Human Genomics最新文献

{"title":"ExposoGenomics: integrating genome and exposome as jointly dynamic systems for causal discovery and precision health.","authors":"Vasilis Vasiliou, Nicholas Katsanis, Giuseppe Novelli, Juergen K V Reichardt, Bassam R Ali, Maria Gazouli, Sek Won Kong, Hongyu Zhao, Kiril Veselkov, Bhramar Mukherjee, Dimosthenis Sarigiannis","doi":"10.1186/s40246-026-01014-w","DOIUrl":"https://doi.org/10.1186/s40246-026-01014-w","url":null,"abstract":"<p><p>The past decade has witnessed an unprecedented convergence of exposomic technologies, population-scale genomics, and AI-enabled data science, creating the conditions for a new integrative discipline. Here we introduce ExposoGenomics, defined as the integrative study of how the genome and exposome, treated as jointly dynamic systems, interact across the life course to shape health and disease. ExposoGenomics moves beyond classical gene-environment interaction models by embedding high-dimensional, temporally resolved exposure data within a multi-omic and AI-enabled analytical architecture oriented toward causal discovery, mechanistic understanding, and translational application. We describe the conceptual foundations of this framework, its mechanistic architecture linking external exposures to genomic responses through physiologically based kinetic models and adverse outcome networks, and the analytical approaches, including causal machine learning, graph-based integration, and foundation models, required to realize its potential. We emphasize that computational prediction must be accompanied by rigorous empirical validation, and that findings must be grounded in biologically plausible, causally supported mechanisms. In conjunction with this Perspective, Human Genomics formally launches ExposoGenomics as a dedicated article category and invites submissions that advance this integrative agenda.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of APOC2 upstream variant rs10425530 with BMI predicted to overlap with NR2C2, GCM2 and NR2C1 binding sites.","authors":"Suzanne A Al-Bustan, Babitha G Annice, Hasan Alhaddad","doi":"10.1186/s40246-026-01015-9","DOIUrl":"https://doi.org/10.1186/s40246-026-01015-9","url":null,"abstract":"<p><strong>Background: </strong>Lipid metabolism involves multiple genes that contribute to various diseases including metabolic disorders. Although extensive research has focused on identifying large-effect variants in coding regions, few studies have examined the effects of variations in regulatory and non-coding regions. Apolipoprotein C2 (APOC2) gene plays a central role in activating lipoprotein lipase; however, the effect of upstream variants on its transcriptional regulation remains unclear. We aimed to (1) identify genetic variants in a targeted APOC2 upstream region of, (2) annotate and characterize predicted cis-regulatory elements (CREs) in-silico, (3) map identified variants to transcription factor binding sites (TFBS), and (4) evaluate the association of selected variants with dyslipidemia and body mass index (BMI).</p><p><strong>Results: </strong>Twelve variants were identified by sequencing of the APOC2 targeted region in a Kuwaiti cohort (n = 600). In-silico annotation using multiple tools identified 626 putative CRE within the targeted region which were prioritized into 48 predicted TFBS of functional relevance. Four variants (rs10425530, rs111782345, rs112698600, and rs2288912) met the criteria for association testing. A significant independent association, employing multivariate analysis, was observed between rs10425530 and BMI under a dominant model (β = 2.26; p = 0.022) among the Kuwaiti Arabs that requires further investigation in a large cohort. Motif-based analyses predicted that the rs10425530 A allele may alter the binding affinity of NR2C2, NR2C1, and GCM2 motifs by 21.10%, 23.80% and 20.40%, respectively.</p><p><strong>Conclusions: </strong>Two hypothetical models have been proposed to explain the observed association between rs10425530 and increased BMI and the predicted effect on TFBS: (1) disruption of NR2C1/NR2C2 binding sites may influence APOC2 regulation via interactions with nuclear receptors involved in energy balance and/or (2) disruption of a GCM2 binding site may act via long-range regulatory effects on parathyroid hormone pathways. These findings are exploratory and require replication in larger independent cohorts and warrants further in-vitro and in-situ investigations to elucidate definitive functional assignments in regulatory activity and chromatin accessibility. The analytical framework applied in this study could provide basis for improving the interpretation of non-coding genomic variations and groundwork for future studies combining in-silico functional predictions and experimental analysis.