title: Constraint and divergence of global gene expression in the mammalian embryo.
abstract: The effects of genetic variation on gene regulation in the developing mammalian embryo remain largely unexplored. To globally quantify these effects, we crossed two divergent mouse strains and asked how genotype of the mother or of the embryo drives gene expression phenotype genomewide. Embryonic expression of 331 genes depends on the genotype of the mother. Embryonic genotype controls allele-specific expression of 1594 genes and a highly overlapping set of cis-expression quantitative trait loci (eQTL). A marked paucity of trans-eQTL suggests that the widespread expression differences do not propagate through the embryonic gene regulatory network. The cis-eQTL genes exhibit lower-than-average evolutionary conservation and are depleted for developmental regulators, consistent with purifying selection acting on expression phenotype of pattern formation genes. The widespread effect of maternal and embryonic genotype in conjunction with the purifying selection we uncovered suggests that embryogenesis is an important and understudied reservoir of phenotypic variation.
authors: Department of Pathology, Stanford University School of Medicine, Stanford, United States.
authors: Noah
authors: N
authors: Spies
authors: Department of Pathology, Stanford University School of Medicine, Stanford, United States.
authors: Cheryl L
authors: CL
authors: Smith
authors: Department of Computer Science, Stanford University, Stanford, United States.
authors: Jesse M
authors: JM
authors: Rodriguez
authors: Department of Genetics, Stanford University School of Medicine, Stanford, United States.
authors: Julie C
authors: JC
authors: Baker
authors: Department of Computer Science, Stanford University, Stanford, United States.
authors: Serafim
authors: S
authors: Batzoglou
authors: Department of Pathology, Stanford University School of Medicine, Stanford, United States.
authors: Arend
authors: A
authors: Sidow
mesh_terms: D000483:Alleles; D000818:Animals; D005075:Biological Evolution; D003433:Crosses, Genetic; D004622:Embryo, Mammalian; D047108:Embryonic Development / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D014644:Genetic Variation; D005838:Genotype; D040582:Inheritance Patterns; D008297:Male; D051379:Mice; D010641:Phenotype; D040641:Quantitative Trait Loci
keywords: allele-specific expression; developmental biology; evolutionary biology; gene expression; genomics; mouse; parental effects; quantitative trait loci; stem cells