Pub Date : 2025-09-12DOI: 10.1016/j.humgen.2025.201481
Zahra Taherian-Esfahani, Hamideh Namazi
Beta thalassemia is a common autosomal recessive disorder. In this study, we report a rare beta globin gene variant, HBB: c.60C>T, identified in an Afghan Family.
Sequencing of a 30 year old pregnant woman and her children showed that this synonymous variant, when present alongside other pathogenic HBB mutations, does not affect beta globin production. In the proband, hematological findings were not consistent with a beta thalassemia minor phenotype. Although this variant has been reported in Clinvar as a variant of uncertain significance (VUS), our findings support its classification as likely benign.
{"title":"Identification of a rare synonymous beta globin variant, HBB: c.60C>T in an Afghan Family as a benign variant","authors":"Zahra Taherian-Esfahani, Hamideh Namazi","doi":"10.1016/j.humgen.2025.201481","DOIUrl":"10.1016/j.humgen.2025.201481","url":null,"abstract":"<div><div>Beta thalassemia is a common autosomal recessive disorder. In this study, we report a rare beta globin gene variant, <em>HBB</em>: c.60C>T, identified in an Afghan Family.</div><div>Sequencing of a 30 year old pregnant woman and her children showed that this synonymous variant, when present alongside other pathogenic HBB mutations, does not affect beta globin production. In the proband, hematological findings were not consistent with a beta thalassemia minor phenotype. Although this variant has been reported in Clinvar as a variant of uncertain significance (VUS), our findings support its classification as likely benign.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201481"},"PeriodicalIF":0.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-12DOI: 10.1016/j.humgen.2025.201478
Elnaz Akbari , Asal Asghari Sarfaraz , Mortaza Bonyadi , Mohammad Barzegar
TANGO2-related disorder exhibits significant genotypic and phenotypic heterogeneity, and the clinical significance of novel variants often requires confirmation through detailed case reporting. This case report describes a female child born to consanguineous parents with an unremarkable prenatal and perinatal history. Initial development was normal, but by the second year of life, she exhibited developmental regression, and seizures, which were controlled with levetiracetam. At age 5, she presented with acute encephalopathy, dark urine, rhabdomyolysis, hypoglycemia, and hyperammonemia following a febrile illness. Whole-exome sequencing (WES) identified a novel homozygous TANGO2 variant (c.263G > A, p.Arg88Gln), confirmed via Sanger sequencing, with both parents being heterozygous carriers. Bioinformatics analysis predicted pathogenic effects, including potential exon skipping and protein structural alterations. The variant was absent in 430 ethnically matched controls and major population databases (gnomAD, 1000 Genomes), supporting its pathogenicity. Despite management, the patient experienced recurrent metabolic crises and ultimately succumbed to severe rhabdomyolysis and renal failure at age 8. This case underscores the severe phenotypic consequences of biallelic TANGO2 mutations, including developmental delay, metabolic instability, and early mortality, while highlighting the importance of genetic diagnosis in unexplained pediatric encephalopathies.
tango - 2相关疾病表现出显著的基因型和表型异质性，新变异的临床意义往往需要通过详细的病例报告来证实。本病例报告描述了一个女婴出生的近亲父母与一个不起眼的产前和围产期历史。最初发育正常，但到了第二年，她表现出发育倒退和癫痫发作，用左乙拉西坦控制。5岁时，她表现为急性脑病、尿色深、横纹肌溶解、低血糖和发热性疾病后的高氨血症。全外显子组测序（WES）鉴定出一种新的纯合子TANGO2变异（c.263G > a, p.Arg88Gln），通过Sanger测序证实，父母双方都是杂合子携带者。生物信息学分析预测致病效应，包括潜在的外显子跳变和蛋白质结构改变。在430个种族匹配的对照和主要人群数据库（gnomAD， 1000个基因组）中未发现该变异，支持其致病性。尽管进行了治疗，患者还是经历了反复的代谢危机，最终在8岁时死于严重的横纹肌溶解和肾功能衰竭。该病例强调了双等位基因TANGO2突变的严重表型后果，包括发育迟缓、代谢不稳定和早期死亡，同时强调了基因诊断在不明原因的儿科脑病中的重要性。
{"title":"Clinical, genetic, and bioinformatics analysis of a novel TANGO2 mutation (c.263G > A) in an Iranian Azeri Turkish child with lethal metabolic encephalopathy","authors":"Elnaz Akbari , Asal Asghari Sarfaraz , Mortaza Bonyadi , Mohammad Barzegar","doi":"10.1016/j.humgen.2025.201478","DOIUrl":"10.1016/j.humgen.2025.201478","url":null,"abstract":"<div><div>TANGO2-related disorder exhibits significant genotypic and phenotypic heterogeneity, and the clinical significance of novel variants often requires confirmation through detailed case reporting. This case report describes a female child born to consanguineous parents with an unremarkable prenatal and perinatal history. Initial development was normal, but by the second year of life, she exhibited developmental regression, and seizures, which were controlled with levetiracetam. At age 5, she presented with acute encephalopathy, dark urine, rhabdomyolysis, hypoglycemia, and hyperammonemia following a febrile illness. Whole-exome sequencing (WES) identified a novel homozygous <em>TANGO2</em> variant (c.263G > A, p.Arg88Gln), confirmed via Sanger sequencing, with both parents being heterozygous carriers. Bioinformatics analysis predicted pathogenic effects, including potential exon skipping and protein structural alterations. The variant was absent in 430 ethnically matched controls and major population databases (gnomAD, 1000 Genomes), supporting its pathogenicity. Despite management, the patient experienced recurrent metabolic crises and ultimately succumbed to severe rhabdomyolysis and renal failure at age 8. This case underscores the severe phenotypic consequences of biallelic <em>TANGO2</em> mutations, including developmental delay, metabolic instability, and early mortality, while highlighting the importance of genetic diagnosis in unexplained pediatric encephalopathies.