Dominance is common in mammals and is associated with trans-acting gene expression and alternative splicing.
Dominance is common in mammals and is associated with trans-acting gene expression and alternative splicing.
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DOI：
10.1186/s13059-023-03060-2
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发表时间：
2023-09-29
期刊：
影响因子：
12.3
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中科院分区：
文献类型：
--
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显性和其他非加性遗传效应产生于等位基因之间的相互作用，从历史上看，这些现象在数量遗传学中发挥着重要作用。然而，大多数全基因组关联研究(GWAS)假设等位基因是相加作用的。我们系统地研究了三个哺乳动物群体中的574个生理和基因表达性状的显性和加性：F2杂交猪、大鼠异质群体和小鼠异质群体。在所有物种的所有生理性状中，显性约占可遗传变异的四分之一。血液学和免疫学性状表现出最高的显性变异，可能反映了对病原体的平衡选择。虽然大多数数量性状座位(QTL)都可以作为加性QTL检测到，但我们在猪、大鼠和小鼠身上分别发现了154个、和62个新的显性QTL，这些QTL作为加性QTL不能检测到。同样，尽管大多数顺式作用QTL是加性的，但基因表达表现出很大一部分显性方差，而反式作用eQTL则表现为显性丰富。导致显性生理QTL的基因不太可能在物理上与其QTL相连，而是通过反式显性eQTL起作用。此外，在异种系大鼠中，数千个eQTL与具有复杂加性和显性结构的选择性剪接异构体相关，这表明了一种可能的显性机制。虽然遗传性主要是加性的，但许多哺乳动物的遗传效应是显性的，可能通过不同的机制产生。因此，在GWA中同时考虑加性和显性效应是有利的，以提高威力并揭示因果关系。网上版载有补充材料，可在10.1186/s13059-023-03060-2查阅。
Dominance and other non-additive genetic effects arise from the interaction between alleles, and historically these phenomena play a major role in quantitative genetics. However, most genome-wide association studies (GWAS) assume alleles act additively. We systematically investigate both dominance—here representing any non-additive within-locus interaction—and additivity across 574 physiological and gene expression traits in three mammalian stocks: F2 intercross pigs, rat heterogeneous stock, and mice heterogeneous stock. Dominance accounts for about one quarter of heritable variance across all physiological traits in all species. Hematological and immunological traits exhibit the highest dominance variance, possibly reflecting balancing selection in response to pathogens. Although most quantitative trait loci (QTLs) are detectable as additive QTLs, we identify 154, 64, and 62 novel dominance QTLs in pigs, rats, and mice respectively that are undetectable as additive QTLs. Similarly, even though most cis-acting expression QTLs are additive, gene expression exhibits a large fraction of dominance variance, and trans-acting eQTLs are enriched for dominance. Genes causal for dominance physiological QTLs are less likely to be physically linked to their QTLs but instead act via trans-acting dominance eQTLs. In addition, thousands of eQTLs are associated with alternatively spliced isoforms with complex additive and dominant architectures in heterogeneous stock rats, suggesting a possible mechanism for dominance. Although heritability is predominantly additive, many mammalian genetic effects are dominant and likely arise through distinct mechanisms. It is therefore advantageous to consider both additive and dominance effects in GWAS to improve power and uncover causality. The online version contains supplementary material available at 10.1186/s13059-023-03060-2.
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影响因子：
3.7
作者：
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