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding dry eye disease based on bioinformatics and in vitro experimental: the role of immune responses and natural product intervention.","authors":"Xi Long, Guicheng Liu, Pei Liu, Pengfei Jiang, Jun Peng, Qinghua Peng","doi":"10.1186/s40246-026-00992-1","DOIUrl":"https://doi.org/10.1186/s40246-026-00992-1","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Dry eye disease (DED), a prevalent ocular condition, has seen rising incidence rates. Aberrant inflammation and immune dysregulation are key pathogenic factors in DED. However, the underlying mechanisms linking autoimmunity to DED therapy remain incompletely understood. Herbal medicine's potential in treating DED warrants further exploration due to rendering monotherapy insufficient for clinical needs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;DED-related datasets and genes were initially identified from the GEO database and other public repositories. After retrieving the data, differential gene expression analysis and functional enrichment analysis were performed. Subsequently, a protein-protein interaction network was constructed to identify core modules and hub genes. To enhance the reliability and diagnostic value of these findings, the hub genes were further validated using independent external datasets and refined through machine learning algorithms (LASSO and SVM-RFE) to extract characteristic genes. These characteristic genes were then used for reverse prediction of potential Traditional Chinese Medicine natural products, leading to the construction of a gene-natural products network. Following this, molecular docking was employed to screen for promising natural products based on binding affinity. In parallel, immune cell infiltration was estimated using CIBERSORTx, and single-cell RNA sequencing data were analyzed to elucidate cell-type-specific expression patterns of the characteristic genes. Finally, the therapeutic potential of the top-predicted natural product was validated using an in vitro cellular model of DED.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;GSE44101 was selected as the base dataset. Differential gene analysis identified 1089 differential genes and 3504 DED-related genes from five databases, with 235 overlapping genes. Enrichment analysis linked DED to Cytokine-Cytokine receptor interaction, PI3K-Akt, IL-17, and JAK-STAT signaling pathways. The PPI network yielded 20 hub genes, validated and refined using other GEO datasets and machine learning, resulting in 10 characteristic genes: CDK1, CCNA2, CXCL13, CCR1, FEN1, CCR7, SELL, RAD51, CXCL1, and KIF11. Genistein was identified as the key TCM natural product. Molecular docking revealed stable interactions between Genistein and CDK1, IL-1β, CDC20, and CCNA2, with CDC20 showing the highest stability. CIBERSORT analysis demonstrated associations between characteristic genes and specific immune cell infiltration in DED. Single-cell RNA sequencing localized their expression to key corneal cell types, with IL-1β predominantly expressed in macrophages. Cell experiments confirmed that Genistein at a concentration of 12.5 μmol/L could protect human corneal epithelial cells from NaCl-induced hyperosmotic damage and TNF-α-induced immune injury, reducing the cell detachment rate and decreasing the area of cell death loss. Genistein downregulated the expression of CDK1, IL","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic reconstruction of the Pakistani Roma reveals dual South Asian ancestry, medieval bottlenecks, and the early dispersal routes of the Romani people.","authors":"Atif Adnan, Hao Dong Chen, Allah Rakha, Muhammad Ilyas, Chuan-Chao Wang","doi":"10.1186/s40246-026-00965-4","DOIUrl":"https://doi.org/10.1186/s40246-026-00965-4","url":null,"abstract":"<p><p>The Roma people represent one of the largest and most historically enigmatic diasporas in Eurasia, illuminating human migration patterns and cultural resilience across continents. Despite extensive research on European Roma as the diaspora endpoint, the genetic legacy of their putative South Asian source populations remains critically underexplored, leaving fundamental gaps in understanding the pre-diaspora demographic structure and early dispersal dynamics. This study uniquely positions Pakistani Roma as a potential ancestral reservoir, offering a rare window into the pre-migration phase distinct from derived European Roma populations shaped by centuries of post-dispersal admixture. We analyze 82 Pakistani Roma from Punjab using high-resolution genome-wide SNP data and comprehensive mitochondrial haplogroup profiling to reconstruct their genetic origins, population structure, and historical trajectory. Analyses reveal a dual ancestry profile