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201478"},"PeriodicalIF":0.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gliomas are one of the most common primary brain tumors and their prognosis is highly dependent on patient-specific factors. The objective of our review is to detail how age influences the epidemiology, molecular pathogenesis, prognosis, and treatment of gliomas. A literature search was conducted for adult and pediatric gliomas (PG) at Google Scholar and PubMed, with relevant keywords like gliomas, World Health Organization (WHO) classification, histology, and treatment, etc., and papers published until 2023 were reviewed. It was found that males and non-Hispanic white people are particularly at risk in both age categories. People with poor socioeconomic status are more likely to have PG. While the overall incidence of adult gliomas has been declining, glioblastoma (GBM) occurrence has been rising. The latest WHO classification of central nervous system (CNS) tumors has highlighted the molecular aberrations to further stratify adult and PG, and literature review revealed how each type has unique histological features. The first line treatment for both groups is surgery followed by adjuvant radio- and chemotherapy, although radiotherapy use for children remains controversial. PGs can also be treated with targeted therapy of the Mitogen-activated protein kinase (MAPK) pathway and currently, anti-cancer drugs are being investigated. By juxtaposing pediatric and adult gliomas, several theories can be proposed about how certain gliomas develop at specific ages, how they vary in their presentations and management, and what can be further explored to improve patient outcomes. This information is pivotal for understanding not only how age influences the development of certain mutations but also how treatment varies according to a patient's age.
{"title":"Glioma in different life stages: A comparative analysis of adult and pediatric tumors","authors":"Ajia Ashraf , Armeen Ashraf , Lubna Khan , Shahrukh Shaikh , Farina Hanif","doi":"10.1016/j.humgen.2025.201476","DOIUrl":"10.1016/j.humgen.2025.201476","url":null,"abstract":"<div><div>Gliomas are one of the most common primary brain tumors and their prognosis is highly dependent on patient-specific factors. The objective of our review is to detail how age influences the epidemiology, molecular pathogenesis, prognosis, and treatment of gliomas. A literature search was conducted for adult and pediatric gliomas (PG) at Google Scholar and PubMed, with relevant keywords like gliomas, World Health Organization (WHO) classification, histology, and treatment, etc., and papers published until 2023 were reviewed. It was found that males and non-Hispanic white people are particularly at risk in both age categories. People with poor socioeconomic status are more likely to have PG. While the overall incidence of adult gliomas has been declining, glioblastoma (GBM) occurrence has been rising. The latest WHO classification of central nervous system (CNS) tumors has highlighted the molecular aberrations to further stratify adult and PG, and literature review revealed how each type has unique histological features. The first line treatment for both groups is surgery followed by adjuvant radio- and chemotherapy, although radiotherapy use for children remains controversial. PGs can also be treated with targeted therapy of the Mitogen-activated protein kinase (MAPK) pathway and currently, anti-cancer drugs are being investigated. By juxtaposing pediatric and adult gliomas, several theories can be proposed about how certain gliomas develop at specific ages, how they vary in their presentations and management, and what can be further explored to improve patient outcomes. This information is pivotal for understanding not only how age influences the development of certain mutations but also how treatment varies according to a patient's age.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201476"},"PeriodicalIF":0.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A chronic progressive neurodegenerative disorder, Parkinson's disease (PD) is associated with motor impairment with elderly people. The cytokines and chemokines network are very complex and participate to balance the proinflammatory processes, apoptosis and cell existence. So, it is necessary to unravel the inflammatory process in PD. Increased nuclear factor kappa B, expression of cytokines, increased activation of microglia participate in the inflammatory process of PD. The activation of glial fibrillary acidic protein (GFAP) gene and protein results in the activation of astroglial cells which ends up with neurodegeneration and central nervous damage. Natural compounds carry a huge amount of antioxidant properties with health benefits and phenolic compounds is a natural dietary source.
Methods
Quantitative determination of serum CRP, immunohistochemical study was carried out along with the molecular studies such as (RT-PCR) and western blotting.
Results
Sesamol treatment decreased the C- Reactive protein level in serum of experimental animals. Sesamol also increased the tyrosine hydroxylase cells in rotenone-induced animals. The gene and protein expressions of NF-κB (p65), Tumor necrosis factor-α, cyclo oxygeanse-2, inducible nitric oxide synthase, interleukin-1β and GFAP were also reduced in SES treated animals.
