'; ?> geneimprint : Hot off the Press http://www.geneimprint.com/site/hot-off-the-press Daily listing of the most recent articles in epigenetics and imprinting, collected from the PubMed database. en-us Sat, 16 Aug 2025 12:21:54 EDT Sat, 16 Aug 2025 12:21:54 EDT jirtle@radonc.duke.edu james001@jirtle.com Association between placental epigenetic age acceleration and early postnatal growth patterns. Patel P, Shen A, Perez C, Kennedy EM, Shankar K, Pearson KJ, Andres A, Everson TM
Sci Rep (Aug 2025)

Placental gestational age acceleration (GAA) is the difference between the actual gestational age (GA) at birth and their estimated epigenetic gestational age (EGA), which is calculated from placental DNA methylation. Understanding the role of placental GAA in postnatal growth trajectories is crucial for early identification of infants at risk of altered growth patterns and associated long-term health outcomes. The objective of this study is to investigate the association between placental GAA and longitudinal growth trajectories specifically weight, height, fat mass, and lean mass gain in early childhood. This study uses placental DNA methylation at birth to calculate epigenetic GAA and longitudinal measures of weight, height, fat mass, and lean mass to generate growth trajectory characteristics. Higher placental GAA was significantly associated with slower weight gain (95% CI [- 0.03, - 0.001]) and fat mass (95% CI [- 0.08, - 0.02]) gain, as well as reduced average fat mass (95% CI [add this]) over the follow-up period. However, no significant associations were found between GAA and height or lean mass gain. Placental GAA can give early insights into altered postnatal growth trajectories, particularly for weight and fat mass where an increase in GAA is associated with decreased weight and fatmass gain over time while we observed no effect on height and lean mass. Understanding these associations offers insights into early developmental patterns and long-term health outcomes in children, highlighting the importance of perinatal factors in shaping growth trajectories in early childhood.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenetic and genetic profiling of comorbidity patterns among substance dependence diagnoses. Pathak GA, Pietrzak RH, Lacobelle A, Overstreet C, Wendt FR, Deak JD, Friligkou E, Nunez YZ, Montalvo-Ortiz JL, Levey DF, Kranzler HR, Gelernter J, Polimanti R
Mol Psychiatry (Sep 2025)

This study investigated the genetic and epigenetic mechanisms underlying the comorbidity of five substance dependence diagnoses (SDs; alcohol, AD; cannabis, CaD; cocaine, CoD; opioid, OD; tobacco, TD). A latent class analysis (LCA) was performed on 22,668 individuals from six cohorts to identify comorbid DSM-IV SD patterns. In subsets of this sample, we tested SD-latent classes with respect to polygenic overlap of psychiatric and psychosocial traits in 7659 individuals of European descent and epigenome-wide changes in 886 individuals of African, European, and Admixed-American descents. The LCA identified four latent classes related to SD comorbidities: AD + TD, CoD + TD, AD + CoD + OD + TD (i.e., polysubstance addiction, PSU), and TD. In the epigenome-wide association analysis, SPATA4 cg02833127 was associated with CoD + TD, AD + TD, and PSU latent classes. AD + TD latent class was also associated with CpG sites located on ARID1B, NOTCH1, SERTAD4, and SIN3B, while additional epigenome-wide significant associations with CoD + TD latent class were observed in ANO6 and MOV10 genes. PSU-latent class was also associated with a differentially methylated region in LDB1. We also observed shared polygenic score (PGS) associations for PSU, AD + TD, and CoD + TD latent classes (i.e., attention-deficit hyperactivity disorder, anxiety, educational attainment, and schizophrenia PGS). In contrast, TD-latent class was exclusively associated with posttraumatic stress disorder-PGS. Other specific associations were observed for PSU-latent class (subjective wellbeing-PGS and neuroticism-PGS) and AD + TD-latent class (bipolar disorder-PGS). In conclusion, we identified shared and unique genetic and epigenetic mechanisms underlying SD comorbidity patterns. These findings highlight the importance of modeling the co-occurrence of SD diagnoses when investigating the molecular basis of addiction-related traits.]]> Wed, 31 Dec 1969 19:00:00 EST and are human placenta-specific imprinted genes associated with germline-inherited maternal DNA methylation. Daskeviciute D, Sainty B, Chappell-Maor L, Bone C, Russell S, Iglesias-Platas I, Arnaud P, Monteagudo-Sánchez A, Greenberg MVC, Chen K, Manerao-Azua A, Perez de Nanclares G, Lartey J, Monk D
Epigenetics (Dec 2025)

