Human Genetics最新文献

Most males in modern Poland carry Y-chromosomal lineages from clades that have recently expanded over Central, Eastern and South-Eastern Europe. 现代波兰的大多数男性携带的y染色体谱系来自最近在中欧、东欧和东南欧扩展的分支。

IF 3.6 2区生物学

Human Genetics Pub Date : 2025-10-06 DOI: 10.1007/s00439-025-02781-7

Michał Milewski, Mateusz Dawidziuk

{"title":"Most males in modern Poland carry Y-chromosomal lineages from clades that have recently expanded over Central, Eastern and South-Eastern Europe.","authors":"Michał Milewski, Mateusz Dawidziuk","doi":"10.1007/s00439-025-02781-7","DOIUrl":"https://doi.org/10.1007/s00439-025-02781-7","url":null,"abstract":"Previous studies on Y-chromosomal haplogroup diversity in Poland have been focused mainly on macro-haplogroups. Consequently, younger subclades have rarely been explored to elucidate the relatively recent history of the Polish population. Here we present the results of deep genotyping of 598 chromosome Y sequences from modern Poland and demonstrate that about 60% of Polish males can be assigned to subhaplogroups that are both relatively young and widely distributed among different Slavic populations, thus supporting the scenario in which Early Slavic mass migration and territorial expansion took place in the first millennium of the common era. While most of those young Slavic-associated subclades are part of haplogroup R1a, other haplogroups, including I2a, R1b and E1b, are also represented by specific subclades, which together may constitute an important clue when trying to identify the location of the Proto-Slavic homeland based on ancient DNA data. Additionally, we have identified two specifically Polish subclades (I-Y6343 and R-Z17913, from haplogroups I1a and R1b, respectively) that likely descend from Late Ancient or Early Medieval founders representing the local Pre-Slavic population of the Roman period.","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232362","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}

引用次数: 0

Molecular features of AHDC1: insights into an overlooked gene with broad functional potential. AHDC1的分子特征：一个被忽视的具有广泛功能潜力的基因。

IF 3.6 2区生物学

Human Genetics Pub Date : 2025-10-01 Epub Date: 2025-08-22 DOI: 10.1007/s00439-025-02765-7

Silvana Bochicchio, Aurora Mazzetti, Lorenzo Graziani, Gian Gaetano Tartaglia, Stefano Gustincich, Remo Sanges

{"title":"Molecular features of AHDC1: insights into an overlooked gene with broad functional potential.","authors":"Silvana Bochicchio, Aurora Mazzetti, Lorenzo Graziani, Gian Gaetano Tartaglia, Stefano Gustincich, Remo Sanges","doi":"10.1007/s00439-025-02765-7","DOIUrl":"10.1007/s00439-025-02765-7","url":null,"abstract":"Despite two decades since the completion of the human genome, many genes remain poorly understood, with their functions largely unknown. Among these, AHDC1 stands out as a top-ranking gene in the SFARI database due to its role in the rare and likely underestimated neurodevelopmental disorder, Xia-Gibbs syndrome (XIGIS). First identified in 2014 by Prof. Richard A. Gibbs and his team at Baylor College of Medicine, AHDC1 has historically been understudied. Until July 2023, it was classified as a Tdark gene in the Pharos database, reflecting minimal knowledge of its biological function and the lack of molecular tools for its investigation. However, interest in AHDC1 has grown significantly recently as researchers have strived to uncover the mechanisms underlying XIGIS-associated phenotypes. Recognizing these advances, the Pharos database reclassified AHDC1 as a Tbio gene in 2023, acknowledging its rising significance and the expanding body of research surrounding it. This review consolidates the latest findings on AHDC1, providing an in-depth examination of its genetic structure, regulatory mechanisms, and protein functions while exploring its potential roles in nervous system development and beyond. By compiling existing literature and integrating publicly available data, this review aims to illuminate the broader biological relevance of AHDC1 and its implications for human health and disease.","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":" ","pages":"901-916"},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952127","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}

引用次数: 0

Genetic burden and multidimensional predictors in prenatal diagnosis of fetal congenital diaphragmatic hernia. 胎儿先天性膈疝产前诊断的遗传负担和多维预测因素。

IF 3.6 2区生物学

Human Genetics Pub Date : 2025-10-01 Epub Date: 2025-09-06 DOI: 10.1007/s00439-025-02777-3

Ruibin Huang, Fang Fu, Shanshan Mei, Liyuan Liu, Wei Zhong, Jin Han, Qiuxia Yu, Hang Zhou, Chunling Ma, Li Zhen, Min Pan, Qiong Deng, Jianqin Lu, Xinyi Zhao, Na Zhang, Fei Guo, Huanyi Chen, Xinyue Tan, Fucheng Li, Dongzhi Li, Ru Li, Can Liao