Conclusion
Sesamol served as an anti-inflammatory compound in ROT-induced animal model of PD. This work mainly concentrates on the molecular mechanism of phenolic compound sesamol on rotenone induced PD.
{"title":"Effectiveness of sesamol in alleviating neuroinflammation associated with Parkinson's disease","authors":"Rohini Durairaj , Manjunathan Jagadeesan , S. Shireen Farhana , Shobana Chandrasekar , Usharani Boopathy , Parthiban Brindha Devi , Pasiyappazham Ramasamy","doi":"10.1016/j.humgen.2025.201474","DOIUrl":"10.1016/j.humgen.2025.201474","url":null,"abstract":"<div><h3>Objectives</h3><div>A chronic progressive neurodegenerative disorder, Parkinson's disease (PD) is associated with motor impairment with elderly people. The cytokines and chemokines network are very complex and participate to balance the proinflammatory processes, apoptosis and cell existence. So, it is necessary to unravel the inflammatory process in PD. Increased nuclear factor kappa B, expression of cytokines, increased activation of microglia participate in the inflammatory process of PD. The activation of glial fibrillary acidic protein (GFAP) gene and protein results in the activation of astroglial cells which ends up with neurodegeneration and central nervous damage. Natural compounds carry a huge amount of antioxidant properties with health benefits and phenolic compounds is a natural dietary source.</div></div><div><h3>Methods</h3><div>Quantitative determination of serum CRP, immunohistochemical study was carried out along with the molecular studies such as (RT-PCR) and western blotting.</div></div><div><h3>Results</h3><div>Sesamol treatment decreased the C- Reactive protein level in serum of experimental animals. Sesamol also increased the tyrosine hydroxylase cells in rotenone-induced animals. The gene and protein expressions of NF-κB (p65), Tumor necrosis factor-α, cyclo oxygeanse-2, inducible nitric oxide synthase, interleukin-1β and GFAP were also reduced in SES treated animals.</div></div><div><h3>Conclusion</h3><div>Sesamol served as an anti-inflammatory compound in ROT-induced animal model of PD. This work mainly concentrates on the molecular mechanism of phenolic compound sesamol on rotenone induced PD.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201474"},"PeriodicalIF":0.7,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-08DOI: 10.1016/j.humgen.2025.201473
Paramasivam Arumugam , Chandra Pandi , Vijayashree Priyadharsini Jayaseelan
Objective
This study examines the oncogenic role of cleavage stimulation factor subunit 2 (CSTF2), a newly identified N6-methyladenosine (m6A)-binding protein in the pathogenesis of head and neck squamous cell carcinoma (HNSCC). We also explored its amplification-driven overexpression, its prognostic significance, and its mechanistic contributions to tumor aggressiveness.
Method
A dataset of patients with HNSCC was used from the Cancer Genome Atlas (TCGA), which included information on clinical characteristics. Moreover, mRNA and protein expression data of CSTF2 were obtained from the Human Protein Atlas (HPA) database. Additionally, CSTF2 mRNA levels were validated in an independent cohort of HNSCC patient tissues and cell lines using real-time PCR. The prognostic significance of CSTF2 was evaluated using Kaplan-Meier survival plots. Additionally, protein-protein interaction networks of CSTF2 were established using the GeneMANIA database, and functional enrichment analysis was performed with Metascape.
Result
The study demonstrated that the CSTF2 gene was significantly amplified, which correlated with elevated mRNA expression. Moreover, independent cohort analysis confirmed that CSTF2 was overexpressed in HNSCC tissues and cell lines compared to non-tumorous tissues and normal cells. In addition, protein levels were markedly higher in HNSCC tissues, and elevated CSTF2 mRNA expression was associated with poorer overall survival. Functional enrichment analysis showed that CSTF2 is involved in regulating oncogenic processes and the progression of HNSCC.
Conclusion
These data indicate that the CSTF2 gene is amplified and overexpressed in HNSCC, indicating that this gene could be a significant prognostic marker and a potential therapeutic target for HNSCC.