Genomic imprinting is the parent-of-origin specific monoallelic expression of genes that result from complex epigenetic interactions. It is often achieved by monoallelic 5-methylcytosine, resulting in the formation of differentially methylated regions (DMRs). These show a bias towards oocyte-derived methylation and survive reprogramming in the pre-implantation embryo. Imprinting is widespread in the human placenta. We have recently performed whole-genome screens for novel imprinted placenta-specific germline DMRs (gDMRs) by comparing methylomes of gametes, blastocysts and various somatic tissues, including placenta. We observe that, unlike conventional imprinting, for which methylation at gDMRs is observed in all tissues, placenta-specific imprinting is associated with transient gDMRs, present only in the pre-implantation embryo and extra-embryonic lineages. To expand the list of imprinted genes subject to placenta-specific imprinting, we reinvestigated our list of candidate loci and characterized two novel imprinted genes, and , both of which display polymorphic imprinting. Interrogation of placenta single-cell RNA-seq datasets, as well as cell-type methylation profiles, revealed complex cell-type specificity. We further interrogated their methylation and expression in placental samples from complicated pregnancies, but failed to identify differences between intrauterine growth restricted or pre-eclamptic samples and controls, suggesting they are not involved in these conditions.]]> Wed, 31 Dec 1969 19:00:00 EST Dysregulation of lncRNAs in NK cells from breast cancer patients: implications for NK cell functions. Rady M, Mohamed E, Khorshid O, Abou-Aisha K
Immunogenetics (Aug 2025)

Natural killer (NK) cells, a key component of the innate immune system, play a crucial role in detecting and eliminating cancer cells, contributing to cancer immune surveillance. Increasing evidence suggests that NK cell functions are regulated by epigenetic mechanisms, including the influence of long non-coding RNAs (lncRNAs). These lncRNAs, transcripts longer than 200 nucleotides, are emerging as important regulators of gene expression. In this study, we investigated the expression of 84 lncRNAs in NK cells isolated from the peripheral blood of patients with invasive breast cancer. Using lncRNA PCR array profiling, we identified 26 differentially expressed lncRNAs in circulating NK cells isolated from peripheral blood of breast cancer patients, with 10 genes showing significant downregulation and 16 genes showing significant upregulation. Gene ontology (GO) and functional enrichment analysis revealed that among the ten downregulated lncRNAs, four lncRNAs have deposited gene ontology terms and known biological functions. These lncRNAs are PTENP1-AS (fold change 0.27, P = 0.0206), TSIX (fold change 0.05, P = 0.0037), XIST (fold change 0.42, P = 0.007), and CCAT1 (fold change 0.09, P = 0.0191). On the other hand, among the 16 upregulated lncRNAs, five lncRNAs have deposited gene ontology terms and known biological functions. These lncRNAs are GNAS-AS1 (fold change 5.10, P = 0.0104), MEG3 (fold change 46.85, P = 0.0138), CDKN2B-AS1 (fold change 81.80, P = 0.0087), HOTAIR (fold change 6.86, P = 0.0042), and AIRN (fold change 7.97, P = 0.0379). Functional enrichment analysis indicated that the downregulated lncRNAs were mainly involved in biological processes such as chromatin organization, epigenetic regulation of gene expression, and dosage compensation via X chromosome inactivation, while the upregulated lncRNAs were linked to epigenetic regulation, genomic imprinting, and chromatin remodeling. These enrichments were identified using Bonferroni correction with an adjusted P-value < 0.05. Given the biological functions of the dysregulated lncRNAs in NK cells from breast cancer patients, this has the potential to significantly impact the antitumor functionality of NK cells, possibly contributing to the impaired immune surveillance and tumor control commonly observed in breast cancer patients. Understanding the dysregulation of lncRNAs in NK cells may provide critical insights into the mechanisms underlying impaired NK cell function in breast cancer, offering promising approaches for developing immunotherapies aiming at restoring NK cell activity in cancer patients.]]> Wed, 31 Dec 1969 19:00:00 EST The myoblast methylome: multiple types of associations with chromatin and transcription. Sen S, Lacey M, Baribault C, Ponnaluri VKC, Esteve PO, Ehrlich KC, Meletta M, Pradhan S, Ehrlich M
Epigenetics (Dec 2025)