{"title":"Genetic burden and multidimensional predictors in prenatal diagnosis of fetal congenital diaphragmatic hernia.","authors":"Ruibin Huang, Fang Fu, Shanshan Mei, Liyuan Liu, Wei Zhong, Jin Han, Qiuxia Yu, Hang Zhou, Chunling Ma, Li Zhen, Min Pan, Qiong Deng, Jianqin Lu, Xinyi Zhao, Na Zhang, Fei Guo, Huanyi Chen, Xinyue Tan, Fucheng Li, Dongzhi Li, Ru Li, Can Liao","doi":"10.1007/s00439-025-02777-3","DOIUrl":"10.1007/s00439-025-02777-3","url":null,"abstract":"This study aims to assess the genetic burden of fetal congenital diaphragmatic hernia (CDH) and identify prenatal, perinatal, and postnatal predictors to improve early diagnosis, monitoring, and intervention. This study included 130 CDH fetuses who underwent invasive prenatal diagnosis, with fetal prognosis evaluated using imaging parameters such as observed-to-expected lung-to-head ratio (o/e LHR), observed-to-expected total lung volume (o/e TLV), and percent predicted lung volume (PPLV). Clinical outcomes included neonatal outcomes, extracorporeal membrane oxygenation (ECMO) requirement, and post-neonatal prognosis. Logistic regression and receiver operating characteristic (ROC) curve analyses were used to evaluate prognostic indicators and construct predictive models. Chromosomal microarray analysis (CMA) and exome sequencing (ES) yielded diagnostic rates of 7.7% and 8.7%, respectively, identifying a wide spectrum of pathogenic variants and highlighting the genetic heterogeneity of CDH. Among imaging parameters, o/e LHR, o/e TLV, and PPLV were significantly associated with neonatal outcomes, ECMO requirement, and post-neonatal prognosis. Multivariable models incorporating these parameters achieved high predictive accuracy (AUCs > 0.85), with the neonatal outcomes model reaching an AUC of 0.929, sensitivity of 93.2%, and specificity of 78.6%. By integrating genetic, imaging and clinical outcome data, this study identified CMA and ES as key tools for detecting genetic burden in CDH fetuses, and confirmed o/e LHR, o/e TLV, PPLV, and liver herniation as reliable prognostic indicators. Multivariable models based on these parameters showed strong predictive performance. A combined genetic-imaging approach is recommended to support individualized risk assessment and guide perinatal management.","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":" ","pages":"1035-1050"},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006033","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}

引用次数: 0

Direct connexin-26 interactions with membrane proteins functionally relevant to the cochlea. 直接连接蛋白26与耳蜗功能相关的膜蛋白相互作用。

IF 3.6 2区生物学

Human Genetics Pub Date : 2025-10-01 Epub Date: 2025-08-13 DOI: 10.1007/s00439-025-02769-3

Jennifer Costa Leoncio, Ana Carla Batissoco, Thiago Geronimo Pires Alegria, Fernando Gomes, Luis Eduardo Soares Netto, Regina Célia Mingroni-Netto, Luciana Amaral Haddad

{"title":"Direct connexin-26 interactions with membrane proteins functionally relevant to the cochlea.","authors":"Jennifer Costa Leoncio, Ana Carla Batissoco, Thiago Geronimo Pires Alegria, Fernando Gomes, Luis Eduardo Soares Netto, Regina Célia Mingroni-Netto, Luciana Amaral Haddad","doi":"10.1007/s00439-025-02769-3","DOIUrl":"10.1007/s00439-025-02769-3","url":null,"abstract":"Connexin 26, the protein encoded by the GJB2 (Gap junction protein beta 2) gene, is expressed in different tissues, including the cochlea and skin. Pathogenic DNA alterations in GJB2 cause autosomal recessive nonsyndromic hearing loss, whereas some GJB2 variants may lead to deafness-associated skin disorders. Genes encoding proteins of the Connexin26 molecular complex may fit as candidates to explain genetic hearing loss of yet unknown etiology. In search for Connexin26 direct protein partners, 120 million clones of a human fetal brain cDNA library were screened for interaction with full-length Cx26 in a membrane yeast two-hybrid assay. Each Connexin26-interacting protein was submitted to a pipeline of in-silico characterization yielding a total of 40 direct interactors. It was disclosed that the mouse Gjb2 gene orthologue is coexpressed with 38 (95%) and 28 (70%) of the genes encoding Connexin26 interactors, respectively in specific cochlea cell types and embryonic keratinocytes. Interactors expressed in the organ of Corti supporting cells are significantly enriched in the gene ontology class of proteins with transporter activity (N = 10; 26%), seven of which are ion transporters. Nine interactor-encoding genes are either associated with deafness and/or skin disorders or have chromosomal mapping overlapping non-syndromic hearing loss-related loci. Altogether, the Connexin26 membrane interaction network highlights proteins with biological relevance to the physiology of cochlea and skin.","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":" ","pages":"983-1000"},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834980","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}