目的探讨新发现的n6 -甲基腺苷（m6A）结合蛋白裂解刺激因子亚单位2 （CSTF2）在头颈部鳞状细胞癌（HNSCC）发病机制中的作用。我们还探讨了其扩增驱动的过表达，其预后意义以及其对肿瘤侵袭性的机制贡献。方法使用来自癌症基因组图谱（TCGA）的HNSCC患者数据集，其中包括临床特征信息。此外，从人类蛋白图谱（Human protein Atlas， HPA）数据库中获得CSTF2 mRNA和蛋白的表达数据。此外，使用实时PCR技术在HNSCC患者组织和细胞系的独立队列中验证了CSTF2 mRNA水平。采用Kaplan-Meier生存图评估CSTF2的预后意义。此外，利用GeneMANIA数据库建立CSTF2蛋白-蛋白相互作用网络，并利用metscape进行功能富集分析。结果CSTF2基因显著扩增，与mRNA表达升高相关。此外，独立队列分析证实，与非肿瘤组织和正常细胞相比，CSTF2在HNSCC组织和细胞系中过表达。此外，HNSCC组织中蛋白质水平明显升高，CSTF2 mRNA表达升高与较差的总生存率相关。功能富集分析表明，CSTF2参与调节HNSCC的癌变过程和进展。结论CSTF2基因在HNSCC中存在扩增和过表达，提示该基因可能是HNSCC的重要预后标志物和潜在的治疗靶点。
{"title":"The role of a novel m6A reader CSTF2 amplification and overexpression in head and neck cancer development","authors":"Paramasivam Arumugam , Chandra Pandi , Vijayashree Priyadharsini Jayaseelan","doi":"10.1016/j.humgen.2025.201473","DOIUrl":"10.1016/j.humgen.2025.201473","url":null,"abstract":"<div><h3>Objective</h3><div>This study examines the oncogenic role of cleavage stimulation factor subunit 2 (CSTF2), a newly identified N6-methyladenosine (m6A)-binding protein in the pathogenesis of head and neck squamous cell carcinoma (HNSCC). We also explored its amplification-driven overexpression, its prognostic significance, and its mechanistic contributions to tumor aggressiveness.</div></div><div><h3>Method</h3><div>A dataset of patients with HNSCC was used from the Cancer Genome Atlas (TCGA), which included information on clinical characteristics. Moreover, mRNA and protein expression data of CSTF2 were obtained from the Human Protein Atlas (HPA) database. Additionally, <em>CSTF2</em> mRNA levels were validated in an independent cohort of HNSCC patient tissues and cell lines using real-time PCR. The prognostic significance of <em>CSTF2</em> was evaluated using Kaplan-Meier survival plots. Additionally, protein-protein interaction networks of CSTF2 were established using the GeneMANIA database, and functional enrichment analysis was performed with Metascape.</div></div><div><h3>Result</h3><div>The study demonstrated that the <em>CSTF2</em> gene was significantly amplified, which correlated with elevated mRNA expression. Moreover, independent cohort analysis confirmed that <em>CSTF2</em> was overexpressed in HNSCC tissues and cell lines compared to non-tumorous tissues and normal cells. In addition, protein levels were markedly higher in HNSCC tissues, and elevated <em>CSTF2</em> mRNA expression was associated with poorer overall survival. Functional enrichment analysis showed that CSTF2 is involved in regulating oncogenic processes and the progression of HNSCC.</div></div><div><h3>Conclusion</h3><div>These data indicate that the <em>CSTF2</em> gene is amplified and overexpressed in HNSCC, indicating that this gene could be a significant prognostic marker and a potential therapeutic target for HNSCC.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201473"},"PeriodicalIF":0.7,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-06DOI: 10.1016/j.humgen.2025.201472
Sagy Elzalabany , Ibrahim H. Aboughaleb , Mohamed Hisham Fouad Aref , Tarek Taha , Khaled Amer , Sahar Fawzi , Olfat Shaker
Background and objective
Short Tandem Repeats (STRs) are widely used genetic markers for forensic identification and population genetics due to their high polymorphism. Given Egypt's unique position at the crossroads of Africa, Asia, and Europe, this study aims to analyze the allele frequency distribution of 15 autosomal STR loci in Egyptians and assess their genetic affinities with over 60 other global populations. The objective is to characterize Egypt's genetic profile, evaluate its intra- and inter-regional relationships, and contribute to a broader understanding of global STR clustering.
Methods
Allele frequency data for 15 autosomal STR loci were collected for the Egyptian population and compared with datasets from diverse global populations using Pearson's correlation coefficients, FST genetic distances, and Nei's genetic distance. Hierarchical clustering (UPGMA), allele frequency trajectories (AFTs), and Principal Coordinates Analysis (PCoA) were used to visualize genetic relationships. The findings were contextualized with prior studies of regional genetic structure for completeness and accuracy.
Results
The Egyptian STR profile showed moderate to high correlation (r > 0.85) with Middle Eastern, North African, and Southern European populations. FST and Nei's genetic distance values placed Egypt at a transitional point between Sub-Saharan African and Eurasian clusters. AFT plots revealed several loci with population-specific allele shifts, consistent with historical migration and admixture patterns. Notably, the results aligned with Omran et al.'s finding of genetic divergence between Northern and Southern Egyptians, and supported the tripartite global clustering model described in the 2014 worldwide STR analysis.
Conclusions
Egypt exhibits a unique genetic signature that reflects both African and Eurasian contributions, supporting its role as a genetic bridge population. These findings are valuable for forensic databases, population history, and anthropological studies. Future research should incorporate genome-wide SNP and uniparental marker analyses to further explore Egypt's internal diversity and its broader genetic connections.
