Human molecular genetics最新文献

{"title":"Alternative polyadenylation shapes the molecular and clinical features of lung adenocarcinoma.","authors":"Yipeng Gao, Vikram R Shaw, Christopher I Amos","doi":"10.1093/hmg/ddae150","DOIUrl":"10.1093/hmg/ddae150","url":null,"abstract":"<p><p>Alternative polyadenylation (APA) is a major mechanism of post-transcriptional regulation that affects mRNA stability, localization and translation efficiency. Previous pan-cancer studies have revealed that APA is frequently disrupted in cancer and is associated with patient outcomes. Yet, little is known about cancer type-specific APA alterations. Here, we integrated RNA-sequencing data from a Korean cohort (GEO: GSE40419) and The Cancer Genome Atlas (TCGA) to comprehensively analyze APA alterations in lung adenocarcinomas (LUADs). Comparing expression levels of core genes involved in polyadenylation, we find that overall, the set of 28 of 31 genes are upregulated, with CSTF2 particularly upregulated. We observed broad and recurrent APA changes in LUAD growth-promoting genes. In addition, we find enrichment of APA events in genes associated with known LUAD pathways and an increased heterogeneity in polyadenylation (polyA) site usage of proliferation-associated genes. Upon further investigation, we report smoking-specific APA changes are also highly relevant to LUAD development. Overall, our in-depth analysis reveals APA as an important driver for the molecular and clinical features of lung adenocarcinoma.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"1-10"},"PeriodicalIF":3.1,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterisation of LGP2 complex multitranscript system in humans: role in the innate immune response and evolution from non-human primates.","authors":"Jorge Martinez-Laso, Isabel Cervera, Marina S Martinez-Carrasco, Veronica Briz, Celia Crespo-Bermejo, Clara Sánchez-Menéndez, Guiomar Casado-Fernández, Montserrat Torres, Mayte Coiras","doi":"10.1093/hmg/ddae155","DOIUrl":"10.1093/hmg/ddae155","url":null,"abstract":"<p><p>Retinoic acid inducible gene I (RIG-I)-like receptors (RLRs), including RIG-I, MDA5 and LGP2, recognize viral RNA to mount an antiviral interferon (IFN) response RLRs share three different protein domains: C-terminal domain, DExD/H box RNA helicase domain, and an N-terminal domain with two tandem repeats (CARDs). LGP2 lacks tandem CARD and is not able to induce an IFN response. However, LGP2 positively enhances MDA5 and negatively regulates RIG-I signaling. In this study, we determined the LGP2 alternative transcripts in humans to further comprehend the mechanism of its regulation, their evolutionary origin, and the isoforms functionallity. The results showed new eight alternative transcripts in the samples tested. The presence of these transcripts demonstrated that the main mechanisms for the regulation of LGP2 expression are both by insertion of introns and by the loss of exons. The phylogenetic analysis of the comparison between sequences from exon 1 to exon 3 of humans and those previously described in non-human primates showed three well-differentiated groups (lineages) originating from gorillas, suggesting that the transspecies evolution has been maintained for 10 million years. The corresponding protein models (isoforms) were also established, obtaining four isoforms: one complete and three others lacking the C-terminal domain or this domain and the partial or total He2 Helicase domain, which would compromise the functionality of LGP2. In conclusion, this is the first study that elucidate the large genomic organization and complex transcriptional regulation of human LGP2, its pattern of sequence generation, and a mode of evolutionary inheritance across species.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"11-20"},"PeriodicalIF":3.1,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"4-Phenylbutyric acid mitigates ER stress-induced neurodegeneration in the spinal cords of a GM2 gangliosidosis mouse model.","authors":"Fiona E Weaver, Elizabeth White, Allyson M Peek, Colin A Nurse, Richard C Austin, Suleiman A Igdoura","doi":"10.1093/hmg/ddae153","DOIUrl":"10.1093/hmg/ddae153","url":null,"abstract":"<p><p>Sandhoff disease (SD), a fatal and rare lysosomal storage disorder (LSD), is caused by a deficiency of the enzyme β-hexosaminidase B and leads to severe accumulation of GM2 gangliosides in lysosomes, primarily within the central nervous system (CNS). This accumulation results in severe neurological impairment, lower motor neuron disease, and death. Currently, there are no effective therapies available for SD. Here, we explored the role of endoplasmic reticulum (ER) stress in the spinal cord during disease progression in an established mouse model of SD and revealed the beneficial outcome of off-label treatment with the FDA-approved drug, 4-phenylbutyric acid (4-PBA). We analyzed the expression and localization of ER stress and cellular apoptosis markers, which revealed significant upregulation of these factors within motor neurons. Additionally, we observed a > 50% reduction in neuronal numbers throughout all spinal cord regions. Our studies also tested the impact of the chemical chaperone 4-PBA on ER stress in mice, and following administration, we observed significant improvements in motor neuromuscular function and life span throughout disease progression. 