Cook E H, Courchesne R Y, Cox N J, Lord C, Gonen D, Guter S J, Lincoln A, Nix K, Haas R, Leventhal B L, Courchesne E
Department of Psychiatry, University of Chicago, Chicago, IL 60637, USA.
Am J Hum Genet. 1998 May;62(5):1077-83. doi: 10.1086/301832.
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 acidA 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.
自闭症谱系障碍是一种复杂的遗传性疾病。由于之前有报道称自闭症谱系障碍患者存在普拉德-威利/安吉尔曼综合征关键区域的重复，我们在15q11 - 13区域筛选了多个标记，以检测连锁不平衡。研究了140个家庭，主要由一名患有自闭症谱系障碍的儿童及其父母组成。通过多重PCR和毛细管电泳进行基因分型。鉴定出两名患有15号染色体间质性重复的儿童，并将其排除在进一步的连锁不平衡分析之外。对15q11 - 13上的9个位点使用多等位基因传递不平衡检验（MTDT），结果显示自闭症谱系障碍与γ-氨基丁酸A受体亚基基因GABRB3 155CA - 2中的一个标记之间存在连锁不平衡（MTDT 28.63，10自由度，P = 0.0014）。未发现等位基因传递存在亲本来源效应的证据。GABRB3作为一个位置和功能候选基因，与连锁不平衡数据相结合，表明需要进一步研究GABRB3或其相邻基因在自闭症谱系障碍中的作用。
