Human GenomicsPub Date : 2026-04-11DOI: 10.1186/s40246-026-00957-4
Karolina Cernovska, Sabina Penazova, Kamila Stranska, Jakub Paweł Porc, Patricie Skalakova, Eva Ondrouskova, Tobias Rausch, Jan Svaton, Kristyna Tausova, Natalie Kazdova, Karol Pal, Jakub Hynst, Vladimir Benes, Marie Jarosova, Sarka Pospisilova, Jana Kotaskova, Karla Plevova
{"title":"Leveraging a spectrum of cytogenomics methods for profiling complex karyotypes in chronic lymphocytic leukemia.","authors":"Karolina Cernovska, Sabina Penazova, Kamila Stranska, Jakub Paweł Porc, Patricie Skalakova, Eva Ondrouskova, Tobias Rausch, Jan Svaton, Kristyna Tausova, Natalie Kazdova, Karol Pal, Jakub Hynst, Vladimir Benes, Marie Jarosova, Sarka Pospisilova, Jana Kotaskova, Karla Plevova","doi":"10.1186/s40246-026-00957-4","DOIUrl":"https://doi.org/10.1186/s40246-026-00957-4","url":null,"abstract":"","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147662452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human GenomicsPub Date : 2026-04-11DOI: 10.1186/s40246-026-00962-7
Areej S Albawa'neh, Mais N Alqasrawi, Zeina N Al-Mahayri, Nour Al Dain Marzouka, Lilas Dabaghie, Dana Hamza, Lubna Q Khasawneh, Virendra Misra, Husam Ouda, Bassam R Ali
{"title":"HMGCR genetic variation and risk of new-onset type 2 diabetes in statin users.","authors":"Areej S Albawa'neh, Mais N Alqasrawi, Zeina N Al-Mahayri, Nour Al Dain Marzouka, Lilas Dabaghie, Dana Hamza, Lubna Q Khasawneh, Virendra Misra, Husam Ouda, Bassam R Ali","doi":"10.1186/s40246-026-00962-7","DOIUrl":"https://doi.org/10.1186/s40246-026-00962-7","url":null,"abstract":"","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147662493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Integrated multiomics profiling of amniotic fluid exosomes reveals dysregulated lipid and protein signatures in fetal 22q11.2 deletion syndrome.","authors":"Hai Xiao, Tao Li, Mengting Zhang, Xue Lv, Yue Gao, Qiannan Guo, Zhenglong Guo, Hongdan Wang, Liangjie Guo, Hongyan Liu, Shixiu Liao, Dong Wu","doi":"10.1186/s40246-026-00963-6","DOIUrl":"https://doi.org/10.1186/s40246-026-00963-6","url":null,"abstract":"<p><strong>Background: </strong>Amniotic fluid exosomes (AF-Exos) are pivotal carriers of biological information during fetal development; however, their role in 22q11.2 Deletion Syndrome (22q11.2DS) remains unclear. To elucidate the molecular mechanisms underlying fetal anomalies in 22q11.2DS, this study performed a comprehensive multiomics analysis of AF-Exos obtained from 22q11.2DS fetuses (n = 5) and matched controls (n = 5).</p><p><strong>Results: </strong>While exosomal morphology and size distribution remained unaltered, integrated lipidomic and proteomic profiling revealed profound molecular remodeling. Lipidomics analysis revealed a specific suppression of diacylglycerols, triacylglycerols, and ceramides, accompanied by a shift in carbon chain length distribution. Concurrently, data-independent acquisition proteomics identified 329 differentially expressed proteins, highlighting a significant downregulation of PI4KA and widespread perturbations in pathways governing cardiovascular morphogenesis, angiogenesis, and SNARE-mediated vesicular transport. Integrated network analysis revealed strong correlations between the depletion of key lipids and reduced abundance of PI4KA and SNARE complex components, suggesting a potential interplay between lipid metabolism and vesicle trafficking.</p><p><strong>Conclusions: </strong>These findings, extending beyond the primary genetic driver TBX1, point to distinct alterations in lipid signaling and exosomal transport machinery in 22q11.2DS, suggesting a novel parallel pathogenic mechanism. This study provides a novel multiomics resource for understanding 22q11.2DS pathogenesis and generates valuable hypothesis-driven candidates for future mechanistic investigation.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147638719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human GenomicsPub Date : 2026-04-05DOI: 10.1186/s40246-026-00952-9
Jade Fauqueux, Roseline Caumes, Cindy Colson, Adeline Trauffler, Pierre Cleuziou, Caroline Thuillier, Pauline Planté-Bordeneuve, Marine Tessarech, Jamal Ghoumid, Thomas Smol
{"title":"Compound heterozygous structural variants resulting in CNTNAP2 biallelic loss-of-function: rare mechanisms unveiled by genome sequencing.","authors":"Jade Fauqueux, Roseline Caumes, Cindy Colson, Adeline Trauffler, Pierre Cleuziou, Caroline Thuillier, Pauline Planté-Bordeneuve, Marine Tessarech, Jamal Ghoumid, Thomas Smol","doi":"10.1186/s40246-026-00952-9","DOIUrl":"https://doi.org/10.1186/s40246-026-00952-9","url":null,"abstract":"<p><p>The CNTNAP2 gene encodes CASPR2, a transmembrane protein essential for neuronal development and synaptic function. Biallelic pathogenic variants cause Pitt-Hopkins-like syndrome, characterized by intellectual disability, epilepsy, and autistic features. We report two patients with a Pitt-Hopkins-like phenotype carrying compound heterozygous structural variants: an intragenic deletion in trans with a paracentric inversion. Short-read genome sequencing detected both variants, and long-read sequencing refined one breakpoint. Non-reccurent deletions involved exon 3, while CNTNAP2 breakpoints for both inversions were located in intron 1. These findings broaden the mutational spectrum of CNTNAP2 and underscore the value of genome sequencing in identifying complex structural variants.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147622835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human GenomicsPub Date : 2026-04-04DOI: 10.1186/s40246-026-00959-2
