Annals of Human Genetics最新文献

{"title":"A Novel Variant of STAG1 Gene and Literature Review.","authors":"Meihua Xie, Liyun Xie, Jianlong Zhuang, Hening Li, Hongxia Zhou, Xiaojuan Yue","doi":"10.1111/ahg.70023","DOIUrl":"https://doi.org/10.1111/ahg.70023","url":null,"abstract":"<p><strong>Objective: </strong>To explore the clinical presentation and genetic etiology of a child with intellectual disability, speech developmental delay, learning difficulties, behavioral stereotype, and obsessive-compulsive disorder, and to identify new variants.</p><p><strong>Methods and results: </strong>In this study, Karyotype and copy number variant sequencing (CNV-seq) were performed to detect chromosome abnormalities in this family. The whole exome sequencing (WES) was performed to investigate additional genetic variants in this family. Minigene array was used to verify whether the novel variant c.1027-2A>G really affected the splicing of STAG1 gene. Chromosomal karyotyping and CNV-seq analysis did not reveal any chromosomal abnormalities. The WES result demonstrated a de novo NM_005862.3:c.1027-2A>G variant in STAG1 gene in the patient. This splicing variant was classified as likely pathogenic based on ACMG/AMP guidelines. Minigene array results showed that the variant could result in the appearance of premature termination codon.</p><p><strong>Conclusion: </strong>Our study identified a novel pathogenic locus, c.1027-2A>G, associated with Intellectual developmental disorder, autosomal dominant 47 (MRD47).</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of the Main Human Genetic Variants Related to Resistance to Malaria in a Population of the Colombian Pacific Coast.","authors":"Diana Carolina Ortega, María Paula Arango, Sergio Cañón, Heiber Cárdenas, Ranulfo González, Guillermo Barreto","doi":"10.1111/ahg.70022","DOIUrl":"https://doi.org/10.1111/ahg.70022","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to determine the prevalence of Duffy, HbS, HbC, G6PD, and β-thalassemia variants through molecular characterisation in a representative sample of the population from the urban area of Buenaventura, Colombia.</p><p><strong>Material and methods: </strong>A total of 819 individuals were randomly selected from 12 communities within the city. Molecular analysis was performed using PCR-RFLP and allele-specific PCR. Data were analysed using descriptive statistics, tests of independence, and regression analysis.</p><p><strong>Results: </strong>Frequencies of 3.1%, 2.2%, 72.2%, 2.1%, 2.8%, and 11% were found for the resistance alleles HbS, HbC, Duffy, β-thalassemia-29, β-thalassemia-88 and G6PD, respectively. In addition, adolescents and young adults (13 to 26 years) presented the highest proportion of resistance genotypes. Likewise, the communities of the insular zone of Buenaventura had the highest proportion of resistance genotypes.</p><p><strong>Conclusions: </strong>These findings should be considered by public health and disease prevention authorities, as they highlight specific age groups and communities that may be more susceptible to malaria infection. They also identify groups that may contribute to the persistence and potential increase in the prevalence of haemoglobinopathies in the population over time.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Centenary Special Issue of the Annals of Human Genetics","authors":"John Armour,&nbsp;Rosemary Ekong","doi":"10.1111/ahg.70018","DOIUrl":"10.1111/ahg.70018","url":null,"abstract":"","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"89 5","pages":"239-240"},"PeriodicalIF":1.2,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Determinants of Response to Neoadjuvant Chemoradiotherapy in Rectal Cancer Identified by Whole Exome Sequencing.","authors":"Jelena Peric, Sandra Dragicevic, Marko Miladinov, Aleksandra Djikic Rom, Jasna Bjelanovic, Jelena Kovac, Jovana Despotovic, Tamara Babic, Jelena Ljubicic, Dunja Pavlovic, Jovana Rosic Stojkovic, Ivan Dimitrijevic, Goran Barisic, Velimir Markovic, Aleksandra Nikolic","doi":"10.1111/ahg.70019","DOIUrl":"https://doi.org/10.1111/ahg.70019","url":null,"abstract":"<p><strong>Background: </strong>Neoadjuvant chemoradiotherapy (nCRT) is essential for treating locally advanced rectal cancer (LARC), however response to nCRT varies, and reliable predictors are lacking.</p><p><strong>Methods: </strong>This study used whole exome sequencing analysis to investigate genetic differences between tumors highly responsive and non-responsive to nCRT. Five patients with good response and two patients without response to nCRT were used as a discovery set.</p><p><strong>Results: </strong>The analysis identified 15 InDels and 202 non-synonymous SNVs exclusively present in tumors of non-responders, mainly in genes regulating the cell cycle, adhesion, and migration. In contrast, 9 InDels and 122 non-synonymous SNVs were exclusively present in tumors of good responders, primarily in extracellular matrix remodeling and immunity-related genes. Six variants in transmembrane transporter genes were selected as candidate biomarkers and validated in 33 LARC patients.</p><p><strong>Conclusion: </strong>The results suggest that SLC16A6 rs7222013 and SLC25A2 rs3749780 may serve as potential predictors of poor nCRT response in LARC patients.