引用次数: 0

The emerging sequence grammar of 3D genome organisation. 新兴的三维基因组组织序列语法。

IF 3.6 2区生物学

Human Genetics Pub Date : 2025-10-01 Epub Date: 2025-08-25 DOI: 10.1007/s00439-025-02772-8

Liezel Tamon, James Ashford, Matthew Nicholls, Marella F T R de Bruijn, Aleksandr B Sahakyan

引用次数: 0

uAUG-creating variant in the LDLR gene causes mild Familial hypercholesterolemia. LDLR基因中产生uag的变异导致轻度家族性高胆固醇血症。

IF 3.6 2区生物学

Human Genetics Pub Date : 2025-10-01 Epub Date: 2025-08-25 DOI: 10.1007/s00439-025-02770-w

Alexandra Filatova, Petr Vasiluev, Evgeniya Osipova, Olga Ivanova, Natalia Semenova, Mikhail Skoblov

{"title":"uAUG-creating variant in the LDLR gene causes mild Familial hypercholesterolemia.","authors":"Alexandra Filatova, Petr Vasiluev, Evgeniya Osipova, Olga Ivanova, Natalia Semenova, Mikhail Skoblov","doi":"10.1007/s00439-025-02770-w","DOIUrl":"10.1007/s00439-025-02770-w","url":null,"abstract":"Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein (LDL) levels, leading to early-onset cardiovascular disease. FH is primarily caused by pathogenic variants in the LDLR gene, affecting cholesterol metabolism. We describe a family with a mild form of FH, in which gene panel sequencing identified a novel c.-8C>A variant in the LDLR 5'UTR. To assess its functional impact, we performed a luciferase assay and found that this variant partially reduces LDLR protein translation efficiency by introducing a novel upstream AUG (uAUG) start codon. This partial reduction in LDLR activity is consistent with the mild phenotype observed in the family. Additionally, we analyzed three previously reported LDLR 5'UTR variants (c.-5C>T, c.-14C>A, and c.-23A>C) but did not observe any significant effect on LDLR expression, suggesting that these variants are unlikely to contribute to disease development. These findings highlight the role of 5'UTR variants in LDLR expression and emphasize the importance of functional studies in variant classification for FH diagnostics.","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":" ","pages":"1001-1009"},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952139","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}

引用次数: 0

Correction: An augmented transformer model trained on protein family specific variant data leads to improved prediction of variants of uncertain significance. 更正：对蛋白质家族特异性变异数据进行训练的增强变压器模型可以改进对不确定意义变异的预测。

IF 3.6 2区生物学

Human Genetics Pub Date : 2025-10-01 DOI: 10.1007/s00439-025-02767-5

Dinesh Joshi, Swatantra Pradhan, Rakshanda Sajeed, Rajgopal Srinivasan, Sadhna Rana

引用次数: 0

Mutation-aware formulation: a genomic framework for equitable global dermocosmetics. 突变感知公式：公平的全球皮肤化妆品的基因组框架。

IF 3.6 2区生物学

Human Genetics Pub Date : 2025-10-01 Epub Date: 2025-08-13 DOI: 10.1007/s00439-025-02771-9

Eqram Rahman, William Richard Webb, Parinitha Rao, Jean D A Carruthers

{"title":"Mutation-aware formulation: a genomic framework for equitable global dermocosmetics.","authors":"Eqram Rahman, William Richard Webb, Parinitha Rao, Jean D A Carruthers","doi":"10.1007/s00439-025-02771-9","DOIUrl":"10.1007/s00439-025-02771-9","url":null,"abstract":"Despite advances in dermatogenomics, the global skincare industry continues to rely on generalized formulation strategies that overlook population-specific genetic variation. This study introduces a mutation-aware framework that bridges this translational gap through two novel metrics: the Mutation Burden Index (MBI)-which quantifies regional genetic vulnerability across nine core skin function domains-and the Population Compatibility Burden (PCB)-which measures the alignment between current commercial formulations and regional genomic needs. Using a curated database of more than 200 authenticated cosmeceutical products, we mapped ingredient functionality against regional MBI profiles. Results reveal a stark compatibility gap: regions with the highest burden (e.g., Africa, South Asia) receive the least functionally aligned products, with average compatibility scores as low as 0.35. In contrast, Europe-despite lower burden-achieves scores > 0.70. Simulated formulations informed by MBI scores increased compatibility to > 0.80 in underserved regions, demonstrating the potential for 50% gains in biological relevance without individualized genotyping. A machine learning classifier trained on MBI vectors achieved strong performance (F1 = 0.837), and SHAP-based interpretation highlighted barrier and pigmentation pathways as key drivers of product-region mismatch. In contrast to commercial AI platforms offer black-box personalization with minimal genomic input and no interpretability, our model provides transparent, biologically grounded, and reproducible formulation logic. By repositioning personalization from individual-level luxury to population-scale equity, this work establishes a practical foundation for genomically aligned skincare-anchored in functional biology, enabled by AI, and designed for global impact.","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":" ","pages":"1011-1034"},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834981","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}