Yitian Zhou, Lukas M Lauschke, Volker M Lauschke
{"title":"Comprehensive overview of the global pharmacogenetic and functional variability in NUDT15.","authors":"Yitian Zhou, Lukas M Lauschke, Volker M Lauschke","doi":"10.1186/s40246-026-00959-2","DOIUrl":"10.1186/s40246-026-00959-2","url":null,"abstract":"<p><p>Thiopurine medications are widely used for the treatment of acute lymphoblastic leukemia and inflammatory bowel disease. However, thiopurine-induced hemotoxicity occurs in up to 30% of patients, which causes substantial morbidity and limits therapeutic success. These adverse effects are associated with genetic variation in TPMT and NUDT15, which encode key enzymes involved in thiopurine metabolism. While the global distribution of TPMT variability has been extensively studied, less is known about the ethnogeographic variability of NUDT15, and no meta-analysis of available population frequencies has been reported. In this study, we aggregated genetic data from 150 studies and repositories comprising genotypes from a total of 1,401,592 individuals across 55 countries. We further synthesize the available clinical evidence for functional effects of NUDT15*5 and NUDT15*6, which are currently considered as variants with indeterminate functional effects. This synthesis indicates that both alleles significantly increase thiopurine adverse event risk. We aggregate the genetic information to spectra of functional variability to generate the first global maps of NUDT15 metabolizer phenotypes. We observe a graded distribution of NUDT15 deficiency, peaking in East Asia (46% of all individuals exhibit reduced NUDT15 activity) and declining across Central Asia (13.6%), Middle Eastern populations (3.8%) and Europe (2.1%). NUDT15 deficiency is furthermore prevalent on the Western coast of South and Central America but absent in Africa. Overall, our results provide a valuable resource for population-specific NUDT15 allele and metabolizer phenotype distributions, which can guide thiopurine risk assessment on a global scale.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13069803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147618601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human GenomicsPub Date : 2026-03-27DOI: 10.1186/s40246-026-00951-w
Dan Qiu, Brenda Cabrera-Mendoza, Jun He, Lea Steele, Rachel Quaden, Kelly M Harrington, Sarah T Ahmed, J Michael Gaziano, Elizabeth J Gifford, Mihaela Aslan, Drew A Helmer, Elizabeth R Hauser, Renato Polimanti
{"title":"Genomic interplay between deployment exposures and Gulf War illness in Million Veteran Program participants.","authors":"Dan Qiu, Brenda Cabrera-Mendoza, Jun He, Lea Steele, Rachel Quaden, Kelly M Harrington, Sarah T Ahmed, J Michael Gaziano, Elizabeth J Gifford, Mihaela Aslan, Drew A Helmer, Elizabeth R Hauser, Renato Polimanti","doi":"10.1186/s40246-026-00951-w","DOIUrl":"10.1186/s40246-026-00951-w","url":null,"abstract":"","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147528531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human GenomicsPub Date : 2026-03-25DOI: 10.1186/s40246-026-00949-4
Angeliki I Katsafadou, Pål Ø Falnes, Elspeth Bruford, Bryony Braschi, Quinlin M Hanson, Matthew D Hall, David C Thompson, Daniel W Nebert, Vasilis Vasiliou
{"title":"Update of the Methyltransferase Gene Family: Classification, Evolution and Biological Functions.","authors":"Angeliki I Katsafadou, Pål Ø Falnes, Elspeth Bruford, Bryony Braschi, Quinlin M Hanson, Matthew D Hall, David C Thompson, Daniel W Nebert, Vasilis Vasiliou","doi":"10.1186/s40246-026-00949-4","DOIUrl":"10.1186/s40246-026-00949-4","url":null,"abstract":"","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13137591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147511938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human GenomicsPub Date : 2026-03-25DOI: 10.1186/s40246-025-00902-x
Birute Tumiene, David R Adams, Robert Allaway, Maria J Barrero, Chun-Hung Chan, Víctor Faundes, Vanessa S Fear, Polina Glezer, Claudia Fuchs, Tudor Groza, Elisa J F Houwink, Saumya Shekhar Jamuar, Mary Catherine V Letinturier, Richa Madan Lomash, Ratna Dua Puri, Juergen K V Reichardt, Ruty Mehrian-Shai, Francois H van der Westhuizen, Gaurav K Varshney, Shinya Yamamoto, Gareth Baynam
{"title":"Translating multi-omics into healthcare: requisites for scalable and equitable implementation.","authors":"Birute Tumiene, David R Adams, Robert Allaway, Maria J Barrero, Chun-Hung Chan, Víctor Faundes, Vanessa S Fear, Polina Glezer, Claudia Fuchs, Tudor Groza, Elisa J F Houwink, Saumya Shekhar Jamuar, Mary Catherine V Letinturier, Richa Madan Lomash, Ratna Dua Puri, Juergen K V Reichardt, Ruty Mehrian-Shai, Francois H van der Westhuizen, Gaurav K Varshney, Shinya Yamamoto, Gareth Baynam","doi":"10.1186/s40246-025-00902-x","DOIUrl":"10.1186/s40246-025-00902-x","url":null,"abstract":"","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13085408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147511927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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