Epigenetic changes are implicated in development, repair, and physiology of postnatal skeletal muscle (SkM). We generated methylomes for human myoblasts (SkM progenitor cells) and determined myoblast differentially methylated regions (DMRs) for comparison to the epigenomics and transcriptomics of diverse cell types. Analyses were from global genomic and single-gene perspectives and included reporter gene assays. One atypical finding was the association of promoter-adjacent hypermethylation in myoblasts with transcription turn-on, but at downmodulated levels, for certain genes (., and ). In contrast, brain-specific was in repressed chromatin and silent in most cell types but linked to hypermethylated DMRs specifically in myoblasts. The -linked DMRs might be needed because of the overlapping or nearby binding of myogenic differentiation protein 1 (MYOD). We found genome-wide overlap of DMRs with MYOD or CCCTC-binding factor (CTCF) binding sites in myoblasts that is consistent with the importance of MYOD, as well as CTCF, in organizing myoblast transcription-enhancing chromatin interactions. We also observed some gene upregulation correlated with a special association of regional DNA hypomethylation with H3K36me3, H3K27ac, and H3K4me1 enrichment. Our study highlights unusual relationships between epigenetics and gene expression that illustrate the interplay between DNA methylation and chromatin epigenetics in the regulation of transcription.]]> Wed, 31 Dec 1969 19:00:00 EST Ischemia/Reperfusion Injury and Outcomes in Liver Transplantation Assessed by Omics Technologies: Where Do We Stand? Giraudi PJ, Codotto G, Baccarani U, Baralle F, Gondolesi G, Licastro D, Tiribelli C
Transplantation (Aug 2025)

Liver transplantation faces several biological challenges, including those related to ischemia/reperfusion injury, graft rejection or tolerance, and disease recurrence. These processes significantly impact posttransplant outcomes and highlight the need for a deeper understanding to improve patient care. The progress of omics sciences has been remarkable over the past decades, and omics techniques are widely used in clinical investigations. In this review, we have explored and briefly described investigations using omics technologies (epigenomics, transcriptomics, and proteomics) to better understand the processes affecting liver transplantation. Additionally, we have highlighted recent studies that use cutting-edge omics technologies, including single-cell RNA sequencing, spatial transcriptomics, and multiplex proteomics, often integrated into multiomics approaches, which enable a more detailed and holistic analysis of the produced data, paving the way for the discovery of precise biomarkers for liver transplant monitoring and the development of novel therapies to prevent allograft rejection.]]> Wed, 31 Dec 1969 19:00:00 EST Differential methylation patterns in cord blood associated with prenatal exposure to neighborhood crime: an epigenome-wide association study and regional analysis. Martin CL, Chen J, D'Alessio AS, Ward-Caviness CK, Ye A, Lodge EK, Ghastine L, Dhingra R, Jima DD, Murphy SK, Hoyo C
Epigenetics (Dec 2025)

