive Ventriculomegaly Related to Diencephalosynapsis and Third Ventricle Atresia.","authors":"Sara Cabet, Jean-François Ghersi-Egea, Suonavy Khung-Savatovsky, Fabien Guimiot, Audrey Putoux, Isabelle Sabatier, Carla Fernandez, Laure Raymond, Jérémie Mortreux, Hélène Laurichesse Delmas, Fabrice Eric Cuillier, Fabien Ho, Gaetan Lesca, Jean-Luc Alessandri, Laurent Guibaud","doi":"10.3390/genes16060707","DOIUrl":"10.3390/genes16060707","url":null,"abstract":"<p><strong>Objective: </strong>Ventriculomegaly is the main prenatal imaging feature for diagnosing fetal central nervous system anomalies in humans. Many ventriculomegalies can be related to genetic causes, regardless of their imaging presentations. Among these, <i>MPDZ</i> variants have been reported to cause severe ventriculomegaly inherited in an autosomal recessive manner (OMIM#615219). Several hypotheses have been put forward linking <i>MPDZ</i> variants to ventriculomegaly, but the precise underlying mechanisms, in particular whether its origin is obstructive or non-obstructive, are yet to be elucidated.</p><p><strong>Methods: </strong>To address this question, we retrospectively analyzed pre- and postnatal neuro-imaging and neuropathological data for cases of ventriculomegaly in which <i>MPDZ</i> variants were found through exome or genome sequencing. We performed anti-MPDZ immunostaining on fetal brain samples.</p><p><strong>Results: </strong>We analyzed six cases (four fetuses and two children) of ventriculomegaly of variable severities with <i>MPDZ</i> variants. The precise analysis of brain MRI data, corroborated by fetopathological examinations, demonstrated an obstructive pattern of ventriculomegaly upstream from partial fusion of the thalami, also called diencephalosynapsis, with partial atresia of the third ventricle, which could extend to Sylvius's aqueduct.</p><p><strong>Conclusions: </strong>The morphological analysis using targeted brain magnetic resonance imaging (MRI) and neuropathological data allowed us to unravel the underlying mechanisms of congenital ventriculomegaly related to <i>MDPZ</i> variants.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12192413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144495867","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":"Expansion of the Genotypic and Phenotypic Spectrum of <i>TCTN3</i>-Related Joubert Syndrome.","authors":"Mariangela Lo Giudice, Eugenia Borgione, Marika Giuliano, Sandro Santa Paola, Francesco Domenico Di Blasi, Rosa Pettinato, Corrado Romano, Carmela Scuderi","doi":"10.3390/genes16060706","DOIUrl":"10.3390/genes16060706","url":null,"abstract":"<p><strong>Background/objectives: </strong>Joubert syndrome (JS, MIM 213300) is a rare genetic condition characterized by respiratory control disturbances, abnormal eye movements, ataxia, cognitive impairment, and the notable agenesis of the cerebellar vermis. The molar tooth sign visible in magnetic resonance imaging of the brain serves as a diagnostic tool for JS. Variants in the <i>TCTN3</i> gene can lead to the development of several diseases, including JS type 18, Orofaciodigital syndrome IV, and Meckel-Gruber syndrome.</p><p><strong>Methods: </strong>We performed whole-exome sequencing (WES) in a 49-year-old woman with JS characterized by severe intellectual disability, ataxic gait, agenesis of the cerebellar vermis leading to the molar tooth sign, dystonic movements, strabismus, and nystagmus. Moreover, the patient also showed a thickened corpus callosum.</p><p><strong>Results: </strong>Molecular analysis through WES revealed the heterozygous variants c.182dup (p.G62Wfs*18) and c.1452+4del in the <i>TCTN3</i> gene, expanding our understanding of the genetic diversity and potential phenotypic implications associated with <i>TCTN3</i> variations.</p><p><strong>Conclusions: </strong>To our knowledge, this is the first patient with JS and a thickened corpus callosum. Moreover, a thickened corpus callosum has never been identified in patients with pathogenic variants of the <i>TCTN3</i> gene.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12193267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144495783","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":"The Integrative Taxonomy and Mitochondrial Genome Evolution of Freshwater Planarians (Platyhelminthes: Tricladida): The Discovery of a New Clade in Southern China.","authors":"Yimeng Yang, Zhizhuo Huang, Xiaowen Fang, Pinyi Li, Yexin Li, Xiuying Hou, Yongjun Li, Hengwen Yang, Chunxia Jing, Zhinan Yin, Guang Yang","doi":"10.3390/genes16060704","DOIUrl":"10.3390/genes16060704","url":null,"abstract":"<p><strong>Background: </strong>The genus <i>Dugesia</i> (Platyhelminthes: Tricladida) includes a large diversity of free-living freshwater flatworms and is important for studies on regeneration and evolution. This study aims to describe a newly discovered asexual planarian species from southern China and explore its genetic characteristics and regenerative abilities.</p><p><strong>Methods: </strong>An integrative taxonomic analysis was conducted using morphology, karyology, histology, molecular phylogeny (18S, 28S, COI, mitogenome), and genome size estimation via flow cytometry. Regeneration was assessed by standardized amputations, and long-term asexual propagation was observed under laboratory conditions for three years.