背景与目的短串联重复序列（short Tandem Repeats, STRs）因其高多态性而被广泛用于法医鉴定和群体遗传学。鉴于埃及处于非洲、亚洲和欧洲的十字路口的独特位置，本研究旨在分析埃及人15个常染色体STR位点的等位基因频率分布，并评估其与60多个其他全球人群的遗传亲和性。目的是描述埃及的遗传概况，评估其区域内和区域间关系，并有助于更广泛地了解全球STR聚类。方法收集埃及人群15个常染色体STR基因座的等位基因频率数据，并使用Pearson相关系数、FST遗传距离和Nei遗传距离与全球不同人群的数据进行比较。使用分层聚类（UPGMA）、等位基因频率轨迹（AFTs）和主坐标分析（PCoA）来可视化遗传关系。为了完整性和准确性，研究结果与先前的区域遗传结构研究相结合。结果埃及人STR与中东、北非和南欧人群呈中等至高度相关（r > 0.85）。FST和Nei的遗传距离值将埃及置于撒哈拉以南非洲和欧亚集群之间的过渡点。AFT图显示了几个具有群体特异性等位基因转移的位点，与历史迁移和混合模式一致。值得注意的是，这些结果与Omran等人关于埃及北部和南部遗传差异的发现一致，并支持2014年全球STR分析中描述的三方全球聚类模型。结论埃及表现出独特的遗传特征，反映了非洲和欧亚的贡献，支持其作为遗传桥梁群体的作用。这些发现对法医数据库、人口历史和人类学研究都很有价值。未来的研究应结合全基因组SNP和单代标记分析，以进一步探索埃及的内部多样性及其更广泛的遗传联系。
{"title":"Genetic convergence and diversity: A comparative analysis of Egyptian autosomal STR profiles within global populations","authors":"Sagy Elzalabany , Ibrahim H. Aboughaleb , Mohamed Hisham Fouad Aref , Tarek Taha , Khaled Amer , Sahar Fawzi , Olfat Shaker","doi":"10.1016/j.humgen.2025.201472","DOIUrl":"10.1016/j.humgen.2025.201472","url":null,"abstract":"<div><h3>Background and objective</h3><div>Short Tandem Repeats (STRs) are widely used genetic markers for forensic identification and population genetics due to their high polymorphism. Given Egypt's unique position at the crossroads of Africa, Asia, and Europe, this study aims to analyze the allele frequency distribution of 15 autosomal STR loci in Egyptians and assess their genetic affinities with over 60 other global populations. The objective is to characterize Egypt's genetic profile, evaluate its intra- and inter-regional relationships, and contribute to a broader understanding of global STR clustering.</div></div><div><h3>Methods</h3><div>Allele frequency data for 15 autosomal STR loci were collected for the Egyptian population and compared with datasets from diverse global populations using Pearson's correlation coefficients, FST genetic distances, and Nei's genetic distance. Hierarchical clustering (UPGMA), allele frequency trajectories (AFTs), and Principal Coordinates Analysis (PCoA) were used to visualize genetic relationships. The findings were contextualized with prior studies of regional genetic structure for completeness and accuracy.</div></div><div><h3>Results</h3><div>The Egyptian STR profile showed moderate to high correlation (<em>r</em> > 0.85) with Middle Eastern, North African, and Southern European populations. FST and Nei's genetic distance values placed Egypt at a transitional point between Sub-Saharan African and Eurasian clusters. AFT plots revealed several loci with population-specific allele shifts, consistent with historical migration and admixture patterns. Notably, the results aligned with Omran et al.'s finding of genetic divergence between Northern and Southern Egyptians, and supported the tripartite global clustering model described in the 2014 worldwide STR analysis.</div></div><div><h3>Conclusions</h3><div>Egypt exhibits a unique genetic signature that reflects both African and Eurasian contributions, supporting its role as a genetic bridge population. These findings are valuable for forensic databases, population history, and anthropological studies. Future research should incorporate genome-wide SNP and uniparental marker analyses to further explore Egypt's internal diversity and its broader genetic connections.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201472"},"PeriodicalIF":0.7,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hair is among the most frequent types of biological evidence recovered at crime scenes, playing a crucial role in identifying culprits. Often, the recovered hair samples are dyed with various routinely used hair dyes. A survey of 182 individuals showed that the majority (82 %) of individuals dye their hair frequently, at least once a month. Cetearyl alcohol, propylene glycol, and disodium EDTA are the most common ingredients of the commercially available hair dyes. In-silico analysis predicted that the citric acid component of hair dye has the strongest affinity with Taq Polymerase (−6.1 Kcal/mol), followed by ascorbic acid (−5.5 Kcal/mol), resorcinol (−5.0 Kcal/mol), trisodium EDTA (−4.8 Kcal/mol), phosphoric acid (−4.0 Kcal/mol), glycerin and cetyl alcohol (−3.7 Kcal/mol), propylene glycol (−3.5 Kcal/mol), ethanolamine (−3.0 Kcal/mol) and hydrogen peroxide (−2.9 Kcal/mol). Molecular docking studies further revealed that the residues of arginine, threonine, glutamine, lysine, threonine, asparagine, serine, aspartic acid, phenylalanine, leucine, methionine, and tryptophan are the responsible motifs of Taq Polymerase which bind with different hair dye chemical constituents. In a singleplex PCR, the CYCLO gene was amplified only in the presence of cetyl alcohol, glycerin, and ethanolamine. All 23 STR markers were amplified using the Fusion 6C kit in the presence of hair dyes. However, the dye constituents adversely affected the Locus Balance of the STR profiles. Thus, most of the hair dye components act as potential PCR inhibitors by interacting with Taq Polymerase and suitable mitigation strategies should be employed for such forensic biological samples.