Exposure to prenatal social stressors during pregnancy is associated with adverse birth outcomes and has been linked to epigenetic changes in DNA methylation (DNAm); however, less understood is the effect of neighborhood-level stressors like crime during pregnancy on offspring DNAm. Using data from the Newborn Epigenetic Study, we conducted epigenome-wide and regional analyses of the association between exposure to neighborhood crime and DNAm in offspring cord blood using Illumina's HumanMethylation450k BeadChip among 185 mother-offspring pairs. Prenatal exposure to neighborhood crime at the census block group level was mapped to participants' residential addresses during the gestational window from the date of last menstrual period to delivery. Models for the epigenome-wide and regional analyses were adjusted for maternal age, race/ethnicity, education, smoking, cell-type composition, and offspring sex. Genetic influence and gene expression enrichment were assessed using methylation quantitative trait loci (mQTLs) and expression quantitative trait methylation (eQTMs) analyses. Functional enrichment was determined using Gene Ontology and KEGG databases. We did not find evidence of epigenome-wide associations between prenatal neighborhood crime exposure and DNAm; however, we identified nine differentially methylated regions (DMRs) comprising 51 CpG sites associated with neighborhood crime. CpG sites within significant differentially methylated regions were associated with mQTLs at birth and eQTMs upon further examination. KEGG analysis identified a significant Th1 and Th2 cell differentiation pathway. Our results suggest potential links between prenatal neighborhood crime exposure and offspring DNAm; however, additional research is needed in larger cohorts across wider geographic areas to confirm our results.]]> Wed, 31 Dec 1969 19:00:00 EST Integrating tRNA gene epigenomics and expression with codon usage unravels an intricate connection with translatome dynamics in . Silva HGS, Kimura S, Lima PLC, Pires DS, Waldor MK, da Cunha JPC
mBio (Aug 2025)

Codon usage bias impacts protein expression across all kingdoms of life, including trypanosomatids. These protozoa, such as the , primarily regulate their protein-coding genes through posttranscriptional mechanisms. Here, we integrated codon usage analyses with translatome data to investigate whether codon bias affects translated transcript expression levels in life forms. For the first time in trypanosomatids, tRNA sequencing was employed to reveal coadaptation between codon usage and anticodon availability. Despite notable differences in the proteomes of infective and noninfective forms, they exhibited similar pools of tRNAs and similar codon usage preferences, with notable differences in A-site ribosome occupancies. We developed pipelines to measure the adaptation of codons to their corresponding tRNA abundance pool (GM-tECA-Geometric Mean of tRNA Expression-Codon Adaptation) and to calculate the percentage of anticodon:codon base pairing modes in the genome. Our pipelines revealed an association between tRNA abundance, anticodon:codon pairing modes, and translated transcript levels. Highly expressed mRNAs are more adapted to tRNA abundance and favor either Watson-Crick or inosine pairing, whereas less expressed mRNAs exhibit lower adaptation to tRNA abundance and enrichment of codon with Wobble (G:U) pairing. Additionally, we observed that open chromatin levels of tRNA genes correlate with tRNA expression in noninfective forms, but not in infective forms, suggesting chromatin states do not control the tRNA pool in the latter. Overall, our findings suggest that protein expression in life forms is influenced by a combination of codon usage bias, tRNA abundance, and anticodon:codon pairing modes, but differences in ribosome A-site occupancies between life forms likely reflect additional layers of translation regulation.]]> Wed, 31 Dec 1969 19:00:00 EST use capsules, transporters, mobile genetic elements, and other evolutionary adaptations to survive antibiotics exposure in the absence of resistance genes. Mmatli M, Mbelle NM, Fourie B, Osei Sekyere J
Virulence (Dec 2025)

Whole-genome sequencing, transcriptomic profiling, and epigenomic analyses were performed. Phenotypic assays were used to evaluate the effects of various inhibitors on antibiotic susceptibility, while bioinformatic pipelines were used to characterize resistance determinants, virulence factors, and mobile genetic elements (MGEs).]]> Wed, 31 Dec 1969 19:00:00 EST Sex-stratified piRNA expression analysis reveals shared functional impacts of perinatal lead (Pb) exposure in murine hearts. Sala-Hamrick KE, Wang K, Perera BPU, Sartor MA, Svoboda LK, Dolinoy DC
Epigenetics (Dec 2025)