4-PBA treatment significantly reduced apoptosis in spinal cord neurons and increased the number of choline acetyltransferase (ChAT)-positive neurons, with little effect on astrogliosis or sensory interneurons. Overall, this study provides strong evidence for the role of chronic ER stress in the pathophysiology of SD and highlights 4-PBA as a promising therapeutic treatment for SD and potentially other related LSDs.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"32-46"},"PeriodicalIF":3.1,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of paired immunoglobin-like type 2 receptor B gene associated with age-related macular degeneration impairs photoreceptor function in mouse retina.","authors":"Partha Narayan Dey, Nivedita Singh, Lina Zelinger, Zachary Batz, Jacob Nellissery, Noor D White Carreiro, Haohua Qian, Tiansen Li, Robert N Fariss, Lijin Dong, Anand Swaroop","doi":"10.1093/hmg/ddae161","DOIUrl":"10.1093/hmg/ddae161","url":null,"abstract":"<p><p>Genome-wide association studies have uncovered mostly non-coding variants at over 60 genetic loci linked to susceptibility for age-related macular degeneration (AMD). To ascertain the causal gene at the PILRB/PILRA locus, we used a CRISPR strategy to produce germline deletions in the mouse paired immunoglobin-like type 2 receptor (Pilr) genes that encode highly related activating (PILRB) and inhibitory (PILRA) receptors. We show that a combined loss of Pilrb1 and Pilrb2, but not Pilra, leads to an early but relatively stationary defect as the electroretinography (ERG) amplitudes of Pilrb1/2-/- mice exhibit a marked reduction as early as postnatal day 15 and do not show additional significant decrease at 3 and 12-months. No alterations are evident in Müller glia, microglia, bipolar, amacrine and horizontal cells based on immunohistochemistry using cell-type specific markers. PILRB immunostaining is specifically detected at the proximal part of photoreceptor outer segment. Reduced expression of select calcium-regulated phototransduction and synapse-associated proteins, including GCAP1 and 2, PDE6b, AIPL1, PSD95, and CTBP1 indicates dysregulation of calcium homeostasis as a possible mechanism of retinal phenotype in Pilrb1/2-/- mice. Our studies suggest a novel function of PILRB in retinal photoreceptors and an association of PILRB, but not PILRA, with AMD pathogenesis.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"64-76"},"PeriodicalIF":3.1,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stem cell models of TAFAZZIN deficiency reveal novel tissue-specific pathologies in Barth syndrome.","authors":"Olivia Sniezek Carney, Kodi W Harris, Yvonne Wohlfarter, Kyuna Lee, Grant Butschek, Arianna F Anzmann, Anne Hamacher-Brady, Markus A Keller, Hilary J Vernon","doi":"10.1093/hmg/ddae152","DOIUrl":"10.1093/hmg/ddae152","url":null,"abstract":"<p><p>Barth syndrome (BTHS) is a rare mitochondrial disease caused by pathogenic variants in the gene TAFAZZIN, which leads to abnormal cardiolipin (CL) metabolism on the inner mitochondrial membrane. Although TAFAZZIN is ubiquitously expressed, BTHS involves a complex combination of tissue specific phenotypes including cardiomyopathy, neutropenia, skeletal myopathy, and growth delays, with a relatively minimal neurological burden. To understand both the developmental and functional effects of TAZ-deficiency in different tissues, we generated isogenic TAZ knockout (TAZ-KO) and WT cardiomyocytes (CMs) and neural progenitor cells (NPCs) from CRISPR-edited induced pluripotent stem cells (iPSCs). In TAZ-KO CMs we discovered evidence of dysregulated mitophagy including dysmorphic mitochondria and mitochondrial cristae, differential expression of key autophagy-associated genes, and an inability of TAZ-deficient CMs to properly initiate stress-induced mitophagy. In TAZ-deficient NPCs we identified novel phenotypes including a reduction in CIV abundance and CIV activity in the CIII2&CIV2 intermediate complex. Interestingly, while CL acyl chain manipulation was unable to alter mitophagy defects in TAZ-KO CMs, we found that linoleic acid or oleic acid supplementation was able to partially restore CIV abundance in TAZ-deficient NPCs. Taken together, our results have implications for understanding the tissue-specific pathology of BTHS and potential for tissue-specific therapeutic targeting. Moreover, our results highlight an emerging role for mitophagy in the cardiac pathophysiology of BTHS and reveal a potential neuron-specific bioenergetic phenotype.