{"title":"Assessment of the PCR inhibitory effect of the hair dye constituents and its role in forensic DNA analysis","authors":"Hirak Ranjan Dash , Vaishnavi Gupta , Dnyaneshwar Tanpure , Braja Kishore Mohapatra","doi":"10.1016/j.humgen.2025.201471","DOIUrl":"10.1016/j.humgen.2025.201471","url":null,"abstract":"<div><div>Hair is among the most frequent types of biological evidence recovered at crime scenes, playing a crucial role in identifying culprits. Often, the recovered hair samples are dyed with various routinely used hair dyes. A survey of 182 individuals showed that the majority (82 %) of individuals dye their hair frequently, at least once a month. Cetearyl alcohol, propylene glycol, and disodium EDTA are the most common ingredients of the commercially available hair dyes. <em>In-silico</em> analysis predicted that the citric acid component of hair dye has the strongest affinity with Taq Polymerase (−6.1 Kcal/mol), followed by ascorbic acid (−5.5 Kcal/mol), resorcinol (−5.0 Kcal/mol), trisodium EDTA (−4.8 Kcal/mol), phosphoric acid (−4.0 Kcal/mol), glycerin and cetyl alcohol (−3.7 Kcal/mol), propylene glycol (−3.5 Kcal/mol), ethanolamine (−3.0 Kcal/mol) and hydrogen peroxide (−2.9 Kcal/mol). Molecular docking studies further revealed that the residues of arginine, threonine, glutamine, lysine, threonine, asparagine, serine, aspartic acid, phenylalanine, leucine, methionine, and tryptophan are the responsible motifs of Taq Polymerase which bind with different hair dye chemical constituents. In a singleplex PCR, the <em>CYCLO</em> gene was amplified only in the presence of cetyl alcohol, glycerin, and ethanolamine. All 23 STR markers were amplified using the Fusion 6C kit in the presence of hair dyes. However, the dye constituents adversely affected the Locus Balance of the STR profiles. Thus, most of the hair dye components act as potential PCR inhibitors by interacting with Taq Polymerase and suitable mitigation strategies should be employed for such forensic biological samples.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201471"},"PeriodicalIF":0.7,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144917761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Colorectal cancer (CRC) is a major global health challenge, with long non-coding RNAs (lncRNAs) gaining attention as potential diagnostic biomarkers. This study aimed to experimentally validate bioinformatics findings on the expression patterns of maternally expressed gene 3 (MEG3) and LINC01611 in CRC patients from a specific ethnic population while considering associated risk factors. This in vitro study initially recruited 50 patients from a single ethnic group, with 48 completing the analysis after the exclusion of two samples. Two lncRNAs, MEG3 and LINC01611, were selected using Gene Expression Omnibus (GEO) microarray data and identified via R/BioConductor. Paired tissue samples (tumor and adjacent margins) were collected during surgery, and RNAs were extracted. Demographic and clinical data of patients were recorded, and gene expression was analyzed using quantitative real-time PCR (qPCR), with GAPDH as the internal control. Data analysis was performed using GraphPad Prism and SPSS software, with the significance level set at P < 0.05. The mean age of the patients was 59.5 ± 3.53 years, with 58.3 % (n = 28) being male, and 37.5 % of the patients had a history of smoking. The majority of patients had poorly differentiated (41.7 %) and stage II tumor (43.8 %), with lymph node metastasis commonly observed (60.4 %). The Wilcoxon signed-rank test revealed significant downregulation of MEG3 (32.396 fold change)and LINC01611(38.923 fold change) in tumor tissues compared to adjacent margins. A family history of CRC was associated with higher expression levels of MEG3 (1.48-fold, P = 0.038) and LINC01611 (1.03-fold, P = 0.007) in both tumor and margin tissues. Multivariable regression analysis demonstrated that lncRNAs had a significant association with tumor differentiation (P < 0.05), while other variables showed no statistically significant association (P > 0.05). Also, positive correlations were observed between MEG3 and LINC01611 expression levels in tumor (r = 0.649, P < 0.001) and margin (r = 0.424, P = 0.003) tissues. The significant downregulation of MEG3 and LINC01611 in tumor tissues compared to adjacent margin tissues highlights their potential role as tumor suppressors in CRC. These findings support further investigation into these lncRNAs as diagnostic biomarkers.
