Neuregulin 3 and its roles in schizophrenia risk and presentation.
Neuregulin 3 and its roles in schizophrenia risk and presentation.
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DOI：
10.1002/ajmg.b.32552
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Avramopoulos D
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文献类型：
--
作者：
Avramopoulos D
NeuRegins是一个由四个成员组成的表皮生长因子样信号分子家族，已经被研究了二十多年。他们在2002年首次被发现与精神分裂症有关，检测到NRG1基因的连锁和关联，几年后又检测到NRG3。然而，与疾病的联系并没有得到非常一致的观察。相比之下，NGR3变异与疾病表现的关联，特别是妄想症的存在，一直更一致。这似乎是通过基因选择性剪接的数量变化来调节的，这一点也一直被观察到。其他疾病和表型，无论是否患有精神疾病，也与NRG3有关。这些结果证明了行为遗传学研究的两个重要方面。第一个是，如果我们只考虑简单的风险，而不检查每个患者的个体表型的细节，我们将错过关于疾病生物学的重要见解。这是精准医学目标的一个重要方面。第二，变异的功能后果往往比特定基因转录水平的简单变化更为复杂，其中包括对选择性剪接的调节。为了准确地模拟和理解与表型相关的遗传变异的生物学后果，我们需要研究每个特定变异的生物学后果。简单地研究模型系统中直系基因零等位基因的后果，可能会错过感兴趣的基因组中亚型和/或功能变异的许多细微差别。
Neuregulins, a four-member family of epidermal growth factor-like signaling molecules, have been studied for over two decades. They were first implicated in schizophrenia in 2002 with the detection of linkage and association at the NRG1 locus followed after a few years by NRG3. However the associations with disease have not been very consistently observed. In contrast, association of NGR3 variants with disease presentation, specifically the presence of delusions, has been more consistent. This appears to be mediated by quantitative changes in the alternative splicing of the gene, which has also been consistently observed. Additional diseases and phenotypes, psychiatric or not, have also been connected with NRG3. These results demonstrate two important aspects of behavioral genetics research. The first is that if we only consider simple risk and fail to examine the details of each patient’s individual phenotype, we will miss important insights on the disease biology. This is an important aspect of the goals of precision medicine. The second is that the functional consequences of variants are often more complex than simple alterations in levels of transcription of a particular gene, including, among others, regulation of alternative splicing. To accurately model and understand the biological consequences of phenotype - associated genetic variants, we need to study the biological consequences of each specific variant. Simply studying the consequences of a null allele of the orthologous gene in a model system, runs the risk of missing the many nuances of hypomorphic and/or gain of function variants in the genome of interest.
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影响因子：
11
作者：
Loukola, A.;Wedenoja, J.;Keskitalo-Vuokko, K.;Broms, U.;Korhonen, T.;Ripatti, S.;Sarin, A-P;Pitkaniemi, J.;He, L.;Happola, A.;Heikkila, K.;Chou, Y-L;Pergadia, M. L.;Heath, A. C.;Montgomery, G. W.;Martin, N. G.;Madden, P. A. F.;Kaprio, J.
通讯作者：
Kaprio, J.
影响因子：
7.8
作者：
Bao, JX;Wolpowitz, D;Role, LW;Talmage, DA
通讯作者：
Talmage, DA
DOI：
10.4137/ebo.s10211
发表时间：
2013
期刊：
Evolutionary bioinformatics online
影响因子：
--
作者：
Di Gaetano C;Matullo G;Piazza A;Ursino M;Gasparini M
通讯作者：
Gasparini M
影响因子：
2.4
作者：
Lee M;Kwon DY;Kim MS;Choi CR;Park MY;Kim AJ
通讯作者：
Kim AJ
影响因子：
9.8
作者：
Chen, Pei-Lung;Avramopoulos, Dimitrios;Valle, David
通讯作者：
Valle, David