Human Genetics最新文献

Bringing environment back into human evolution: why human genetics needs genome-environment association studies. 将环境带回人类进化：为什么人类遗传学需要基因组-环境关联研究。

IF 3.6 2区生物学

Human Genetics Pub Date : 2026-05-08 DOI: 10.1007/s00439-026-02838-1

Pei-Wei Sun

{"title":"Bringing environment back into human evolution: why human genetics needs genome-environment association studies.","authors":"Pei-Wei Sun","doi":"10.1007/s00439-026-02838-1","DOIUrl":"https://doi.org/10.1007/s00439-026-02838-1","url":null,"abstract":"Understanding the genetic basis of human adaptation to environmental pressures is a central question in evolutionary biology. Recent advancements in genome-environment association (GEA) methods have provided novel insights into how genetic variation is shaped by climate, diet, altitude, pathogens, and other environmental factors. However, despite significant progress in non-human studies, the application of GEA in human populations remains underused. This article synthesizes recent GEA methodological advancements, including redundancy analysis (RDA) and machine learning approaches, such as gradient forest (GF), to improve the detection of selection signals while accounting for demographic noise. Furthermore, I discuss the implications of historical GEA projection and genetic offset to human adaptation, particularly in the context of rapid urbanization and climate change. By integrating genomic, environmental, and epidemiological data, GEA has the potential not only to enhance our understanding of past human evolution but also to evaluate how allele-environment relationships may shift under future environmental change. By refining statistical models and expanding studies to diverse populations, GEA can play a critical role in elucidating the mechanisms underlying human adaptation and characterizing how selective forces shape the spatial distribution of adaptive alleles.","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":"145 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837428","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

A novel splice site variant in DEGS1 leads to aberrant splicing and loss of DEGS1 enzyme activity, a VUS resolved. DEGS1中一个新的剪接位点变异导致异常剪接和DEGS1酶活性的丧失，这是VUS解决的问题。

IF 3.6 2区生物学

Human Genetics Pub Date : 2026-05-06 DOI: 10.1007/s00439-026-02830-9

Holly C Beale, Victor Tse, Joanna Y Lee, Jon Akutagawa, Yusuph Mavura, Brandon Saint-John, Allison Cheney, Dennis R Mulligan, Guillermo Chacaltana, Martin Gutierrez, Jessica Tenney, Joseph T Shieh, Pierre-Marie Martin, Tiffany Yip, Ugur Hodoglugil, Alex J Fay, Angela N Brooks, Jessica Van Ziffle, Michael D Stone, Neil Risch, Jeremy R Sanford, Patrick Devine, Julie D Saba, Olena M Vaske, Anne Slavotinek

{"title":"A novel splice site variant in DEGS1 leads to aberrant splicing and loss of DEGS1 enzyme activity, a VUS resolved.","authors":"Holly C Beale, Victor Tse, Joanna Y Lee, Jon Akutagawa, Yusuph Mavura, Brandon Saint-John, Allison Cheney, Dennis R Mulligan, Guillermo Chacaltana, Martin Gutierrez, Jessica Tenney, Joseph T Shieh, Pierre-Marie Martin, Tiffany Yip, Ugur Hodoglugil, Alex J Fay, Angela N Brooks, Jessica Van Ziffle, Michael D Stone, Neil Risch, Jeremy R Sanford, Patrick Devine, Julie D Saba, Olena M Vaske, Anne Slavotinek","doi":"10.1007/s00439-026-02830-9","DOIUrl":"10.1007/s00439-026-02830-9","url":null,"abstract":"Pathogenic DEGS1 variants have been reported in individuals with autosomal recessive hypomyelinating leukodystrophy 18 (HLD18; MIM# 618404). Here we describe three participants with HLD features and a previously unreported homozygous DEGS1 5' splice site variant, c.825+4_825 + 5delAGinsTT (NM_003676.4). We used next-generation DNA and transcriptome sequencing, cell-based splicing assays, and tandem mass spectrometry to detect and characterize the variant's impact on DEGS1 expression. We then performed RNA structure probing and conventional antisense oligonucleotide screening to investigate molecular mechanisms for potential therapeutic intervention. We show that the splice site variant: (1) was sufficient to induce exon two skipping in most detected transcripts; (2) resulted in structural changes to the 5' and 3' splice site regions using RNA structure probing; and (3) corresponds to plasma sphingolipid profiles consistent with loss of sphingolipid delta(4)-desaturase activity. Our RNA and lipidomic evidence proved that the DEGS1 variant c.825+4_825 + 5delAGinsTT is pathogenic and suggested a mechanistic model that explains how exon two skipping is induced.","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":"145 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837374","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

