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Machine learning dissection of human accelerated regions in primate neurodevelopment.
Whalen, Sean; Inoue, Fumitaka; Ryu, Hane; Fair, Tyler; Markenscoff-Papadimitriou, Eirene; Keough, Kathleen; Kircher, Martin; Martin, Beth; Alvarado, Beatriz; Elor, Orry; Laboy Cintron, Dianne; Williams, Alex; Hassan Samee, Md Abul; Thomas, Sean; Krencik, Robert; Ullian, Erik M; Kriegstein, Arnold; Rubenstein, John L; Shendure, Jay; Pollen, Alex A; Ahituv, Nadav; Pollard, Katherine S.
Afiliação
  • Whalen S; Gladstone Institutes, San Francisco, CA 94158, USA.
  • Inoue F; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
  • Ryu H; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA; Pharmaceutical Sciences and Pharmacogenomics Graduate Program, University of Californ
  • Fair T; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Markenscoff-Papadimitriou E; Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA.
  • Keough K; Gladstone Institutes, San Francisco, CA 94158, USA; Pharmaceutical Sciences and Pharmacogenomics Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
  • Kircher M; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany; Institute of Human Genetics, University Medical Center Schleswig-Holstein, University of Lübeck, 23562 Lübeck, Germany.
  • Martin B; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
  • Alvarado B; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Elor O; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
  • Laboy Cintron D; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
  • Williams A; Gladstone Institutes, San Francisco, CA 94158, USA.
  • Hassan Samee MA; Gladstone Institutes, San Francisco, CA 94158, USA.
  • Thomas S; Gladstone Institutes, San Francisco, CA 94158, USA.
  • Krencik R; Department of Neurosurgery, Center for Neuroregeneration, Houston Methodist Research Institute, Houston, TX, USA.
  • Ullian EM; Departments of Ophthalmology and Physiology, University of California, San Francisco, San Francisco, CA, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA, USA.
  • Kriegstein A; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Rubenstein JL; Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA.
  • Shendure J; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, Seattle, WA 98195, USA; Brotman Baty Institute for Precision Medicine, Seattle, WA 98195, USA.
  • Pollen AA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurology, University of California, San Fr
  • Ahituv N; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA. Electronic address: nadav.ahituv@ucsf.edu.
  • Pollard KS; Gladstone Institutes, San Francisco, CA 94158, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA; Department of Epidemiology and Biostatistics and Institute for Computational Health Sciences, University of California, San Francisco, San Francisco, CA,
Neuron ; 111(6): 857-873.e8, 2023 03 15.
Article em En | MEDLINE | ID: mdl-36640767
ABSTRACT
Using machine learning (ML), we interrogated the function of all human-chimpanzee variants in 2,645 human accelerated regions (HARs), finding 43% of HARs have variants with large opposing effects on chromatin state and 14% on neurodevelopmental enhancer activity. This pattern, consistent with compensatory evolution, was confirmed using massively parallel reporter assays in chimpanzee and human neural progenitor cells. The species-specific enhancer activity of HARs was accurately predicted from the presence and absence of transcription factor footprints in each species. Despite these striking cis effects, activity of a given HAR sequence was nearly identical in human and chimpanzee cells. This suggests that HARs did not evolve to compensate for changes in the trans environment but instead altered their ability to bind factors present in both species. Thus, ML prioritized variants with functional effects on human neurodevelopment and revealed an unexpected reason why HARs may have evolved so rapidly.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Encéfalo / Pan troglodytes / Elementos Facilitadores Genéticos Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Encéfalo / Pan troglodytes / Elementos Facilitadores Genéticos Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article