comprising 50-82% Indus Valley related, 20-30% Onge related, and up to 26% Steppe derived components, with three distinct subgroups exhibiting varying affinities along a South Asian to Central Western Eurasian continuum reflecting jati-like endogamy. A severe demographic bottleneck ~800 years ago coincides with medieval socio-political upheavals, while major Eurasian admixture is dated to ~660 years ago. Mitochondrial haplogroups H (45.12%) and M (26.83%) underscore dual maternal influences from West and South Eurasia. Pakistani Roma retain substantially higher South Asian ancestry than their European counterparts, establishing them as a genetically distinct population preserving the ancestral pre-diaspora state. These findings redefine the Romani origin narrative and underscore the critical value of understudied South Asian minorities in reconstructing complex human migration pathways and diaspora formation mechanisms.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148420914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferroptosis-related TFRC: a potential therapeutic target in sepsis and regulatory effect of γ-Tocotrienol.","authors":"Yandong Yao, Gege Ke, Yuanxin Wu, Haili Li, Yingchun Hu, Muhu Chen","doi":"10.1186/s40246-026-01003-z","DOIUrl":"https://doi.org/10.1186/s40246-026-01003-z","url":null,"abstract":"<p><strong>Background: </strong>Ferroptosis, an iron-dependent regulated cell death, plays a critical role in the pathophysiology of sepsis. This study aimed to identify core targets and therapeutic agents related to ferroptosis in sepsis.</p><p><strong>Methods: </strong>Differential analysis of peripheral blood RNA-sequencing data from 19 patients with sepsis and 10 healthy controls was performed. Ferroptosis-related hub genes were identified via a PPI network and validated by Mendelian randomization, protein cohort studies, and survival/meta-analyses. Single-cell sequencing localized core genes, and in vitro/in vivo experiments explored targeted drugs.</p><p><strong>Results: </strong>High TFRC expression correlated with poor sepsis prognosis. TFRC was predominantly expressed in monocytes and B cells, with more monocytes in non-survivors. γ‑Tocotrienol (γ‑T3) treatment was associated with reduced TFRC expression, lower ROS and IL‑1β levels, and improved survival in septic zebrafish and mice.</p><p><strong>Conclusion: </strong>TFRC is a potential therapeutic target for ferroptosis in sepsis. γ‑T3 alleviates LPS-induced TFRC upregulation and improves survival in septic mice, suggesting its potential as a therapeutic agent.</p><p><strong>Study registration: </strong>ChiCTR1900021261 (Chinese Clinical Trial Registry), registered February 4, 2019.</p><p><strong>Type of study: </strong>retrospective observational study using archived biological samples.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148411612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ancestry specific polygenic risk score, dietary patterns, physical activity and incident type 2 diabetes.","authors":"Dale S Hardy, Jane T Garvin, Tennille S Leak-Johnson, Tesfaye B Mersha","doi":"10.1186/s40246-025-00900-z","DOIUrl":"10.1186/s40246-025-00900-z","url":null,"abstract":"<p><strong>Background: </strong>It is unknown whether the impact of lifestyle could mitigate the genetically driven high-risk polygenic risk score (PRS) in different ancestries.</p><p><strong>Objectives: </strong>We determined associations and interactions between high-risk PRS, dietary patterns, physical activity, and metabolic burden and their impact on incident type 2 diabetes mellitus (T2DM) in European Americans and African Americans. A secondary aim determined ancestry-specific PRS-mapped genes associated molecular pathways.</p><p><strong>Methods: </strong>Our longitudinal study (1976-2015) utilized de-identified data for European American (n = 8,283) and African American (n = 1,205) from 7-National Heart, Lung, and Blood Institute Candidate Gene Association Resource studies from the Database of Genotypes and Phenotypes. We assessed results using biased-corrected odds ratios (OR) and 95% confidence intervals (CI).</p><p><strong>Results: </strong>African Americans had a higher magnitude of incident T2DM risk for the high-risk PRS alone (OR = 1.61; 95% CI:1.22-2.12) than European Americans (OR = 1.24; 95% CI:1.06-1.45) in highest tertile compared to lowest tertile. We observed protective risks from incident T2DM with the Dietary Approaches to Stop High Blood Pressure (DASH) and Mediterranean diets (p < 0.025). However, entangling effects from the high-quality DASH/Mediterranean diets with the low-quality Southern diet and the high-risk PRS further increased T2DM risks (p < 0.025). The PRS-diet-physical activity associations had 9% protective T2DM risk for Mediterranean diet in African Americans and at least 5% for European Americans (p < 0.025). Interactions revealed the second tertile DASH and highest tertile Mediterranean diets in high-risk PRS-high metabolic burden, attenuated incident T2DM risk. Gene enrichment molecular pathways common to ancestries included neurogenerative diseases, lipid metabolism, and glucose metabolism.