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"101-115"},"PeriodicalIF":3.1,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 susceptibility and therapeutic targets for kidney stones through proteome-wide Mendelian randomization.","authors":"Qinhong Jiang, Xiaozhe Su, Wenbiao Liao, Ziqi He, Yunhan Wang, Rong Jiang, Caitao Dong, Sixing Yang","doi":"10.1093/hmg/ddae159","DOIUrl":"10.1093/hmg/ddae159","url":null,"abstract":"<p><p>Given the high recurrence rate of kidney stones, surgical lithotripsy and stone removal are not the ultimate treatments for kidney stones. There's an urgent need to explore the genetic mechanisms behind the susceptibility to kidney stones and to identify potential targets for prevention, to reduce the renal damage caused by recurrent stone formation. In this study, we screened 4548 circulating proteins using proteome-wide Mendelian Randomization (MR) to find proteins with a causal relationship to kidney stone risk. Additionally, proteome-wide association study (PWAS) and colocalization analysis were used to validate and prioritize candidate proteins. Moreover, downstream analyses including single-cell analysis, enrichment analysis, protein-protein interaction (PPI), and druggability analysis were conducted on the proteins causally related to kidney stones, to further explore the genetic mechanisms of susceptibility and the potential of proteins as drug targets. Ultimately, 22 target proteins associated with the risk of kidney stones were identified. Six plasma proteins (COLGALT1, CLMP, LECT1, ITIH1, CDHR3, CPLX2) were negatively correlated with kidney stone risk, while the genetic overexpression of 16 target proteins (GJA1, STOM, IRF9, F9, TMPRSS11D, ADH1B, SPINK13, CRYBB2, TNS2, DOCK9, OXSM, MST1, IL2, LMAN2, ITIH3, KLRF1) increased the risk of kidney stones. Based on the PWAS and colocalization analysis results, the 22 target proteins were classified into 3 tiers: IL2, CPLX2, and LMAN2 as tier 1 proteins with the most compelling evidence, MST1, ITIH1, and ITIH3 as tier 2 proteins, and the rest as tier 3 proteins. Enrichment analysis and PPI showed that target proteins mainly affect the occurrence of kidney stones through leukocyte activation and cell junction assembly. Druggability analysis suggested that IL2, MST1, and ITIH1 have potential as drug targets, and potential drugs were evaluated through molecular docking. In summary, this study employed multiple analytical methods to screen plasma proteins related to susceptibility to kidney stones, providing new insights into the genetic mechanisms of kidney stones and potential targets for treatment and prevention.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"47-63"},"PeriodicalIF":3.1,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SMN depletion impairs skeletal muscle formation and maturation in a mouse model of SMA.","authors":"Hong Liu, Lucia Chehade, Marc-Olivier Deguise, Yves De Repentigny, Rashmi Kothary","doi":"10.1093/hmg/ddae162","DOIUrl":"10.1093/hmg/ddae162","url":null,"abstract":"<p><p>Spinal muscular atrophy (SMA) is characterized by low levels of the ubiquitously expressed Survival Motor Neuron (SMN) protein, leading to progressive muscle weakness and atrophy. Skeletal muscle satellite cells play a crucial role in muscle fiber maintenance, repair, and remodelling. While the effects of SMN depletion in muscle are well documented, its precise role in satellite cell function remains largely unclear. Using the Smn2B/- mouse model, we investigated SMN-depleted satellite cell biology through single fiber culture studies. Myofibers from Smn2B/- mice were smaller in size, shorter in length, had reduced myonuclear domain size, and reduced sub-synaptic myonuclear clusters-all suggesting impaired muscle function and integrity. These changes were accompanied by a reduction in the number of myonuclei in myofibers from Smn2B/- mice across all disease stages examined. Although the number of satellite cells in myofibers was significantly reduced, those remaining retained their capacity for myogenic activation and proliferation. These findings support the idea that a dysregulated myogenic process could be occurring as early in muscle stem cells during muscle formation and maturation in SMA. Targeting those pathways could offer additional options for combinatorial therapies for SMA.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"21-31"},"PeriodicalIF":3.1,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide association study of urinary cadmium levels in current smokers from the multiethnic cohort study.","authors":"Shannon M Sullivan, Sharon E Murphy, Daniel O Stram, Lynne R Wilkens, Christopher A Haiman, Loïc Le Marchand, Irina Stepanov, S Lani Park","doi":"10.1093/hmg/ddae202","DOIUrl":"https://doi.org/10.1093/hmg/ddae202","url":null,"abstract":"<p><strong>Background: </strong>Cadmium (Cd), classified as an International Agency for Research on Cancer (IARC) Group 1 human carcinogen, is present in cigarette smoke. Recent studies have illustrated the potential role of genetics in influencing Cd biomarker levels.