The aromatase gene CYP19A1: several genetic and functional lines of evidence supporting a role in reading, speech and language.
The aromatase gene CYP19A1: several genetic and functional lines of evidence supporting a role in reading, speech and language.
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DOI：
10.1007/s10519-012-9532-3
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发表时间：
2012-07
影响因子：
2.6
通讯作者：
Kere, Juha
中科院分区：
文献类型：
--
作者：
Anthoni, Heidi;Sucheston, Lara E.;Lewis, Barbara A.;Tapia-Paez, Isabel;Fan, Xiaotang;Zucchelli, Marco;Taipale, Mikko;Stein, Catherine M.;Hokkanen, Marie-Estelle;Castren, Eero;Pennington, Bruce F.;Smith, Shelley D.;Olson, Richard K.;Tomblin, J. Bruce;Schulte-Koerne, Gerd;Noethen, Markus;Schumacher, Johannes;Mueller-Myhsok, Bertram;Hoffmann, Per;Gilger, Jeffrey W.;Hynd, George W.;Nopola-Hemmi, Jaana;Leppanen, Paavo H. T.;Lyytinen, Heikki;Schoumans, Jacqueline;Nordenskjold, Magnus;Spencer, Jason;Stanic, Davor;Boon, Wah Chin;Simpson, Evan;Makela, Sari;Gustafsson, Jan-Ake;Peyrard-Janvid, Myriam;Iyengar, Sudha;Kere, Juha
关键词：
受CYP 19 A1基因15q21.2在言语和语言障碍连锁区的定位以及引起我们注意的一个阅读障碍个体中的罕见易位的启发，我们对CYP 19 A1作为阅读障碍和相关疾病的候选基因的性质进行了一系列研究。芳香化酶是细胞色素P450超家族的一员，它具有几个关键功能：催化雄激素转化为雌激素;在哺乳动物发育早期，它控制特定脑区的分化（例如，海马体中的局部雌激素合成调节突触可塑性和轴突生长）;它参与大脑的性别分化;在鸣禽和硬骨鱼中，它调节发声。我们的研究结果表明，CYP 19 A1的变化与阅读障碍作为一个分类特征，并与语言和言语的定量措施，如阅读，词汇，语音处理和口头运动技能。其大脑启动子区域附近的变化改变了转录因子结合，表明在CYP 19 A1表达中的调节作用。CYP 19 A1在人脑中的表达与阅读障碍易感基因如DYX 1C 1和ROBO 1的表达相关。芳香酶缺陷小鼠表现出皮质神经元密度增加和偶尔的皮质异位，也分别在Robo 1 −/−小鼠和人类睡眠障碍脑中观察到。芳香化酶抑制剂减少培养的大鼠神经元树突的生长。从这一广泛的证据，我们建议CYP 19 A1作为一个候选基因的人类认知功能牵连在阅读，讲话和语言。本文的在线版本（doi：10.1007/s10519-012-9532-3）包含补充材料，可供授权用户使用。
Inspired by the localization, on 15q21.2 of the CYP19A1 gene in the linkage region of speech and language disorders, and a rare translocation in a dyslexic individual that was brought to our attention, we conducted a series of studies on the properties of CYP19A1 as a candidate gene for dyslexia and related conditions. The aromatase enzyme is a member of the cytochrome P450 super family, and it serves several key functions: it catalyzes the conversion of androgens into estrogens; during early mammalian development it controls the differentiation of specific brain areas (e.g. local estrogen synthesis in the hippocampus regulates synaptic plasticity and axonal growth); it is involved in sexual differentiation of the brain; and in songbirds and teleost fishes, it regulates vocalization. Our results suggest that variations in CYP19A1 are associated with dyslexia as a categorical trait and with quantitative measures of language and speech, such as reading, vocabulary, phonological processing and oral motor skills. Variations near the vicinity of its brain promoter region altered transcription factor binding, suggesting a regulatory role in CYP19A1 expression. CYP19A1 expression in human brain correlated with the expression of dyslexia susceptibility genes such as DYX1C1 and ROBO1. Aromatase-deficient mice displayed increased cortical neuronal density and occasional cortical heterotopias, also observed in Robo1−/− mice and human dyslexic brains, respectively. An aromatase inhibitor reduced dendritic growth in cultured rat neurons. From this broad set of evidence, we propose CYP19A1 as a candidate gene for human cognitive functions implicated in reading, speech and language. The online version of this article (doi:10.1007/s10519-012-9532-3) contains supplementary material, which is available to authorized users.
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通讯作者：
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