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Detection and analysis of complex structural variation in human genomes across populations and in brains of donors with psychiatric disorders.
Zhou, Bo; Arthur, Joseph G; Guo, Hanmin; Kim, Taeyoung; Huang, Yiling; Pattni, Reenal; Wang, Tao; Kundu, Soumya; Luo, Jay X J; Lee, HoJoon; Nachun, Daniel C; Purmann, Carolin; Monte, Emma M; Weimer, Annika K; Qu, Ping-Ping; Shi, Minyi; Jiang, Lixia; Yang, Xinqiong; Fullard, John F; Bendl, Jaroslav; Girdhar, Kiran; Kim, Minsu; Chen, Xi; Greenleaf, William J; Duncan, Laramie; Ji, Hanlee P; Zhu, Xiang; Song, Giltae; Montgomery, Stephen B; Palejev, Dean; Zu Dohna, Heinrich; Roussos, Panos; Kundaje, Anshul; Hallmayer, Joachim F; Snyder, Michael P; Wong, Wing H; Urban, Alexander E.
Afiliação
  • Zhou B; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA; Maternal and Child Health Research Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: boz
  • Arthur JG; Department of Statistics, Stanford University, Stanford, CA 94305, USA.
  • Guo H; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA; Maternal and Child Health Research Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Statistic
  • Kim T; School of Computer Science and Engineering, Pusan National University, Busan 46241, South Korea.
  • Huang Y; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Pattni R; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Wang T; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Kundu S; Department of Genetics, Stanford University, Stanford, CA 94305, USA; Department of Computer Science, Stanford University, Stanford, CA 94305, USA.
  • Luo JXJ; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Lee H; Division of Oncology, Department of Medicine, Stanford University, Stanford, CA 94305, USA.
  • Nachun DC; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Purmann C; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA; Maternal and Child Health Research Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Monte EM; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Weimer AK; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Qu PP; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Shi M; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Jiang L; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Yang X; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Fullard JF; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, U
  • Bendl J; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, U
  • Girdhar K; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, U
  • Kim M; School of Computer Science and Engineering, Pusan National University, Busan 46241, South Korea.
  • Chen X; Department of Statistics, Stanford University, Stanford, CA 94305, USA; Department of Biomedical Data Science, Stanford University, Stanford, CA 94305, USA.
  • Greenleaf WJ; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Duncan L; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA.
  • Ji HP; Division of Oncology, Department of Medicine, Stanford University, Stanford, CA 94305, USA.
  • Zhu X; Department of Statistics, Stanford University, Stanford, CA 94305, USA; Department of Statistics, Pennsylvania State University, University Park, PA 16802, USA; Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA 16802, USA.
  • Song G; School of Computer Science and Engineering, Pusan National University, Busan 46241, South Korea; Center for Artificial Intelligence Research, Pusan National University, Busan 46241, South Korea.
  • Montgomery SB; Department of Genetics, Stanford University, Stanford, CA 94305, USA; Maternal and Child Health Research Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Biomedical Data Science, Stanford University, Stanford, CA 94305, USA; Department of Pathology, Stanford
  • Palejev D; Institute of Mathematics and Informatics, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria.
  • Zu Dohna H; Department of Biology, American University of Beirut, Beirut 11-0236, Lebanon.
  • Roussos P; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, U
  • Kundaje A; Department of Genetics, Stanford University, Stanford, CA 94305, USA; Department of Computer Science, Stanford University, Stanford, CA 94305, USA.
  • Hallmayer JF; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA.
  • Snyder MP; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Wong WH; Department of Statistics, Stanford University, Stanford, CA 94305, USA; Department of Biomedical Data Science, Stanford University, Stanford, CA 94305, USA. Electronic address: whwong@stanford.edu.
  • Urban AE; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA; Maternal and Child Health Research Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: aeu
Cell ; 2024 Sep 28.
Article em En | MEDLINE | ID: mdl-39353437
ABSTRACT
Complex structural variations (cxSVs) are often overlooked in genome analyses due to detection challenges. We developed ARC-SV, a probabilistic and machine-learning-based method that enables accurate detection and reconstruction of cxSVs from standard datasets. By applying ARC-SV across 4,262 genomes representing all continental populations, we identified cxSVs as a significant source of natural human genetic variation. Rare cxSVs have a propensity to occur in neural genes and loci that underwent rapid human-specific evolution, including those regulating corticogenesis. By performing single-nucleus multiomics in postmortem brains, we discovered cxSVs associated with differential gene expression and chromatin accessibility across various brain regions and cell types. Additionally, cxSVs detected in brains of psychiatric cases are enriched for linkage with psychiatric GWAS risk alleles detected in the same brains. Furthermore, our analysis revealed significantly decreased brain-region- and cell-type-specific expression of cxSV genes, specifically for psychiatric cases, implicating cxSVs in the molecular etiology of major neuropsychiatric disorders.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Cell Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Adicionar na Minha BVS
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PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Cell Ano de publicação: 2024 Tipo de documento: Article