Linkage-disequilibrium mapping of autistic disorder, with 15q11-13 markers
Linkage-disequilibrium mapping of autistic disorder, with 15q11-13 markers
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DOI：
10.1086/301832
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发表时间：
1998-05-01
影响因子：
9.8
通讯作者：
Courchesne, E
中科院分区：
文献类型：
--
作者：
Cook, EH;Courchesne, RY;Courchesne, E
自闭症是一种复杂的遗传疾病。由于以前的报告与Prader-Willi/Angelman综合征的关键区域重复的自闭症患者，我们筛选了几个标记在15 q11 -13区域，连锁不平衡。研究了140个家庭，主要由一个自闭症儿童和父母组成。采用多重PCR和毛细管电泳技术进行基因分型，发现2例间质15号染色体重复，排除在进一步连锁不平衡分析之外。对15 q11 -13上的9个位点进行多等位基因传递不平衡检验（MTDT），发现自闭症与γ-氨基丁酸受体亚基基因GABRB 3 155 CA-2中的标记物之间存在连锁不平衡（MTDT 28.63，10 df，P = 0.0014）。没有证据表明父母的起源影响等位基因的传播。GABRB 3作为一个位置和功能的候选者与连锁不平衡数据一起沿着的收敛表明需要进一步研究GABRB 3或邻近基因在自闭症障碍中的作用。
Autistic disorder is a complex genetic disease. Because of previous reports of individuals with autistic disorder with duplications of the Prader-Willi/Angelman syndrome critical region, we screened several markers across the 15q11-13 region, for linkage disequilibrium. One hundred forty families, consisting predominantly of a child with autistic disorder and both parents, were studied. Genotyping was performed by use of multiplex PCR and capillary electrophoresis, Two children were identified who had interstitial chromosome 15 duplications and were excluded from further linkage-disequilibrium analysis. Use of the multiallelic transmission-disequilibrium test (MTDT), for nine loci on 15q11-13, revealed linkage disequilibrium between autistic disorder and a marker in the gamma-aminobutyric acid, receptor subunit gene, GABRB3 155CA-2 (MTDT 28.63, 10 df, P = .0014). No evidence was found for parent-of-origin effects on allelic transmission. The convergence of GABRB3 as a positional and functional candidate along with the linkage-disequilibrium data suggests the need for further investigation of the role of GABRB3 or adjacent genes in autistic disorder.