Epigenetic silencing of DLEC1 correlates with tumor immune microenvironment and predicts immunotherapy prognosis in multiple cancers. DLEC1的表观遗传沉默与肿瘤免疫微环境相关并预测多种癌症的免疫治疗预后

IF 3.6 2区生物学

Human Genetics Pub Date : 2026-04-20 DOI: 10.1007/s00439-026-02828-3

Ruijie Ming, Qi Xiong, Shuh-Ying Tan, Lili Li, Shujie Bao, Jianhua Wang, Lijuan Zhao, Xiaoqian He, Zeze Zheng, Yan Wang, Xiaoyu Liu, Jun Tang, Zhongjun Wu, Tingxiu Xiang, Qian Tao

引用次数: 0

Improved functional JAG1 and NOTCH2 variant testing in patients with clinical or suspected Alagille syndrome using new low-Notch activity cells. 利用新型低notch活性细胞改进临床或疑似Alagille综合征患者JAG1和NOTCH2功能变异检测

IF 3.6 2区生物学

Human Genetics Pub Date : 2026-04-18 DOI: 10.1007/s00439-026-02832-7

Nicole Buhl, Eva-Doreen Pfister, Daniel V Oliveira, Fabio Turetti, Eberhard Lurz, Ulrich Baumann, Nataliya Di Donato, Thomas Illig, Britta Skawran, Emma R Andersson, Jan Mašek, Amelie Stalke

引用次数: 0

Correction: Variants in NR6A1 as a cause for congenital renal, vertebral and uterine anomalies. 更正：NR6A1变异是先天性肾脏、椎体和子宫异常的原因。

IF 3.6 2区生物学

Human Genetics Pub Date : 2026-04-13 DOI: 10.1007/s00439-026-02829-2

Adeline Jacquinet, Lydie Flasse, Manon Dohet, Romane Vanhaeren, Hélène Pendeville, Carol Saunders, Anna Lehman, Catherine Pienkowski, Karine Morcel, Daniel Guerrier, Vincent Bours, Bernard Peers

引用次数: 0

Integrating machine learning and spatial transcriptomics uncovers shared immunomodulatory deubiquitinases in MAFLD and HCC. 整合机器学习和空间转录组学揭示了MAFLD和HCC中共享的免疫调节去泛素酶。

IF 3.6 2区生物学

Human Genetics Pub Date : 2026-04-10 DOI: 10.1007/s00439-026-02833-6

Yu-Xi Han, Hongze Li, Wendi Xia, Junyi Ma, Jiaqi Zhang, Yiling Li

引用次数: 0

The genetic associations of DNAJC family members with Parkinson's disease: comprehensive evidence from burden analysis and Mendelian randomization. DNAJC家族成员与帕金森病的遗传关联：来自负担分析和孟德尔随机化的综合证据

IF 3.6 2区生物学

Human Genetics Pub Date : 2026-04-09 DOI: 10.1007/s00439-026-02831-8

Dehao Yang, Jingxuan Xu, Yusheng Zhu, Yangguang Lu, Ruotong Yao, Zihan Ye, Bohuai Yu, Jiaxuan Chen, Tingxuan Zhang, Bowen Liu, Suwen Huang, Guangyong Chen

