RT Journal Article SR Electronic T1 Systems Genetics of Single Nucleotide Polymorphisms at the Drosophila Obp56h Locus JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.06.28.450219 DO 10.1101/2021.06.28.450219 A1 Sneha S. Mokashi A1 Vijay Shankar A1 Joel A. Johnstun A1 Wen Huang A1 Trudy F. C. Mackay A1 Robert R. H. Anholt YR 2021 UL http://biorxiv.org/content/early/2021/06/29/2021.06.28.450219.abstract AB Variation in quantitative traits arises from naturally segregating alleles with environmentally sensitive effects, but how individual variants in single genes affect the genotype-phenotype map and molecular phenotypes is not understood. We used CRISPR/Cas9 germline gene editing to generate naturally occurring variants with different site classes and allele frequencies in the Drosophila melanogaster Obp56h gene in a common genetic background. Single base pair changes caused large allele-specific and sexually dimorphic effects on the mean and micro-environmental variance for multiple fitness-related traits and in the Obp56h co-regulated transcriptome. However, these alleles were not associated with quantitative traits in the Drosophila Genetic Reference Panel, suggesting that the small allelic effects observed in genome wide association studies may be an artifact of averaging variable context-dependent allelic effects over multiple genetic backgrounds. Thus, the traditional infinitesimal additive model does not reflect the underlying biology of quantitative traits.Competing Interest StatementThe authors have declared no competing interest.