Common inversion polymorphism at 17q21.31 affects expression of multiple genes in tissue-specific manner.
Common inversion polymorphism at 17q21.31 affects expression of multiple genes in tissue-specific manner.
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DOI：
10.1186/1471-2164-13-458
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发表时间：
2012-09-06
期刊：
影响因子：
4.4
通讯作者：
Ophoff RA
中科院分区：
文献类型：
--
作者：
de Jong S;Chepelev I;Janson E;Strengman E;van den Berg LH;Veldink JH;Ophoff RA
染色体17q21.31包含一个共同的倒位多态性约900 kb的人群与欧洲血统。两个不同的MAPT单倍型，H1和H2的描述与不同的连锁不平衡模式，反映在这个位点的倒位状态的区域。MAPT H1单倍型与进行性核上性麻痹、皮质基底节变性、帕金森病和阿尔茨海默病相关，而H2与17q21.31微缺失综合征相关的复发性缺失事件相关，17q21.31微缺失综合征是一种以发育迟缓和学习障碍为特征的疾病。在这项研究中，我们调查倒位对17q21.31区域基因表达的影响。我们发现，在反转的边缘和内部，有几个基因的表达受到影响;这些基因对全血或人脑的不同区域都有特异性。发现H1单倍型与LRRC 37 A4、PLEKH 1 M和MAPT的表达增加相关。相反，MGC 57346、LRRC 37 A和CRHR 1的表达降低与H1相关。迄今为止的研究集中在MAPT在倒位区的表达。然而，我们的研究结果表明，倒位状态也会影响17q21.31区域中其他基因的表达。鉴于倒位状态与不同神经系统疾病之间的联系，这些基因也可能以组织特异性方式参与疾病病理学。
Chromosome 17q21.31 contains a common inversion polymorphism of approximately 900 kb in populations with European ancestry. Two divergent MAPT haplotypes, H1 and H2 are described with distinct linkage disequilibrium patterns across the region reflecting the inversion status at this locus. The MAPT H1 haplotype has been associated with progressive supranuclear palsy, corticobasal degeneration, Parkinson’s disease and Alzheimer’s disease, while the H2 is linked to recurrent deletion events associated with the 17q21.31 microdeletion syndrome, a disease characterized by developmental delay and learning disability. In this study, we investigate the effect of the inversion on the expression of genes in the 17q21.31 region. We find the expression of several genes in and at the borders of the inversion to be affected; specific either to whole blood or different regions of the human brain. The H1 haplotype was found to be associated with an increased expression of LRRC37A4, PLEKH1M and MAPT. In contrast, a decreased expression of MGC57346, LRRC37A and CRHR1 was associated with H1. Studies thus far have focused on the expression of MAPT in the inversion region. However, our results show that the inversion status affects expression of other genes in the 17q21.31 region as well. Given the link between the inversion status and different neurological diseases, these genes may also be involved in disease pathology, possibly in a tissue-specific manner.
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影响因子：
1.7
作者：
Rao, P. N.;Li, W.;Ophoff, R. A.
通讯作者：
Ophoff, R. A.
影响因子：
3.5
作者：
Baker, M;Litvan, I;Hutton, M
通讯作者：
Hutton, M
影响因子：
11
作者：
通讯作者：
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影响因子：
--
作者：
Webb, Amy;Miller, Bruce;Wilhelmsen, Kirk C.
通讯作者：
Wilhelmsen, Kirk C.
影响因子：
4.4
作者：
Saris CG;Horvath S;van Vught PW;van Es MA;Blauw HM;Fuller TF;Langfelder P;DeYoung J;Wokke JH;Veldink JH;van den Berg LH;Ophoff RA
通讯作者：
Ophoff RA