Sex-Specific Parent-of-Origin Allelic Expression in the Mouse Brain
Sex-Specific Parent-of-Origin Allelic Expression in the Mouse Brain
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DOI：
10.1126/science.1190831
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发表时间：
2010-08-06
期刊：
影响因子：
56.9
通讯作者：
Dulac, Catherine
中科院分区：
文献类型：
--
作者：
Gregg, Christopher;Zhang, Jiangwen;Dulac, Catherine
基因组印记导致父系遗传染色体相对于母系遗传染色体的基因优先表达。我们使用全基因组方法来揭示成年小鼠大脑中的性别特异性起源等位基因效应。我们的研究确定了优先选择的母系遗传的X染色体在雌性皮质的神经元。此外，对皮质和下丘脑的分析确定了347个具有性别特异性印记特征的常染色体基因。在下丘脑中，性别特异性印记基因主要存在于雌性，这表明父母对女儿下丘脑功能的影响。我们发现，白细胞介素-18，一个基因与疾病的性别特异性患病率，是受复杂的，区域性的，和性别特异性的父母在大脑中的影响。因此，父源效应为研究大脑功能和疾病中的性二态性提供了新的途径。
Genomic imprinting results in preferential gene expression from paternally versus maternally inherited chromosomes. We used a genome-wide approach to uncover sex-specific parent-of-origin allelic effects in the adult mouse brain. Our study identified preferential selection of the maternally inherited X chromosome in glutamatergic neurons of the female cortex. Moreover, analysis of the cortex and hypothalamus identified 347 autosomal genes with sex-specific imprinting features. In the hypothalamus, sex-specific imprinted genes were mostly found in females, which suggests parental influence over the hypothalamic function of daughters. We show that interleukin-18, a gene linked to diseases with sex-specific prevalence, is subject to complex, regional, and sex-specific parental effects in the brain. Parent-of-origin effects thus provide new avenues for investigation of sexual dimorphism in brain function and disease.