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- W3037887675 abstract "Summary Tens of thousands of genetic variants shape human phenotypes, mostly by unknown cellular mechanisms. Here we describe Census-seq, a way to measure cellular phenotypes in cells from many people simultaneously. Analogous to pooled CRISPR screens but for natural variation, Census-seq associates cellular phenotypes to donors’ genotypes by quantifying the presence of each donor’s DNA in cell “villages” before and after sorting or selection for cellular traits of interest. Census-seq enables population-scale cell-biological phenotyping with low cost and high internal control. We demonstrate Census-seq through investigation of genetic effects on the SMN protein whose deficiency underlies spinal muscular atrophy (SMA). Census-seq quantified and mapped effects of many common alleles on SMN protein levels and response to SMN-targeted therapeutics, including a common, cryptic non-responder allele. We provide tools enabling population-scale cell experiments and explain how Census-seq can be used to map genetic effects on diverse cell phenotypes. Abstract Figure Highlights Census-seq reveals how inherited genetic variation affects cell phenotypes Genetic analysis of cellular traits in cell villages of >100 donors Characterizing human alleles that shape SMN protein expression and drug responses Development of protocols and software to enable cellular population genetics" @default.
- W3037887675 created "2020-07-02" @default.
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- W3037887675 date "2020-06-29" @default.
- W3037887675 modified "2023-10-16" @default.
- W3037887675 title "Mapping genetic effects on cellular phenotypes with “cell villages”" @default.
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- W3037887675 doi "https://doi.org/10.1101/2020.06.29.174383" @default.
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