</p><p><strong>Conclusions: </strong>Patients in the highest PRS tertiles with high metabolic burden could be targeted for early intervention to decrease T2DM risk. The DASH and Mediterranean diets with high physical activity should be recommended by clinicians for better prevention, detrimental molecular pathway reversal, and to decrease worsening of T2DM from high metabolic burden.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"20 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13343712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148404520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutational spectrum of SLC26A4 and SLC26A5 associated with hereditary hearing loss in Moroccan families.","authors":"Assia Idyahia, Salaheddine Redouane, Fatima Ezzahra Chentoufi, Hicham Charoute, Adil El Hamouchi, Houda Benrahma, Abdelhamid Barakat","doi":"10.1186/s40246-026-01010-0","DOIUrl":"https://doi.org/10.1186/s40246-026-01010-0","url":null,"abstract":"<p><strong>Background: </strong>The solute carrier family 26 (SLC26) encodes multifunctional anion transporters that mediate the transmembrane exchange of monovalent and divalent anions. While pathogenic variants in several SLC26 genes cause inherited disorders, only SLC26A4 and SLC26A5 have been linked to hereditary hearing loss (HHL).</p><p><strong>Results: </strong>Exome sequencing performed in probands from nine unrelated Moroccan families with sensorineural hearing loss identified eight SLC26A4 variants, including previously reported and novel variants, as well as a homozygous canonical splice-site variant in SLC26A5 (c.1311 + 1G > T). Sanger sequencing confirmed co-segregation of all identified variants, and in silico prediction tools consistently supported their pathogenicity. Molecular dynamics simulations performed on three SLC26A4 missense variants (p. Ser353Ala, p. Phe555Cys, and p. Leu582Pro) indicated significant, state-dependent alteration in pendrin's structural stability, suggesting impaired conformational transitions required for efficient Cl⁻/HCO₃⁻ exchange.</p><p><strong>Conclusion: </strong>This study provides a comprehensive molecular characterization of SLC26A4- and SLC26A5-related hearing loss in Moroccan families and significantly expands the mutational landscape of hereditary hearing loss in North Africa.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148368254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"National genomic projects in Asia and Africa: a review.","authors":"Aisha Hanaya Alsuwaidi, Mira Mousa, Michael Olbrich, Nour Al Dain Marzouka, Inken Wohlers, Saleh Ibrahim, Habiba Alsafar","doi":"10.1186/s40246-026-01007-9","DOIUrl":"10.1186/s40246-026-01007-9","url":null,"abstract":"<p><p>National genome projects (NGPs) are increasingly shaping precision medicine by improving representation of population-specific genetic diversity. This review compiles findings from NGPs across Asia and Africa, regions that remain underrepresented in global genomic databases despite their extensive demographic and genetic diversity. A total of 53 studies from 24 countries were identified to understand (1) the genomic approach utilized, (2) novel findings that have emerged, and (3) strategies for improving research in these regions. The NGPs implement population-based variome databases (20 NGPs), linear reference genome assemblies (8 NGPs), and graph-based pangenome assemblies (1 NGP). Novel variants ranged between 0.28% (China) and 19.6% (Iran), whereas rare variants accounted for up to 88.9% of the detected variants in the Chinese population. Each NGP documents its country's evolutionary and migration history, which impacts disease frequency and pharmacogenomic variants. Clinically, NGPs revealed strong population stratification in disease-associated and pharmacogenomic variants. For example, the GJB2 rs72474224 hearing-loss variant ranged from 13% in Vietnam and 12% in Hong Kong to 0.0894% in Turkey, while the VKORC1 rs9923231 pharmacogenomic variant reached 89.2% in Taiwan but was 20%-25% in European-related Russian subpopulations. These findings demonstrate that clinically relevant allele frequencies, pathogenicity assessments, and drug-response markers differ substantially across ancestries. This review highlights ongoing efforts and strategies to enhance the representativeness of genomic data through NGPs in Asia and Africa. We also suggest future directions for national projects, including integrating family-based studies, multi-omic data, and standardized pipelines to accelerate discovery and support the equitable implementation of precision medicine.