Menold M M, Shao Y, Wolpert C M, Donnelly S L, Raiford K L, Martin E R, Ravan S A, Abramson R K, Wright H H, Delong G R, Cuccaro M L, Pericak-Vance M A, Gilbert J R
Department of Medicine and the Center for Human Genetics, Duke University Medical Center, Durham NC 27710, USA.
J Neurogenet. 2001;15(3-4):245-59. doi: 10.3109/01677060109167380.
Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain, acting via the GABAA receptors. The GABAA receptors are comprised of several different homologous subunits, forming a group of receptors that are both structurally and functionally diverse. Three of the GABAA receptor subunit genes (GABRB3, GABRA5 and GABRG3) form a cluster on chromosome 15q11-q13, in a region that has been genetically associated with autistic disorder (AutD). Based on these data, we examined 16 single nucleotide polymorphisms (SNPs) located within GABRB3, GABRA5 and GABRG3 for linkage disequilibrium (LD) in 226 AutD families (AutD patients and parents). Genotyping was performed using either OLA (oligonucleotide ligation assay), or SSCP (single strand conformation polymorphism) followed by DNA sequencing. We tested for LD using the Pedigree Disequilibrium Test (PDT). PDT results gave significant evidence that AutD is associated with two SNPs located within the GABRG3 gene (exon5_539T/C, p=0.02 and intron5_687T/C, p=0.03), suggesting that the GABRG3 gene or a gene nearby contributes to genetic risk in AutD.
γ-氨基丁酸（GABA）是大脑中主要的抑制性神经递质，通过GABAA受体发挥作用。GABAA受体由几种不同的同源亚基组成，形成了一组在结构和功能上都具有多样性的受体。GABAA受体亚基基因中的三个（GABRB3、GABRA5和GABRG3）在15号染色体q11-q13区域形成一个簇，该区域在遗传学上与自闭症谱系障碍（AutD）相关。基于这些数据，我们在226个自闭症谱系障碍家庭（自闭症谱系障碍患者及其父母）中检查了位于GABRB3、GABRA5和GABRG3内的16个单核苷酸多态性（SNP）的连锁不平衡（LD）情况。使用OLA（寡核苷酸连接测定法）或SSCP（单链构象多态性）随后进行DNA测序来进行基因分型。我们使用系谱不平衡检验（PDT）来测试连锁不平衡。PDT结果提供了重要证据，表明自闭症谱系障碍与位于GABRG3基因内的两个SNP相关（外显子5_539T/C，p = 0.02和内含子5_687T/C，p = 0.03），这表明GABRG3基因或其附近的一个基因对自闭症谱系障碍的遗传风险有影响。