</p><p><strong>Results: </strong>Phylogenetic analyses using nuclear (18S, 28S rDNA) and mitochondrial (COI, mitogenome) markers confirmed that <i>Dugesia cantonensis</i> Guang Yang & Zhinan Yin, sp. nov. forms a distinct clade within <i>Dugesia</i>. Its 18,125 bp mitogenome contains 36 genes but lacks atp8. <i>D. cantonensis</i> displays a distinctive morphology, notably a pharynx located near the head. All body fragments regenerated into complete individuals within nine days. Remarkably, one individual produced ~10⁵ clonal descendants over three years via repeated amputation, maintaining stable regenerative ability and growth across generations. Karyological analysis revealed a diploid karyotype (2<i>n</i> = 16) consisting of eight chromosome pairs. The nuclear genome size was estimated at approximately 2.5 Gb using <i>Danio rerio</i> as an internal standard. Histological examination showed no detectable reproductive organs, confirming the species as an exclusively asexual lineage.</p><p><strong>Conclusions: </strong><i>D. cantonensis</i> represents a new planarian strain with stable propagation and regeneration. These features make it a valuable resource for regenerative biology and comparative genomic studies.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12192195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144495919","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":"Human CD36: Gene Regulation, Protein Function, and Its Role in Atherosclerosis Pathogenesis.","authors":"Monika Rac","doi":"10.3390/genes16060705","DOIUrl":"10.3390/genes16060705","url":null,"abstract":"<p><p>Human CD36 plays an important role in ligand binding, signalling, cell adhesion, and the regulation of angiogenesis. As a scavenging receptor, it is responsible for clearing long-chain fatty acids (LCFAs) and removing approximately 50% of oxidised low-density lipoprotein (ox-LDL) from plasma. The <i>CD36</i> gene is alternatively spliced. It has several alternative promoters and first exons. The alternative transcripts are expressed in multiple tissues, and their expression patterns are highly variable. The molecular mechanisms that regulate <i>CD36</i> gene expression are complex and reflect its multifunctional role in different tissues. CD36 activity has been linked to several metabolic processes, such as inflammation, angiogenesis, phagocytosis, and energy homeostasis. CD36 plays a key role in regulating vascular and cardiovascular health and in the pathogenesis of atherosclerosis. <i>CD36</i> gene mutations in the Caucasian population are rare. Hence, it is extremely difficult to recruit a statistically significant group of CAD patients with these mutations. Nevertheless, this population is largely at risk of cardiovascular disease. Atherosclerosis is a multifactorial disease, but the role of the CD36 receptor in the development of ox-LDL is extremely important. This review aims to introduce readers to issues related to the relationship between CD36 and CAD. The activity of this receptor should be considered when exploring treatment options for atherosclerosis-related complications.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12192553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144495906","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":"Origin and Evolution of Genes in Eukaryotes: Mechanisms, Dynamics, and Functional Implications.","authors":"Salvatore Saccone, Desiree Brancato, Francesca Bruno, Elvira Coniglio, Valentina Sturiale, Concetta Federico","doi":"10.3390/genes16060702","DOIUrl":"10.3390/genes16060702","url":null,"abstract":"<p><p>The origin and evolution of genes are central themes in evolutionary biology and genomics, shedding light on how molecular innovations shape biological complexity and adaptation. This review explores the principal mechanisms underlying gene emergence in eukaryotes, including gene duplication, de novo gene birth, horizontal gene transfer, viral gene domestication, and exon shuffling. We examine the population dynamics that govern the fixation of new genes, their functional integration, and the selective forces acting upon them-from purifying selection to adaptive innovation. Examples such as <i>NOTCH2NL</i> and <i>SRGAP2C</i>, which originated through recent segmental duplications followed by neofunctionalization, illustrate how duplicate-derived de novo genes can play a key role in human brain development. In addition, we highlight the emerging relevance of nuclear architecture in determining the evolutionary fate of new genes, offering a spatial dimension to gene innovation. We also discuss methodological approaches for detecting new genes and inferring selection, and finally, we highlight the emerging role of the human pangenome in revealing hidden gene diversity and its implications for evolutionary and biomedical research. Understanding gene innovation not only enhances our grasp of evolutionary processes but also informs clinical studies on disease susceptibility and human uniqueness.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"16 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12193501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144495956","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}