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polygenic Risk Score for Cancer in African Population: A Systematic Review.","authors":"Wafaa M Rashed, Olagunju Abdulrahmon A","doi":"10.1111/ahg.70016","DOIUrl":"https://doi.org/10.1111/ahg.70016","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of this systematic review is to identify all genome-wide association study (GWAS)-based polygenic risk score (PRS) studies (with different PRS approaches) reported in African ancestry populations diagnosed with any type of cancer. Additionally, this review assessed the role of PRS in advancing precision medicine through its clinical utility across different cancer types in African populations.</p><p><strong>Methods: </strong>We searched PubMed from January 2009 to April 2023 and included GWAS-based PRS studies for cancer patients of African genetic ancestry.</p><p><strong>Results: </strong>Among the 33 eligible studies, prostate cancer and breast cancer were the most common types in adults, whereas only one publication reported the risk association of neuroblastoma (a pediatric cancer). The most common PRS approach used was ancestry-specific PRS. Clinical utility of the calculated PRS varies across cancer types, with inconsistent results. Our systematic review found a limited number of PRS studies on cancer patients (adult and pediatric) of African ancestry, and these studies showed less clinical utility compared to those conducted in European ancestry populations.</p><p><strong>Conclusion: </strong>To make PRS clinically actionable for African ancestry populations, it is crucial to increase the number of large-scale, population-specific GWAS, improve the representation of African-ancestry cohorts, and refine PRS models to better reflect the genetic diversity within African populations.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The History of the Panmictic Population Concept and Its Legacy in Contemporary Population Genetics","authors":"Andy Walton,&nbsp;Alex Aylward,&nbsp;Mark G. Thomas,&nbsp;Adam Rutherford","doi":"10.1111/ahg.70015","DOIUrl":"10.1111/ahg.70015","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> ABSTRACT</h3>\u0000 \u0000 <p>The panmictic population concept is at the heart of population, evolutionary and conservation genetics. However, in nature, true panmictic populations are vanishingly rare. As an idea conceived for modelling evolutionary dynamics, it has been thought that the assumption of panmixia was formalised during the development of the Modern Synthesis. Here, we show that while the idea's longevity is almost certainly due to its mathematical convenience, it became embedded in evolutionary thought much earlier, initially as a way to reconcile long-standing essentialist ideas with the advent of Darwin's theories. Though the principles of essentialism and reversion have been largely rejected, these ideas persist in shaping assumptions made about populations in contemporary genetics research, including how they are conceptualised and sampled. This legacy has important implications for the interpretation of genomic findings in human evolution, conservation and medicine. From an evaluation of this history and its legacy, we contend that while the panmictic population concept has been, and continues to be useful, with the generation of terabytes of genomic data in the 21st century, its utility is likely to diminish as the need for continuous space models grows.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"89 5","pages":"274-284"},"PeriodicalIF":1.2,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.70015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the LOXHD1 Mutational Spectrum: A North Indian Case of ARNSHL.","authors":"Pratiksha Chheda, Tavisha Dama, Tanmay Deshpande","doi":"10.1111/ahg.70017","DOIUrl":"https://doi.org/10.1111/ahg.70017","url":null,"abstract":"","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal Relationships Between Gastroesophageal Reflux Disease and Myocardial Infarction: Insights From Univariable and Multivariable Mendelian Randomization Analyses.","authors":"Xiaoya Zheng, Teng Hu, Tianxiang Fang, Pengpeng Su, Yingsong Wang, Ning Huangfu","doi":"10.1111/ahg.70012","DOIUrl":"https://doi.org/10.1111/ahg.70012","url":null,"abstract":"<p><strong>Background: </strong>Observational studies have indicated that gastroesophageal reflux disease (GERD) is connected to myocardial infarction (MI). Nonetheless, the question of causality in these relationships remains unresolved, given the potential influence of confounding variables. The aim is to study the causal link of GERD with MI and determine whether MI factors have any mediation effects in the causative chain.</p><p><strong>Methods: </strong>GERD (129,080 cases and 473,524 controls) and MI (831,000 individuals) were obtained from the latest genome-wide association study summary-level data. Two-sample Mendelian randomization (MR) analyses were performed to assess the associations of genetically predicted GERD with MI risk. After adjusting for several confounders, multivariable MR was employed to determine the independent impacts of GERD on MI risk. Two-step MR analyses were carried out to investigate the mediating impacts of these modifiable factors in the relationships between GERD and MI.