Variants in doublecortin- and calmodulin kinase like 1, a gene up-regulated by BDNF, are associated with memory and general cognitive abilities.
Variants in doublecortin- and calmodulin kinase like 1, a gene up-regulated by BDNF, are associated with memory and general cognitive abilities.
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DOI：
10.1371/journal.pone.0007534
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发表时间：
2009-10-21
期刊：
影响因子：
3.7
通讯作者：
Steen VM
中科院分区：
文献类型：
--
作者：
Le Hellard S;Håvik B;Espeseth T;Breilid H;Løvlie R;Luciano M;Gow AJ;Harris SE;Starr JM;Wibrand K;Lundervold AJ;Porteous DJ;Bramham CR;Deary IJ;Reinvang I;Steen VM
人类的记忆和一般认知能力是复杂的功能，具有高遗传性和广泛的变异性。脑源性神经营养因子（BDNF）在哺乳动物记忆形成中发挥着重要作用。基于在海马中BDNF诱导的突触巩固过程中显著上调的基因的鉴定，我们选择了在来自挪威和苏格兰的三个独立样本中测试的遗传变异体，这些样本是检查认知能力的成年个体。在所有样本中，我们发现，在双皮质素和钙调蛋白激酶样1（DCLK1）基因的标记，显着相关的一般认知（智商分数）和言语记忆功能，抵制多重测试。DCLK1是一个具有多种转录本的复杂基因，其表达和功能各不相同。我们发现，短的变体都上调BDNF治疗后，在大鼠海马，他们在成年人的大脑中表达（主要是在皮质和海马）。我们证明，几个相关的变体位于潜在的替代启动子和顺式调控元件的基因，它们影响BDNF介导的短DCLK1转录本在报告系统中的表达。这些数据表明DCLK1是一个与人类记忆和认知功能相关的功能基因。
Human memory and general cognitive abilities are complex functions of high heritability and wide variability in the population. The brain-derived neurotrophic factor (BDNF) plays an important role in mammalian memory formation. Based on the identification of genes markedly up-regulated during BDNF-induced synaptic consolidation in the hippocampus, we selected genetic variants that were tested in three independent samples, from Norway and Scotland, of adult individuals examined for cognitive abilities. In all samples, we show that markers in the doublecortin- and calmodulin kinase like 1 (DCLK1) gene, are significantly associated with general cognition (IQ scores) and verbal memory function, resisting multiple testing. DCLK1 is a complex gene with multiple transcripts which vary in expression and function. We show that the short variants are all up-regulated after BDNF treatment in the rat hippocampus, and that they are expressed in the adult human brain (mostly in cortices and hippocampus). We demonstrate that several of the associated variants are located in potential alternative promoter- and cis-regulatory elements of the gene and that they affect BDNF-mediated expression of short DCLK1 transcripts in a reporter system. These data present DCLK1 as a functionally pertinent gene involved in human memory and cognitive functions.
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影响因子：
4.1
作者：
Deary IJ;Gow AJ;Taylor MD;Corley J;Brett C;Wilson V;Campbell H;Whalley LJ;Visscher PM;Porteous DJ;Starr JM
通讯作者：
Starr JM
影响因子：
4.8
作者：
Burgess, HA;Reiner, O
通讯作者：
Reiner, O
影响因子：
5.3
作者：
Hariri, AR;Goldberg, TE;Weinberger, DR
通讯作者：
Weinberger, DR
影响因子：
4.7
作者：
Holback, S;Adlerz, L;Iverfeldt, K
通讯作者：
Iverfeldt, K
DOI：
10.1002/ajmg.b.30150
发表时间：
2005-04-05
影响因子：
2.8
作者：
Dempster, E;Toulopoulou, T;Collier, DA
通讯作者：
Collier, DA