ArticleCell2018
Functional Genetic Variants Revealed by Massively Parallel Precise Genome Editing.
Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers.
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Who cites it
144 citing papers in PubMed.
- Discovery and engineering of retrons for precise genome editing.Nature biotechnology · 2026Article
- The shape of fitness functions and the distribution of mutational effect sizes jointly limit adaptation by regulatory mutations.Nature ecology & evolution · 2026Article
- Prefoldin function links meiotic chromosome segregation with cellular remodeling and reveals tubulin sensitivity of the meiotic spindle.Science advances · 2026Article
- Construction of synthetic protein-binding non-genetic DNA systems in living cells.Nature chemistry · 2026Article
- Prefoldin function links meiotic chromosome segregation with cellular remodeling and reveals tubulin sensitivity of the meiotic spindle.bioRxiv : the preprint server for biology · 2026Article
- High-resolution genotype-free mapping of genetic variation with CRI-SPA-Map.Genome research · 2026Article
- Mapping functional non-coding variation in individual human genomes through haplotyping, multiomics, and deep learning.Nature communications · 2026Article
- Contrasting selective signatures of gene expression plasticity in response to antifungal clotrimazole and common environmental stresses in yeast.Nature communications · 2026Article
- Article
- Experimental evolution in an era of molecular manipulation.Nature reviews. Genetics · 2026Review
- Benchmarking the PAM compatibility of Cas12a variants for high-throughput yeast genetic variant engineering.Applied and environmental microbiology · 2025Article
- Structurally related phage helicases trigger type III-A3 retron-mediated anti-phage defense across diverse tailed phage families.Nucleic acids research · 2025Article
- Phage nuclease-mediated defense activation of the bacterial Retron-Eco7 toxin-antitoxin system.Nucleic acids research · 2025Article
- Endogenous fine-mapping and prioritization of functional regulatory elements in complex genetic loci.Cell genomics · 2025Article
- Functional synonymous mutations and their evolutionary consequences.Nature reviews. Genetics · 2025Review
- Predicting natural variation in the yeast phenotypic landscape with machine learning.Molecular systems biology · 2025Article
- The editable landscape of the yeast genome reveals hotspots of structural variant formation.Science advances · 2025Article
- A genome-to-proteome map reveals how natural variants drive proteome diversity and shape fitness.Science (New York, N.Y.) · 2025Article
- Improved vectors for retron-mediated CRISPR-Cas9 genome editing in Saccharomyces cerevisiae.G3 (Bethesda, Md.) · 2025Article
- High-throughput evaluation of genetic variants with prime editing sensor libraries.Nature biotechnology · 2025Article
84 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors.
Funding
Abstract
A major challenge in genetics is to identify genetic variants driving natural phenotypic variation. However, current methods of genetic mapping have limited resolution. To address this challenge, we developed a CRISPR-Cas9-based high-throughput genome editing approach that can introduce thousands of specific genetic variants in a single experiment. This enabled us to study the fitness consequences of 16,006 natural genetic variants in yeast. We identified 572 variants with significant fitness differences in glucose media; these are highly enriched in promoters, particularly in transcription factor binding sites, while only 19.2% affect amino acid sequences. Strikingly, nearby variants nearly always favor the same parent's alleles, suggesting that lineage-specific selection is often driven by multiple clustered variants. In sum, our genome editing approach reveals the genetic architecture of fitness variation at single-base resolution and could be adapted to measure the effects of genome-wide genetic variation in any screen for cell survival or cell-sortable markers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.