</p><p><strong>Results: </strong>The current univariable MR analysis indicated that GERD was connected to MI (odds ratio [OR] = 1.61; 95% confidence interval [CI]: 1.48-1.76; p = 1.01 × 10^-26), whereas this correlation remained after controlling for body mass index, cigarettes per day, and alcohol consumption. Two-step MR found that several MI-associated risk factors mediated the associations between GERD and MI, with hypertension (mediation proportion: 14.4%) and type-2 diabetes mellitus (12.0%) exhibiting higher mediation proportions among the mediating networks.</p><p><strong>Conclusion: </strong>This study identifies modifiable cardiovascular risk factors that may mediate the GERD-MI association, with hypertension (14.4%) and T2DM (12.0%) identified as the predominant modifiable mediators. These findings highlight the clinical importance of integrated cardiometabolic monitoring in GERD patients, suggesting that targeted management of blood pressure and glycemic control may mitigate MI risk in GERD populations.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":" ","pages":"e70012"},"PeriodicalIF":1.2,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the Effectiveness of Forensic Application and Population Genetic Diversity Using a Multi-InDel System in Chinese Hezhou and Southern Shaanxi Han Populations.","authors":"Xi Wang, Qiong Lan, Yifeng Lin, Xi Yuan, Shuyan Mei, Fanzhang Lei, Bonan Dong, Ming Zhao, Meiming Cai, Chunmei Shen, Bofeng Zhu","doi":"10.1111/ahg.70001","DOIUrl":"https://doi.org/10.1111/ahg.70001","url":null,"abstract":"<p><strong>Background: </strong>Multi-insertion/deletion (multi-InDel) markers have greater potential in forensic genetics than InDel, and their efficacy in paternity testing, individual identification, DNA mixture detection, and ancestry inference remains to be explored.</p><p><strong>Material and method: </strong>We designed an efficient and robust system consisting of 41 multi-InDels to evaluate its efficacy in forensic applications in Chinese Hezhou Han (HZH) and Southern Shaanxi Han (SSH) populations and explore the genetic relationships among the SSH, HZH, and 26 reference populations.</p><p><strong>Results and conclusions: </strong>The obtained results showed that most of the 41 multi-InDels had relatively high genetic variations. The cumulative power of discrimination and probability of exclusion values of 40 multi-InDels (except MI38) in HZH and SSH populations both exceeded 1 - e^-25 and 1 - e^-6, respectively. The genetic compositions of HZH and SSH populations were similar to those of East Asian populations, and the multi-InDel system could well distinguish East Asians, Africans, and Europeans. These results indicated that the multi-InDel system can serve as an effective tool to provide important clue for the forensic practical application and also to better analyze the genetic background of Chinese Han population.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":" ","pages":"e70001"},"PeriodicalIF":1.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Genetics of Acne","authors":"Maurice A. M. Van Steensel","doi":"10.1111/ahg.70014","DOIUrl":"10.1111/ahg.70014","url":null,"abstract":"<p>This review addresses the genetics of acne vulgaris, the most common skin disease. It is characterized by the presence of comedones (blackheads), papules, and pustules. The condition is associated with sebaceous glands in the face and chest, which produce an oily substance called sebum. In developed nations, acne affects over 80% of adolescents. Mild disease usually resolves spontaneously. More severe acne can leave permanent, disfiguring scarring and strongly affects quality of life. In those cases, medical intervention is warranted. To date, antibiotics and retinoids (synthetic vitamin A derivatives) are the mainstays of treatment. Depending on the severity of the condition, these drugs may be administered either topically or systemically.</p><p>Whilst generally effective, they do come with significant drawbacks. Antibiotic use for treating acne is contributing to antimicrobial resistance. In addition, indiscriminate eradication of the skin microbiome negatively impacts skin health. Retinoids are teratogenic and have other undesirable side effects, such as skin irritation and increased UV sensitivity. Thus, there is a clear need for effective interventions that target the underlying disease mechanism, minimizing side effects.</p><p>Rapid progress has recently been made in understanding the mechanisms underlying acne. For decades, it was assumed that blackhead formation results from the accumulation of sebum in the hair follicle opening, due to increased sebum production at the onset of puberty. Subsequent colonization by the commensal bacterium <i>Cutibacterium acnes</i> then was thought to cause inflammation. It was also postulated that this micro-organism could induce blackheads. There are, however, several problems with this supposed sequence of events, not the least of which is that it doesn't explain how retinoids work, or why sebaceous glands associated with blackheads are atrophic and hence produce less sebum, not more.</p><p>Both GWAS and single gene disorders unequivocally indicate stem/progenitor cell maintenance and cellular migration as the most important processes in the pathogenesis of acne. Together with insights from mouse models, this new perspective is transforming the way we think about acne and its treatment.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"89 5","pages":"333-341"},"PeriodicalIF":1.2,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.70014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}