The landscape of PIWI-interacting RNA (piRNA) expression in the heart is poorly understood, particularly regarding sex differences. Altered piRNA expression has been reported in cardiovascular disease (CVD), and although exposure to the metal lead (Pb) is strongly associated with CVD risk, no studies have investigated Pb's effects on cardiac piRNAs. This study aimed to characterize piRNA expression in the murine heart and assess sex-specific effects of human-relevant maternal Pb exposure on adult offspring cardiac piRNA expression. piRNAs were identified from whole mouse hearts using sodium periodate exclusion of small RNA and subsequent sequencing. Control mice expressed 18,956 piRNAs in combined-sex analysis; sex-specific analyses revealed 9,231 piRNAs in female hearts and 5,972 piRNAs in male hearts. Genomic mapping showed 28-41% aligned to introns, while 12-28% mapped to exons. Comparing control and Pb-exposed hearts, we found more potential Pb-induced expression changes in females (847) compared to males (187) (p-value < 0.05 and |logFC| > 1). These piRNAs were significantly enriched near genes involved in biological processes related to heart function and CVD development, including mitochondrial function, energy metabolism, and cardiac muscle structure (FDR < 0.05). Overall, we characterized combined and sex-stratified piRNA expression in both control and Pb-exposed murine hearts. In addition to providing a foundation for sex-specific piRNA expression in the heart, these findings suggest a novel epigenetic mechanism by which developmental Pb exposure may impact CVD risk later in life. Future studies will link these sex-specific molecular changes to Pb-induced alterations in cardiac function.]]> Wed, 31 Dec 1969 19:00:00 EST Host-microbe multi-omics and succinotype profiling have prognostic value for future relapse in patients with inflammatory bowel disease. O'Sullivan J, Patel S, Leventhal GE, Fitzgerald RS, Laserna-Mendieta EJ, Huseyin CE, Konstantinidou N, Rutherford E, Lavelle A, Dabbagh K, DeSantis TZ, Shanahan F, Temko A, Iwai S, Claesson MJ
Gut Microbes (Dec 2025)

Crohn's disease (CD) and ulcerative colitis (UC) are chronic relapsing inflammatory bowel disorders (IBD), the pathogenesis of which is uncertain but includes genetic susceptibility factors, immune-mediated tissue injury and environmental influences, most of which appear to act via the gut microbiome. We hypothesized that host-microbe alterations could be used to prognostically stratify patients experiencing relapses up to four years after endoscopy. We therefore examined multiple omics data, including published and new datasets, generated from paired inflamed and non-inflamed mucosal biopsies from 142 patients with IBD (54 CD; 88 UC) and from 34 control (non-diseased) biopsies. The relapse-predictive potential of 16S rRNA gene and transcript amplicons (standing and active microbiota) were investigated along with host transcriptomics, epigenomics and genetics. While standard single-omics analysis could not distinguish between patients who relapsed and those that remained in remission within four years of colonoscopy, we did find an association between the number of flares and a patient's succinotype. Our multi-omics machine learning approach was also able to predict relapse when combining features from the microbiome and human host. Therefore multi-omics, rather than single omics, better predicts relapse within 4 years of colonoscopy, while a patient's succinotype is associated with a higher frequency of relapses.]]> Wed, 31 Dec 1969 19:00:00 EST AKR1B10 as a novel prognostic biomarker linking methylation and immune escape in hepatocellular carcinoma. Khan MN, Binli M, Juan H, Mengjia S, Shunyao W, Li X
Discov Oncol (Aug 2025)

]]> Wed, 31 Dec 1969 19:00:00 EST Perfluoroalkyl substance pollutants disrupt microglia function and trigger transcriptional and epigenomic changes. Cheng Y, Li JR, Yu H, Li S, Tychhon B, Cheng C, Weng YL
Toxicology (Nov 2025)

Per- and polyfluoroalkyl substances (PFAS), commonly referred to as "forever chemicals", are widely utilized in various industries and consumer products worldwide. Their exposure has been associated with numerous diseases and malignancies, including neurodevelopmental and neurodegenerative disorders. However, the molecular mechanisms underlying PFAS-induced adverse effects on the central nervous system (CNS) remain poorly understood. In this study, we investigated the transcriptomic and epigenetic changes in microglia exposed to perfluorooctane sulfonate (PFOS), a prevalent PFAS compound. Our findings demonstrate that 24-hour PFOS exposure (25 and 50 µM) disrupts the microglial transcriptome and compromises their homeostatic state, marked by increased inflammation and impaired actin cytoskeleton remodeling. Comparative analysis with in vivo transcriptional states revealed that PFOS-exposed microglia exhibit gene expression profiles resembling those of aged microglia. Additionally, profiling of active chromatin regions uncovered significant alterations in the H3K27ac landscape in PFOS-exposed microglia. Notably, these epigenetic disruptions persisted even after PFOS withdrawal, with a subset of H3K27ac-enriched regions remaining altered, suggesting the presence of lasting epigenetic scars. Furthermore, transcription factor analysis implicated the AP-1 and TEAD families as potential upstream regulators connecting the altered chromatin landscape to transcriptomic changes. Collectively, these findings provide mechanistic insights into how PFOS exposure disrupts microglial function and highlight its potential role in exacerbating neurodegenerative processes.]]> Wed, 31 Dec 1969 19:00:00 EST Chromatin remodeling in plants: Complex composition, mechanistic diversity and biological functions. Huang Y, Guo J, He XJ, Li C
Mol Plant (Aug 2025)

