Genetic analysis of GABRB3 as a candidate gene of autism spectrum disorders.
Genetic analysis of GABRB3 as a candidate gene of autism spectrum disorders.
复制标题
DOI：
10.1186/2040-2392-5-36
复制
发表时间：
2014
期刊：
影响因子：
6.2
通讯作者：
Gau SS
中科院分区：
文献类型：
--
作者：
Chen CH;Huang CC;Cheng MC;Chiu YN;Tsai WC;Wu YY;Liu SK;Gau SS
GABRB 3是染色体15 q12上的一个位置候选基因，与自闭症谱系障碍（ASD）的神经生物学有关。本研究的目的是检查GABRB 3与ASD的遗传关联。样本包括356例根据DSM-IV诊断标准临床诊断为ASD并经修订版自闭症诊断访谈确认的患者和386例无关对照。我们使用桑格测序法在所有参与者的基因组DNA中搜索GABRB 3的所有外显子区域和1.6 Kb的5′区域的突变。我们对该样本中检测到的变异进行了病例对照关联分析，并进行了报告基因测定，以评估5′调控区变异的功能影响。我们检测到六个已知的常见SNP;然而，它们与ASD无关。此外，在18例患者和6例对照中共检测到22种罕见变异（12种位于5′调控区，4种位于内含子，6种位于外显子）。患者组罕见变异的频率显著高于对照组（18/356 vs 6/386，比值比= 3.37，P = 0.007）。所有12种5′调控区的罕见变异仅在7例患者中检出，而在任何对照组中均未检出（7/356 vs. 0/386，Fisher精确检验，P = 0.006）。两名患者携带多种罕见变异。家庭研究表明，这些罕见的变异大多数是从父母那里传播的。报告基因分析显示，与两个野生型等位基因相比，4个位于5′调控区的罕见变异体和1个位于外显子1a非翻译区的罕见变异体具有较高的报告基因活性。我们的数据表明GABRB 3的罕见变异可能与ASD相关，并且GABRB 3表达增加可能有助于某些患者的ASD发病机制。临床试验注册标识符：NCT 00494754
GABRB3 is a position candidate gene at chromosome 15q12 that has been implicated in the neurobiology of autism spectrum disorders (ASD). The aim of this study was to examine the genetic association of GABRB3 with ASD. The sample consisted of 356 patients with clinical diagnosis of ASD according to the DSM-IV diagnostic criteria and confirmed by the Autism Diagnostic Interview-Revised and 386 unrelated controls. We searched for mutations at all the exonic regions and 1.6 Kb of the 5′ region of GABRB3 in the genomic DNA of all the participants using the Sanger sequencing. We implemented a case-control association analysis of variants detected in this sample, and conducted a reporter gene assay to assess the functional impact of variants at the 5′ regulatory region. We detected six known common SNPs; however, they were not associated with ASD. Besides, a total of 22 rare variants (12 at 5′ regulatory, 4 at intronic, and 6 at exonic regions) were detected in 18 patients and 6 controls. The frequency of rare variants was significantly higher in the patient group than in the control group (18/356 versus 6/386, odds ratio = 3.37, P = 0.007). All the 12 rare variants at the 5′ regulatory region were only detected in 7 patients, but not in any of the controls (7/356 versus 0/386, Fisher’s exact test, P = 0.006). Two patients carried multiple rare variants. Family studies showed that most of these rare variants were transmitted from their parents. Reporter gene assays revealed that four rare variants at the 5′ regulatory region and 1 at exon 1a untranslated region had elevated reporter gene activities compared to two wild type alleles. Our data suggest rare variants of GABRB3 might be associated with ASD, and increased GABRB3 expression may contribute to the pathogenesis of ASD in some patients. Clinical trial registration Identifier: NCT00494754
登录
查看更多内容
影响因子：
6.9
作者：
BAILEY, A;LECOUTEUR, A;RUTTER, M
通讯作者：
RUTTER, M
影响因子：
2.7
作者：
DeLorey, Timothy M.;Sahbaie, Peyman;Clark, J. David
通讯作者：
Clark, J. David
影响因子：
56.9
作者：
Gabriel, SB;Schaffner, SF;Altshuler, D
通讯作者：
Altshuler, D
影响因子：
7.3
作者：
Chien, Yi-Ling;Gau, Susan Shur-Fen;Gadow, Kenneth D.
通讯作者：
Gadow, Kenneth D.
DOI：
10.1002/ar.21299
发表时间：
2011-10
影响因子：
2
作者：
Fatemi, S. Hossein;Folsom, Timothy D.;Kneeland, Rachel E.;Liesch, Stephanie B.
通讯作者：
Liesch, Stephanie B.