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148360483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of whole-exome sequencing data from nearly 10,000 Iranian individuals: identification of recessive mitochondrial disease variants and proposal of a population-specific carrier screening panel.","authors":"Mohadeseh Fathi, Parvaneh Karimzadeh, Farzad Ahmadabadi, Damoun Nashta Ali, Narjes Jafari, Raheleh Tangestani, Shadab Salehpour, Toktam Moosavian, Soudeh Ghafouri-Fard, Mohammad Miryounesi","doi":"10.1186/s40246-026-01011-z","DOIUrl":"https://doi.org/10.1186/s40246-026-01011-z","url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial diseases, often stemming from recessive nuclear gene mutations, represent a heterogeneous group of disorders with significant morbidity and mortality. Carrier screening for these conditions is population-specific, yet data on the pathogenic variant burden in the Iranian population remain limited. This study aimed to analyze whole-exome sequencing (WES) data from 9989 Iranian individuals to identify the spectrum and frequency of recessive mitochondrial disease variants and to develop a population-specific carrier screening panel.</p><p><strong>Methods: </strong>We analyzed WES data from 9989 unrelated Iranian individuals. Variants in 1,564 nuclear genes associated with mitochondrial function were filtered for rarity (minor allele frequency < 0.01 in public databases), predicted pathogenicity, and recessive inheritance patterns (homozygous or compound heterozygous). Clinically relevant variants were manually curated, and carrier frequencies for significant recessive mitochondrial conditions were calculated.</p><p><strong>Results: </strong>Our analysis identified variants across 15 groups of mitochondrial-related nuclear genes in 345 individuals recognized as carriers. Of these, 123 variants (35.6%) were classified as Pathogenic, and 154 variants (44.6%) were classified as Likely Pathogenic according to ACMG guidelines.</p><p><strong>Conclusions: </strong>This study provides the first large-scale WES-derived assessment of recessive mitochondrial disease carrier burden in the Iranian population. The high estimated carrier rate supports implementing population-specific preconception screening. The results of this study can be used for design of targeted panels of nuclear mitochondrial genes to identify at-risk couples, facilitating genetic counseling and reproductive decision-making in Iran.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148360468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Replicating lipid micelles: a feasible precursor to the origin of life and the earliest appearance of genomes.","authors":"Daniel W Nebert, Zijuan Liu, Vasilis Vasiliou","doi":"10.1186/s40246-026-01005-x","DOIUrl":"10.1186/s40246-026-01005-x","url":null,"abstract":"<p><p>The most commonly accepted scenario of early Earth includes: creation of the universe around 13.8 Ga (Giga-annus; or 10⁹ years ago); establishment of our solar system ~ 4.60 Ga; and formation of Earth ~ 4.54 Ga. The earliest life forms on our planet so far observed to have existed, are microbes that left signals of their presence in rocks ~ 3.6 Ga - suggesting that Life forms existed within the first 940 million years after Earth's formation. However, an intriguing recent publication [1] infers that the last universal common ancestor (LUCA) likely existed by 4.2 Ga, and that the inferred LUCA had a genome of at least 2.5 Mb of DNA, encoding around 2,600 proteins; this suggests that sophisticated Life might have existed within the first 340 million years after Earth was formed. The commonly accepted geological history of early Earth suggests that the turbulent Hadean Eon lasted until 4.0 Ga, with the Late Heavy Bombardment (LHB) period occurring around 4.1 to 3.8 Ga. If Earth during the Hadean exhibited a molten surface, intense volcanic activity, and constant bombardment by asteroids and comets - how were sensitive molecules (e.g., nucleic acids, proteins) able to survive? Considering the \"Lipid First\" hypothesis [2], we propose that replicating lipid micelles are feasible candidates for having populated much of Earth's deep hydrothermal vents and turbulent surface within the first 340 million years of Earth's existence. These lipid micelles could therefore have provided a plausible form of \"protective capsules\" inside which early Life's sensitive molecules were able to evolve.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148316970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}