{"title":"Altered expression patterns of lncRNA MEG3 and LINC01611 in patients with colorectal cancer","authors":"Niloofar Faraji , Mohammad Almasi , Majid Mirmazloumi , Nasim Padasht , Sahand Sadat Mansouri , Fatemeh Ghaderibarmi , Haniyeh Royatpour , Fatemeh Modaresi , Kourosh Kazempour Samak , Fahimeh Abedini Bajgiran , Tahereh Zeinali , Narges Eslami , Dariush Shanehbandi , Ali Salehzadeh","doi":"10.1016/j.humgen.2025.201470","DOIUrl":"10.1016/j.humgen.2025.201470","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is a major global health challenge, with long non-coding RNAs (lncRNAs) gaining attention as potential diagnostic biomarkers. This study aimed to experimentally validate bioinformatics findings on the expression patterns of maternally expressed gene 3 (MEG3) and LINC01611 in CRC patients from a specific ethnic population while considering associated risk factors. This in vitro study initially recruited 50 patients from a single ethnic group, with 48 completing the analysis after the exclusion of two samples. Two lncRNAs, MEG3 and LINC01611, were selected using Gene Expression Omnibus (GEO) microarray data and identified via R/BioConductor. Paired tissue samples (tumor and adjacent margins) were collected during surgery, and RNAs were extracted. Demographic and clinical data of patients were recorded, and gene expression was analyzed using quantitative real-time PCR (qPCR), with GAPDH as the internal control. Data analysis was performed using GraphPad Prism and SPSS software, with the significance level set at <em>P</em> < 0.05. The mean age of the patients was 59.5 ± 3.53 years, with 58.3 % (<em>n</em> = 28) being male, and 37.5 % of the patients had a history of smoking. The majority of patients had poorly differentiated (41.7 %) and stage II tumor (43.8 %), with lymph node metastasis commonly observed (60.4 %). The Wilcoxon signed-rank test revealed significant downregulation of MEG3 (32.396 fold change)and LINC01611(38.923 fold change) in tumor tissues compared to adjacent margins. A family history of CRC was associated with higher expression levels of MEG3 (1.48-fold, <em>P</em> = 0.038) and LINC01611 (1.03-fold, <em>P</em> = 0.007) in both tumor and margin tissues. Multivariable regression analysis demonstrated that lncRNAs had a significant association with tumor differentiation (<em>P</em> < 0.05), while other variables showed no statistically significant association (<em>P</em> > 0.05). Also, positive correlations were observed between MEG3 and LINC01611 expression levels in tumor (<em>r</em> = 0.649, <em>P</em> < 0.001) and margin (<em>r</em> = 0.424, <em>P</em> = 0.003) tissues. The significant downregulation of MEG3 and LINC01611 in tumor tissues compared to adjacent margin tissues highlights their potential role as tumor suppressors in CRC. These findings support further investigation into these lncRNAs as diagnostic biomarkers.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201470"},"PeriodicalIF":0.7,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144931728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Breast cancer (BC) is the most prevalent and lethal cancer among women worldwide. Overexpression of the MUC1 gene is observed in approximately 40 % of BC cases. Additionally, mucin-1-derived antigens are recognized as significant serum biomarkers for BC. Identifying genetic regulators of MUC1 may reveal novel pathways for managing and treating BC. This study investigates the regulatory relationship between circMYO9B, hsa-miR-3529-5p, and MUC1 expression.
Methods
We utilized circAtlas, CircNet, and miRWalk databases to predict interactions between circMYO9B and hsa-miR-3529-5p and between hsa-miR-3529-5p and MUC1. RNA22 and RNAhybrid-BiBiServe2 confirmed an 82 % high-binding affinity between hsa-miR-3529-5p and MUC1. Experimental validation included RT-qPCR to quantify circMYO9B, hsa-miR-3529-5p, and MUC1 expression levels. Functional assays were performed by constructing plasmids for circMYO9B, hsa-miR-3529-5p, and MUC1, transfecting them into HEK293T cells, and conducting dual luciferase reporter assays.
Result
Our results demonstrate that circMYO9B interacts directly with hsa-miR-3529-5p, functioning as a sponge to regulate MUC1 expression in BC. This regulatory axis involving circMYO9B and hsa-miR-3529-5p provides insights into the molecular mechanisms underlying MUC1 dysregulation. MUC1, a key BC gene and marker, may be influenced by this interaction, emphasizing its potential as a target for therapeutic and diagnostic strategies. Subsequent cell viability assays confirmed that overexpression of miR-3529-5p significantly reduced MCF7 cell survival, suggesting an increase in apoptosis.
Discussion
This study provides valuable insights into the molecular mechanisms underlying MUC1 regulation and emphasizes the importance of miR-3529 and circMYO9B in modulating MUC1 expression, which may have implications for targeted therapies and diagnostic strategies in breast cancer.
