A genomic screen of autism: Evidence for a multilocus etiology
A genomic screen of autism: Evidence for a multilocus etiology
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DOI：
10.1086/302497
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发表时间：
1999-08-01
影响因子：
9.8
通讯作者：
Myers, RM
中科院分区：
文献类型：
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作者：
Risch, N;Spiker, D;Myers, RM
我们通过连锁分析对最初的 90 个多重同胞进行了自闭症基因组筛选，其中包含父母，其中包含 97 个独立受影响的同胞对 (ASP)，并在 49 个额外的多重同胞中进行了随访，其中包含 50 个 ASP。总共对 519 个标记进行了基因分型，其中 362 个用于初始筛选，另外 157 个在后续筛选中进行了基因分型。作为对照，我们还在分析中纳入了未受影响的同胞，这为初始筛查提供了 51 个不一致的同胞对 (DSP)，为后续筛查提供了 29 个。在工作的初始阶段，我们观察到与 DSP（共享 50.8%）相比，ASP（共享 51.6%）中的血统身份（IBD）有所增加。 ASP 中的过度共享不能归因于少数基因座的影响，而是归因于 IBD 的整个分布的适度增加。这些结果与指定大量基因座（可能大于或等于 15 个）的模型最兼容，而与指定小于或等于 10 个基因座的模型不太兼容。初始扫描中获得的最大 LOD 分数是染色体 1p 上的标记；该区域在复制家族集中也显示出积极的共享，两个集合的最大多点 LOD 得分为 2.15。因此，该区域可能存在中等作用的基因。在其他研究中确定的候选区域中，我们仅获得了适度的积极或消极联系证据。我们的结果表明，通过连锁分析对易感位点进行定位克隆可能是一项艰巨的任务，可能需要其他方法。
We have conducted a genome screen of autism, by linkage analysis in an initial set of 90 multiplex sibships, with parents, containing 97 independent affected sib pairs (ASPs), with follow-up in 49 additional multiplex sibships, containing 50 ASPs. In total, 519 markers were genotyped, including 362 for the initial screen, and an additional 157 were genotyped in the follow-up. As a control, we also included in the analysis unaffected sibs, which provided 51 discordant sib pairs (DSPs) for the initial screen and 29 for the follow-up. In the initial phase of the work, we observed increased identity by descent (IBD) in the ASPs (sharing of 51.6%) compared with the DSPs (sharing of 50.8%). The excess sharing in the ASPs could not be attributed to the effect of a small number of loci but, rather, was due to the modest increase in the entire distribution of IBD. These results are most compatible with a model specifying a large number of loci (perhaps greater than or equal to 15) and are less compatible with models specifying less than or equal to 10 loci. The largest LOD score obtained in the initial scan was for a marker on chromosome 1p; this region also showed positive sharing in the replication family set, giving a maximum multipoint LOD score of 2.15 for both sets combined. Thus, there may exist a gene of moderate effect in this region. We had only modestly positive or negative linkage evidence in candidate regions identified in other studies. Our results suggest that positional cloning of susceptibility loci by linkage analysis may be a formidable task and that other approaches may be necessary.