</p><p><strong>Methods: </strong>We conducted a genome-wide association study (GWAS) of urinary Cd levels in 1977 current smokers from the Multiethnic Cohort Study, comprising participants from five different racial and ethnic groups. Linear regression models were adjusted for age at urine collection, sex, self-reported race/ethnicity, and the top ten leading principal components.</p><p><strong>Results: </strong>Among the 11 710 497 single nucleotide polymorphisms (SNP) analyzed, no associations with urinary Cd reached genome-wide significance (P < 5.0 × 10-8). Notably, five variants demonstrated suggestive associations with urinary Cd levels (P < 1.0 × 10-6). Lead variants included: rs10097646 in the SCARA gene at 8q13.2 (P = 2.62 × 10-7); rs7444817 in the NIPBL gene at 5p13.2 (P = 3.10 × 10-7), rs830422 in the SPINK4 gene at 9q13.2 (P = 4.89 × 10-7); chrX:145489901 in the SLC9A7 gene at Xq121.1 (P = 5.38 × 10-7); and rs73074456 at 5p13.3 (P = 5.86 × 10-7).</p><p><strong>Conclusions: </strong>Our GWAS of urinary Cd levels in a diverse population of people who smoke, revealed suggestive associations with variants in SCARA5, NIPBL, SPINK4, SLC9A7, and 5p13.3. These findings underscore the potential role of genetic factors in understanding and mitigating the health risks associated with internal dose of carcinogens, particularly in the context of tobacco-related carcinogens.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression variation of long noncoding RNAs in dopaminergic cells-derived from stem cells and their MPP+ induced PD models.","authors":"Setareh Behrouzi Abady Pamsary, Fariba Esmaeili, Fariba Dehghanian, Mohammad Hadi Bahadori","doi":"10.1093/hmg/ddae192","DOIUrl":"https://doi.org/10.1093/hmg/ddae192","url":null,"abstract":"<p><p>Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder characterized by the progressive loss of nigrostriatal dopaminergic neurons (DA) which can be caused by environmental and genetic factors. lncRNAs have emerged as an important regulatory layer in neurodegenerative disorders, including PD. In this study, we investigated and validated lncRNAs that may serve as diagnostic or therapeutic targets for PD. Key genes associated with midbrain and DA cells were screened by differential gene expression analysis on GSE213100 dataset and candidate lncRNAs were selected for further examination. P19 cells were differentiated into DA cells and received treatment with MPP+ to induce PD-like cytotoxic events, which were confirmed by light microscopy, RT-qPCR, immunofluorescence and flow cytometry. Then, the cells were used to investigate the changes of lncRNAs Malat1, Norad, Snhg1 and Meg3. Here we found that the neuronal phenotype was mainly observed on the 12th day of differentiation and the number of DA markers significantly decreased in PD model cells compared with the control group. Moreover, the expression levels of Meg3, Norad, and Snhg1 were decreased by MPP+ whereas Malat1 level was noticeably higher in MPP+ cells compared to DA cells and the control group. In conclusion, the expression level of lncRNAs was able to show a significant difference between differentiated dopaminergic cells and their Parkinsonian model, thereby improving our understanding of the molecular pathogenesis of PD.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reciprocal and non-reciprocal effects of clinically relevant SETBP1 protein dosage changes.","authors":"Lilit Antonyan, Xin Zhang, Anjie Ni, Huashan Peng, Shaima Alsuwaidi, Peter Fleming, Ying Zhang, Amelia Semenak, Julia Macintosh, Hanrong Wu, Nuwan C Hettige, Malvin Jefri, Carl Ernst","doi":"10.1093/hmg/ddaf003","DOIUrl":"https://doi.org/10.1093/hmg/ddaf003","url":null,"abstract":"<p><p>Many genes in the human genome encode proteins that are dosage sensitive, meaning they require protein levels within a narrow range to properly execute function. To investigate if clinically relevant variation in protein levels impacts the same downstream pathways in human disease, we generated cell models of two SETBP1 syndromes: Schinzel-Giedion Syndrome (SGS) and SETBP1 haploinsufficiency disease (SHD), where SGS is caused by too much protein, and SHD is caused by not enough SETBP1. Using patient and sex-matched healthy first-degree relatives from both SGS and SHD SETBP1 cases, we assessed how SETBP1 protein dosage affects downstream pathways in human forebrain progenitor cells. We find that extremes of SETBP1 protein dose reciprocally influence important signalling molecules such as AKT, suggesting that the SETBP1 protein operates within a narrow dosage range and that extreme doses are detrimental. We identified SETBP1 nuclear bodies as interacting with the nuclear lamina and suggest that SETBP1 may organize higher order chromatin structure via links to the nuclear envelope. SETBP1 protein doses may exert significant influence on global gene expression patterns via these SETBP1 nuclear bodies. This work provides evidence for the importance of SETBP1 protein dose in human brain development, with implications for two neurodevelopmental disorders.</p>","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}