{"title":"Regulatory Axis of circMYO9B and hsa-miR-3529-5p in modulating the breast Cancer biomarker MUC1","authors":"Farnaz Nourmohammadian Dehkordi , Fatemeh Chaharlang , Niosha Yahyavi , Sadaf Gilanian , Anosha Yahyavi kalkhoran , Mohamadali Naderi , Maryam Yousefi , Nasrin Fattahi Dolatabadi","doi":"10.1016/j.humgen.2025.201468","DOIUrl":"10.1016/j.humgen.2025.201468","url":null,"abstract":"<div><h3>Purpose</h3><div>Breast cancer (BC) is the most prevalent and lethal cancer among women worldwide. Overexpression of the MUC1 gene is observed in approximately 40 % of BC cases. Additionally, mucin-1-derived antigens are recognized as significant serum biomarkers for BC. Identifying genetic regulators of MUC1 may reveal novel pathways for managing and treating BC. This study investigates the regulatory relationship between circMYO9B, hsa-miR-3529-5p, and MUC1 expression.</div></div><div><h3>Methods</h3><div>We utilized circAtlas, CircNet, and miRWalk databases to predict interactions between circMYO9B and hsa-miR-3529-5p and between hsa-miR-3529-5p and MUC1. RNA22 and RNAhybrid-BiBiServe2 confirmed an 82 % high-binding affinity between hsa-miR-3529-5p and MUC1. Experimental validation included RT-qPCR to quantify circMYO9B, hsa-miR-3529-5p, and MUC1 expression levels. Functional assays were performed by constructing plasmids for circMYO9B, hsa-miR-3529-5p, and MUC1, transfecting them into HEK293T cells, and conducting dual luciferase reporter assays.</div></div><div><h3>Result</h3><div>Our results demonstrate that circMYO9B interacts directly with hsa-miR-3529-5p, functioning as a sponge to regulate MUC1 expression in BC. This regulatory axis involving circMYO9B and hsa-miR-3529-5p provides insights into the molecular mechanisms underlying MUC1 dysregulation. MUC1, a key BC gene and marker, may be influenced by this interaction, emphasizing its potential as a target for therapeutic and diagnostic strategies. Subsequent cell viability assays confirmed that overexpression of miR-3529-5p significantly reduced MCF7 cell survival, suggesting an increase in apoptosis.</div></div><div><h3>Discussion</h3><div>This study provides valuable insights into the molecular mechanisms underlying MUC1 regulation and emphasizes the importance of miR-3529 and circMYO9B in modulating MUC1 expression, which may have implications for targeted therapies and diagnostic strategies in breast cancer.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201468"},"PeriodicalIF":0.7,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Copy number variations (CNVs) have been identified as critical contributors to head and neck squamous cell carcinoma (HNSCC) pathogenesis. Multi-omics analyses offer a comprehensive understanding of its underlying genetic complexities. Therefore, this study aims to examine the CNV-driven long non-coding RNAs (lncRNAs) influencing global regulatory triplet networks (lncRNA–miRNA–mRNA) in HPV-positive and HPV-negative HNSCC subtypes. Differential expression of miRNAs, mRNAs, and CNV-associated lncRNAs were identified using TCGA-HNSCC data. Subsequently, target prediction analyses enabled the construction of CNV-driven global triplet networks specific to HPV status. Gene Ontology (GO) analysis revealed that mRNAs in HPV-positive HNSCC were enriched in cancer-associated processes such as cell proliferation and extracellular matrix (ECM) organization. In contrast, those in HPV-negative HNSCC were primarily enriched in tissue remodeling, development, and cancer progression. KEGG pathway enrichment further supported these findings. The relationship between the CNV of lncRNA MCCC1-AS1 and its expression has revealed that there was no correlation between them in the HPV-positive HNSCC, while in the HPV-negative HNSCC, the gene expression of lncRNA MCCC1-AS1 was correlated with the CNV status. Survival analysis disclosed that the patient with a copy number gain of MCCC1-AS1 was associated with a shorter survival time, suggesting its potential as a prognostic biomarker. These findings highlight the significance of CNV-driven lncRNAs in the molecular landscape of HNSCC and suggest that MCCC1-AS1 may serve as a promising target for further investigation in diagnostic and therapeutic strategies.
{"title":"A systems biology approach to uncover CNV-driven lncRNA regulatory networks in HPV-associated head and neck squamous cell carcinoma","authors":"Avantika Agrawal, Pubali Bhattacharjee, Swapnil Kumar, Vaibhav Vindal","doi":"10.1016/j.humgen.2025.201469","DOIUrl":"10.1016/j.humgen.2025.201469","url":null,"abstract":"<div><div>Copy number variations (CNVs) have been identified as critical contributors to head and neck squamous cell carcinoma (HNSCC) pathogenesis. Multi-omics analyses offer a comprehensive understanding of its underlying genetic complexities. Therefore, this study aims to examine the CNV-driven long non-coding RNAs (lncRNAs) influencing global regulatory triplet networks (lncRNA–miRNA–mRNA) in HPV-positive and HPV-negative HNSCC subtypes. Differential expression of miRNAs, mRNAs, and CNV-associated lncRNAs were identified using TCGA-HNSCC data. Subsequently, target prediction analyses enabled the construction of CNV-driven global triplet networks specific to HPV status. Gene Ontology (GO) analysis revealed that mRNAs in HPV-positive HNSCC were enriched in cancer-associated processes such as cell proliferation and extracellular matrix (ECM) organization. In contrast, those in HPV-negative HNSCC were primarily enriched in tissue remodeling, development, and cancer progression. KEGG pathway enrichment further supported these findings. The relationship between the CNV of lncRNA MCCC1-AS1 and its expression has revealed that there was no correlation between them in the HPV-positive HNSCC, while in the HPV-negative HNSCC, the gene expression of lncRNA MCCC1-AS1 was correlated with the CNV status. Survival analysis disclosed that the patient with a copy number gain of MCCC1-AS1 was associated with a shorter survival time, suggesting its potential as a prognostic biomarker. These findings highlight the significance of CNV-driven lncRNAs in the molecular landscape of HNSCC and suggest that MCCC1-AS1 may serve as a promising target for further investigation in diagnostic and therapeutic strategies.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201469"},"PeriodicalIF":0.7,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144912332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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