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High-dimensional phenotyping to define the genetic basis of cellular morphology

Author

Listed:
  • Matthew Tegtmeyer

    (Broad Institute of MIT and Harvard
    Harvard University
    Centre for Gene Therapy and Regenerative Medicine, King’s College)

  • Jatin Arora

    (Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Samira Asgari

    (Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Beth A. Cimini

    (Imaging Platform, Broad Institute of MIT and Harvard)

  • Ajay Nadig

    (Broad Institute of MIT and Harvard
    Broad Institute of MIT and Harvard
    Massachusetts General Hospital)

  • Emily Peirent

    (Broad Institute of MIT and Harvard)

  • Dhara Liyanage

    (Broad Institute of MIT and Harvard)

  • Gregory P. Way

    (Imaging Platform, Broad Institute of MIT and Harvard)

  • Erin Weisbart

    (Imaging Platform, Broad Institute of MIT and Harvard)

  • Aparna Nathan

    (Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Tiffany Amariuta

    (Harvard Medical School
    Harvard T.H. Chan School of Public Health
    University of California
    University of California)

  • Kevin Eggan

    (Broad Institute of MIT and Harvard
    Harvard University)

  • Marzieh Haghighi

    (Imaging Platform, Broad Institute of MIT and Harvard)

  • Steven A. McCarroll

    (Broad Institute of MIT and Harvard
    Harvard Medical School
    Harvard Medical School)

  • Luke O’Connor

    (Broad Institute of MIT and Harvard
    Harvard Medical School)

  • Anne E. Carpenter

    (Imaging Platform, Broad Institute of MIT and Harvard)

  • Shantanu Singh

    (Imaging Platform, Broad Institute of MIT and Harvard)

  • Ralda Nehme

    (Broad Institute of MIT and Harvard
    Harvard University)

  • Soumya Raychaudhuri

    (Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Broad Institute of MIT and Harvard)

Abstract

The morphology of cells is dynamic and mediated by genetic and environmental factors. Characterizing how genetic variation impacts cell morphology can provide an important link between disease association and cellular function. Here, we combine genomic sequencing and high-content imaging approaches on iPSCs from 297 unique donors to investigate the relationship between genetic variants and cellular morphology to map what we term cell morphological quantitative trait loci (cmQTLs). We identify novel associations between rare protein altering variants in WASF2, TSPAN15, and PRLR with several morphological traits related to cell shape, nucleic granularity, and mitochondrial distribution. Knockdown of these genes by CRISPRi confirms their role in cell morphology. Analysis of common variants yields one significant association and nominate over 300 variants with suggestive evidence (P

Suggested Citation

  • Matthew Tegtmeyer & Jatin Arora & Samira Asgari & Beth A. Cimini & Ajay Nadig & Emily Peirent & Dhara Liyanage & Gregory P. Way & Erin Weisbart & Aparna Nathan & Tiffany Amariuta & Kevin Eggan & Marzi, 2024. "High-dimensional phenotyping to define the genetic basis of cellular morphology," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44045-w
    DOI: 10.1038/s41467-023-44045-w
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