Chromatin remodeling complexes serve as crucial regulators of chromatin structure in eukaryotes, thereby governing transcription, DNA repair, and genome stability. Compared to chromatin remodelers in yeast and animals, plant chromatin remodelers exhibit both conserved and lineage-specific features, which facilitate unique adaptive responses. Cutting-edge approaches in biochemistry, epigenomics, and proteomics are revealing unprecedented insights into plant chromatin remodeling mechanisms, whereas genetic studies continue to demonstrate their essential roles in maintaining chromatin state homeostasis during plant growth and stress adaptation. This review synthesizes the current understanding of plant chromatin remodeling complexes, with particular emphasis on their specialized subunit compositions, mechanistic diversity, and integrative roles in epigenetic regulation. Furthermore, it highlights how these complexes interact with histone modifications, DNA methylation pathways, and transcription factor networks to orchestrate plant development and stress responses.]]> Wed, 31 Dec 1969 19:00:00 EST Deciphering sarcoidosis immunopathogenesis through systems biology. Jbeli AH, Crouser ED, Bhargava M
Curr Opin Pulm Med (Sep 2025)

Sarcoidosis is a complex, multisystem disease characterized by granulomatous inflammation and variable clinical outcomes. Its pathogenesis and progression are driven by intricate biological interactions, involving a complex interplay between patient-specific factors such as genetic background, sex, and environmental exposures, as well as epigenetic modifications that regulate gene expression and protein levels. These interconnected layers ultimately drive immune response to yet unidentified trigger(s), culminating in granuloma formation and, in some cases, with an aberrant repair response leading to irreversible organ dysfunction in some cases. In this review, we aim to synthesize recent multiomics research that unravels the underlying biological networks, offering a systems-level understanding of sarcoidosis.]]> Wed, 31 Dec 1969 19:00:00 EST Ageing versus developmental silencing: Answers from the epigenome. Sadler KC, Storer MA, Bayin NS
FEBS J (Aug 2025)

A strong regenerative capacity is a hallmark of youth. From the tadpole's tail to the mammalian brain, young animals of many species can repair or regrow damaged tissues more effectively than older animals. Here, we take a broad perspective on ageing, inclusive of the transition from the developmental processes of embryogenesis through maturation to adulthood, as well as the processes that occur as an animal reaches the end of its lifespan. In some cases, the loss of regenerative capacity occurs once development is complete, and in others it occurs in the latter part of the animal's life. Regardless, the loss of regenerative capacity is caused by a failure to activate genes required for successful regeneration. This, in part, can be attributed to restructuring of the epigenome.]]> Wed, 31 Dec 1969 19:00:00 EST Accounting for differences between Infinium MethylationEPIC v2 and v1 in DNA methylation-based tools. Zhuang BC, Jude MS, Konwar C, Yusupov N, Ryan CP, Engelbrecht HR, Whitehead J, Halberstam AA, MacIsaac JL, Dever K, Tran TK, Korinek K, Zimmer Z, Lee NR, McDade TW, Kuzawa CW, Huffman KM, Belsky DW, Binder EB, Czamara D, Korthauer K, Kobor MS
Life Sci Alliance (Sep 2025)