{"title":"The genetic associations of DNAJC family members with Parkinson's disease: comprehensive evidence from burden analysis and Mendelian randomization.","authors":"Dehao Yang, Jingxuan Xu, Yusheng Zhu, Yangguang Lu, Ruotong Yao, Zihan Ye, Bohuai Yu, Jiaxuan Chen, Tingxuan Zhang, Bowen Liu, Suwen Huang, Guangyong Chen","doi":"10.1007/s00439-026-02831-8","DOIUrl":"https://doi.org/10.1007/s00439-026-02831-8","url":null,"abstract":"Background: Recent studies suggested that genetic mutations in the DNAJC family might elevate the risk of Parkinson's disease (PD). Nevertheless, the role of some DNAJC genes in PD remains controversial, and previous studies lacked downstream research. In this study, we aim to explore the relationship between DNAJC family genes and PD in a European cohort through a comprehensive method.Methods: Rare variants were identified by whole-exome sequencing from a cohort of 403 PD patients and 182 healthy controls. Fisher's exact test was conducted to assess the allelic associations. Gene-based burden analysis was conducted to detect the enrichment effect of mutations in DNAJC genes. Mendelian randomization was performed to explore the association of gene expression levels with PD risk. Finally, colocalization analysis was used to explore the shared genetic structure of DNAJC and PD.Results: In total, we identified 464 rare variants, 437 of which were significant at the allele level. At the gene level, rare variants in 7 genes (DNAJC1, DNAJC6, DNAJC10, DNAJC11, DNAJC13, DNAJC16 and DNAJC27) were enriched in PD patients. At the gene expression level, a positive causal association of DNAJC13 with PD was revealed. Colocalization analysis reinforced the genetic associations of DNAJC13 and DNAJC19 with PD risk by identifying shared variants.Conclusions: We provided convergent genetic evidence supporting DNAJC13 as a susceptibility gene for PD. We presented the first evidence that rare variants in DNAJC1, DNAJC11 and DNAJC16 were enriched in PD patients, and replicated the previously reported associations of DNAJC6, DNAJC10 and DNAJC27 with PD.","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":"145 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147638703","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

DNA methylation signatures from peripheral blood revealed epigenetic alterations in Fanconi anemia. 外周血DNA甲基化特征揭示了范可尼贫血的表观遗传改变。

IF 3.6 2区生物学

Human Genetics Pub Date : 2026-03-27 DOI: 10.1007/s00439-026-02827-4

Merin George, Sumit Halder, Shafi Gowhar, Anjali Shah, Somprakash Dhangar, Jagadeeshwar Ghatanatti, Ramesh Aarthi, Pranoti Kini, Mamta Mangalani, Aruna Rajendran, Sandeep Nemani, Sangeeta Murlidar, Babu Rao Vundinti

引用次数: 0

The involvement of TNFRSF25 in age-related hearing loss. TNFRSF25在年龄相关性听力损失中的作用

IF 3.6 2区生物学

Human Genetics Pub Date : 2026-03-26 DOI: 10.1007/s00439-026-02826-5

Marie Valerie Roche, Pei-Ciao Tang, Denise Yan, Michelle Rose De Marchena, Maria Camila Robayo, Clemer Abad, Yan Guo, Feng Gong, Katherina Walz, Xue Zhong Liu

引用次数: 0

A comprehensive and accessible model for co-segregation analysis in BRCA1, BRCA2, and PALB2 variant classification. BRCA1、BRCA2和PALB2变体分类中共分离分析的一个全面和可访问的模型。

IF 3.6 2区生物学

Human Genetics Pub Date : 2026-03-26 DOI: 10.1007/s00439-025-02816-z

Setareh Moghadasi, Ramin Monajemi, Merel E Braspenning, Maaike P G Vreeswijk, Mar Rodríguez-Girondo

引用次数: 0