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Quantitative and functional interrogation of parent-of-origin allelic expression biases in the brain

机译:大脑中原产地等位基因表达偏倚的定量和功能研究

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摘要

The maternal and paternal genomes play different roles in mammalian brains as a result of genomic imprinting, an epigenetic regulation leading to differential expression of the parental alleles of some genes. Here we investigate genomic imprinting in the cerebellum using a newly developed Bayesian statistical model that provides unprecedented transcript-level resolution. We uncover 160 imprinted transcripts, including 41 novel and independently validated imprinted genes. Strikingly, many genes exhibit parentally biased—rather than monoallelic—expression, with different magnitudes according to age, organ, and brain region. Developmental changes in parental bias and overall gene expression are strongly correlated, suggesting combined roles in regulating gene dosage. Finally, brain-specific deletion of the paternal, but not maternal, allele of the paternally-biased Bcl-x, (Bcl2l1) results in loss of specific neuron types, supporting the functional significance of parental biases. These findings reveal the remarkable complexity of genomic imprinting, with important implications for understanding the normal and diseased brain.>DOI:
机译:由于基因组印迹,母本和父本基因组在哺乳动物的大脑中扮演着不同的角色,这是一种表观遗传学调控,导致某些基因的父母等位基因差异表达。在这里,我们使用新开发的贝叶斯统计模型来研究小脑中的基因组印迹,该模型提供了空前的笔录级别的分辨率。我们发现了160个印迹的转录本,包括41个新颖且经过独立验证的印迹基因。令人惊讶的是,许多基因表现出父母偏见的表达,而不是单等位基因,其表达随年龄,器官和大脑区域的不同而不同。父母偏见的发育变化与总体基因表达密切相关,表明在调节基因剂量方面的综合作用。最后,父系偏爱的Bcl-x(Bcl2l1)的父本(而不是母体)等位基因的大脑特异性缺失导致特定神经元类型的丧失,从而支持父母偏见的功能重要性。这些发现揭示了基因组印迹的显着复杂性,对于理解正常和患病的大脑具有重要意义。> DOI:

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