The recently launched Illumina Infinium MethylationEPIC v2.0 (EPICv2), successor of MethylationEPIC v1.0 (EPICv1), retains most of the probes in EPICv1, while expanding coverage of regulatory elements. The concordance between the two EPIC versions in DNA methylation-based tools has not yet been investigated. To address this, DNA methylation was profiled on both versions using matched blood samples across four cohorts spanning early to late adulthood. High concordance between versions at the array level but variable agreement at the individual probe level was noted. A significant contribution of the EPIC version to DNA methylation variation was observed, though it was to a smaller extent compared with sample relatedness and cell-type composition. Modest but significant differences in DNA methylation-based estimates between versions were observed, irrespective of the data preprocessing method used. Adjustments for EPIC version or calculation of estimates separately for each version largely mitigated these version-specific discordances. This work emphasizes the importance of accounting for EPIC version differences in research scenarios, especially in meta-analyses and longitudinal studies that require data harmonization across versions.]]> Wed, 31 Dec 1969 19:00:00 EST Beyond Genes: Mechanistic and Epidemiological Insights into Paternal Environmental Influence on Offspring Health. Rotem RS, Hernández-Díaz S, Hauser R, Weisskopf MG
Curr Environ Health Rep (Aug 2025)

PURPOSE OF REVIEW: It is widely accepted that maternal genes and the in-utero environment can impact offspring's health. While fathers have long been considered mere conduits of genetic information, emerging evidence suggests that the paternal preconception environment can also affect offspring's health. This review delves into the biological mechanisms, beyond DNA inheritance, by which paternal preconception exogenous exposures can shape offspring outcomes, and factors that influence these mechanisms. We also discuss practical and methodological hurdles in epidemiological studies of male lineage inheritance.]]> Wed, 31 Dec 1969 19:00:00 EST Mosaicism for Genome Wide Homozygosity Identified as an Incidental Finding in Two Apparently Healthy Pregnant Women. Haskell GT, Askree SH, Kline L, Hasadsri L, Cabral H, Gadi I, Schwartz S
Am J Med Genet A (Sep 2025)

Uniparental Disomy (UPD) occurs when both copies of a chromosome or chromosomal segment originate from only one parent. Mosaic genome-wide UPD (mos gwUPD) is typically identified in cases of fetal demise and placental dysplasia or in prenatal cases, where imprinting effects are associated with abnormal ultrasound findings. Children with mos gwUPD and clinical features due to UPD-associated imprinting effects (especially Beckwith-Wiedemann syndrome) have been reported; however, reports of adults with mos gwUPD are rare. Here we describe mos gwUPD in two apparently healthy pregnant adult women. Carrier testing noted variants with skewed allelic ratios outside of the normal heterozygous range, prompting further testing. Single nucleotide polymorphism (SNP) microarray identified mosaicism for gwUPD in both individuals, present at 85% and 90%, respectively, in blood, with varying percentages in other tissues. Neither woman displayed clinical features that would be expected with gwUPD at the time of testing, although retrospective careful personal history was consistent. Both women had uneventful pregnancies and delivered full-term healthy infants. These two cases demonstrate that mos gwUPD can be an incidental finding identified in apparently healthy adult women. Clinical follow-up is important for tumor monitoring, genetic counseling, and monitoring of future pregnancies due to mos gwUPD in the maternal endometrial tissue.]]> Wed, 31 Dec 1969 19:00:00 EST Urine cf-nucleosomes: A non-invasive window into human physiology and disease. Lotem M, Sharkia I, Azria B, Harpenas E, Ormianer M, Rosen H, Falick-Michaeli T, Friedman N
Cell Genom (Aug 2025)

Urine contains fragments of cell-free DNA (cfDNA) that offer molecular insights into processes within the urinary system and the body. It remains unclear whether these fragments exist as chromatin and retain chromatin modifications from their cells of origin. Here, we employ cell-free chromatin immunoprecipitation followed by sequencing (cfChIP-seq) on human urine to address this issue. We show that cf-nucleosomes can be captured from urine and preserve histone modifications associated with gene activation and repression. Analysis in healthy individuals reveals distinct tissue contributions to urine cf-nucleosomes, including a kidney-derived population not detected in matched exfoliated cells or plasma. This suggests that kidney filtration largely excludes plasma cf-nucleosomes. In patients with bladder cancer, urine cf-nucleosomes reflect tumor-associated transcriptional programs and immune responses. These findings highlight the utility of urine cf-nucleosomes as accessible, non-invasive biomarkers for studying renal physiology and monitoring urinary pathologies.]]> Wed, 31 Dec 1969 19:00:00 EST