Allele-specific expression (ASE) is a phenomenon in which one allele is preferentially expressed over the other. Genetic and epigenetic factors cause ASE by altering the final composition of a gene's product, leading to expression imbalances that can have functional consequences on phenotypes. Environmental signals also impact allele-specific expression, but how they contribute to this cross talk remains understudied. Here, we explored how genotype, parent-of-origin, tissue, sex, and dietary fat simultaneously influence ASE biases. Male and female mice from a F₁ reciprocal cross of the LG/J and SM/J strains were fed a high or low fat diet. We harnessed strain-specific variants to distinguish between two ASE classes: parent-of-origin-dependent (unequal expression based on parental origin) and sequence-dependent (unequal expression based on nucleotide identity). We present a comprehensive map of ASE patterns in 2853 genes across three tissues and nine environmental contexts. We found that both ASE classes are highly dependent on tissue and environmental context. They vary across metabolically relevant tissues, between males and females, and in response to dietary fat. We also found 45 genes with inconsistent ASE biases that switched direction across tissues and/or environments. Finally, we integrated ASE and QTL data from published intercrosses of the LG/J and SM/J strains. Our ASE genes are often enriched in QTLs for metabolic and musculoskeletal traits, highlighting how this orthogonal approach can prioritize candidate genes. Together, our results provide novel insights into how genetic, epigenetic, and environmental mechanisms govern allele-specific expression, which is an essential step toward deciphering the genotype-to-phenotype map.

中文翻译：

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遗传、表观遗传和环境机制控制等位基因特异性基因表达

等位基因特异性表达 (ASE) 是一种等位基因优先于另一个等位基因表达的现象。遗传和表观遗传因素通过改变基因产物的最终组成而导致 ASE，从而导致表达失衡，从而对表型产生功能性后果。环境信号也会影响等位基因特异性表达，但它们如何促成这种串扰仍有待研究。在这里，我们探讨了基因型、来源亲本、组织、性别和膳食脂肪如何同时影响 ASE 偏差。_{来自 F 1}的雄性和雌性小鼠LG/J 和 SM/J 菌株的相互交叉喂食高脂肪或低脂肪饮食。我们利用菌株特异性变体来区分两种 ASE 类别：依赖亲本（基于亲本来源的不等表达）和依赖序列（基于核苷酸同一性的不等表达）。我们在三种组织和九种环境背景下展示了 2853 个基因中 ASE 模式的综合图谱。我们发现这两种 ASE 类别都高度依赖于组织和环境背景。它们在代谢相关组织、男性和女性之间以及对膳食脂肪的反应各不相同。我们还发现了 45 个具有不一致 ASE 偏差的基因，这些基因在组织和/或环境中改变了方向。最后，我们整合了来自已发表的 LG/J 和 SM/J 菌株杂交的 ASE 和 QTL 数据。我们的 ASE 基因通常富含代谢和肌肉骨骼特征的 QTL，突出了这种正交方法如何优先考虑候选基因。总之，我们的研究结果为遗传、表观遗传和环境机制如何控制等位基因特异性表达提供了新的见解，这是破译基因型到表型图谱的重要一步。