引用次数: 0

Regulating genome language models: navigating policy challenges at the intersection of AI and genetics. 调控基因组语言模型：应对人工智能和遗传学交叉领域的政策挑战。

IF 3.6 2区生物学

Human Genetics Pub Date : 2025-10-01 Epub Date: 2025-09-16 DOI: 10.1007/s00439-025-02768-4

Bahrad A Sokhansanj, Gail L Rosen

{"title":"Regulating genome language models: navigating policy challenges at the intersection of AI and genetics.","authors":"Bahrad A Sokhansanj, Gail L Rosen","doi":"10.1007/s00439-025-02768-4","DOIUrl":"10.1007/s00439-025-02768-4","url":null,"abstract":"Genome Language Models (GLMs) represent a transformative convergence of artificial intelligence (AI) and genomics, offering unprecedented capabilities for biological discovery, healthcare innovation, and therapeutic design applications. However, these powerful tools create novel regulatory challenges that existing frameworks-whether AI governance or genomic privacy protections-cannot adequately address alone. This paper examines the critical regulatory gaps emerging at this intersection, highlighting tensions between AI principles that favor broad data access and genomic governance that demands stringent privacy protections and informed consent. We analyze how GLMs challenge conventional regulatory approaches as they pertain to applications in disease risk prediction, international research collaboration, and open-source model distribution. We propose a multilayered governance framework that combines policy innovations such as regulatory sandboxes and certification frameworks with technical solutions for privacy preservation and model interpretability. By developing adaptive governance strategies that bridge AI and genomic regulation, we can enable responsible GLM innovation while safeguarding individual rights, promoting equity, and addressing emerging biosecurity concerns in this rapidly evolving field.","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":" ","pages":"949-970"},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069422","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}

引用次数: 0

Biallelic loss-of-function variants of DNAH7 cause male infertility associated with asthenozoospermia in humans. DNAH7双等位基因功能缺失变异导致男性不育与人类弱精子症相关。

IF 3.6 2区生物学

Human Genetics Pub Date : 2025-10-01 Epub Date: 2025-08-14 DOI: 10.1007/s00439-025-02766-6

Guicheng Zhao, Jun Ma, Yingteng Zhang, Yan Wang, Chuan Jiang, Gan Shen, Dingming Li, Xiang Wang, Hengzhou Bai, Yi Zheng, Kun Tian, Juntao Yue, Xiaohui Jiang, Ying Shen

{"title":"Biallelic loss-of-function variants of DNAH7 cause male infertility associated with asthenozoospermia in humans.","authors":"Guicheng Zhao, Jun Ma, Yingteng Zhang, Yan Wang, Chuan Jiang, Gan Shen, Dingming Li, Xiang Wang, Hengzhou Bai, Yi Zheng, Kun Tian, Juntao Yue, Xiaohui Jiang, Ying Shen","doi":"10.1007/s00439-025-02766-6","DOIUrl":"10.1007/s00439-025-02766-6","url":null,"abstract":"Although variants in DNAH family genes have been suggested as a main contributor to asthenozoospermia in humans, the role of DNAH7 on male fertility remains largely unexplored. In this study, loss-of-function variants in DNAH7 were identified in two unrelated infertile men with asthenozoospermia through whole exome sequencing, including compound heterozygous variants c.9702_9705del (p.Phe3234Leufs*52) and c.768G > A (p.Trp256*) in Patient 1, and compound heterozygous variants c.5650 C > T (p.Arg1884*) and c.768G > A (p. Trp 256*) in Patient 2. Interestingly, transmission electron microscopy results indicated a severe loss of inner dynein arms (IDAs) in the sperm flagella of both patients. Furthermore, immunofluorescent staining revealed a marked reduction of DNAH7 and other IDA-associated proteins, such as DNAH3 and DNAH6, in the patients' spermatozoa. In contrast, the expression of the outer dynein arms (ODA)-associated proteins, including DNAH8, DNAH11, DNAH17 and DNAI1, was comparable to that in normal controls. Moreover, the infertility of the patients harboring DNAH7 mutations could be successfully overcome by intracytoplasmic sperm injection treatment. Taken together, our findings confirmed that DNAH7 variants may contribute to asthenozoospermia by affecting flagellar IDA assembly, thereby enhancing our understanding of phenotype-genotype correlations in male infertility.","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":" ","pages":"971-982"},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855068","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}

引用次数: 0