High-dimensional phenotyping to define the genetic basis of cellular morphology.
Nat Commun
; 15(1): 347, 2024 Jan 06.
Article
in En
| MEDLINE
| ID: mdl-38184653
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 < 10-6) of association with one or more morphology traits. We then use these data to make predictions about sample size requirements for increasing discovery in cellular genetic studies. We conclude that, similar to molecular phenotypes, morphological profiling can yield insight about the function of genes and variants.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Quantitative Trait Loci
/
Induced Pluripotent Stem Cells
Type of study:
Prognostic_studies
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2024
Document type:
Article
Affiliation country:
United States