Incorporating language phenotypes strengthens evidence of linkage to autism
Incorporating language phenotypes strengthens evidence of linkage to autism
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DOI：
10.1002/ajmg.1497
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发表时间：
2001-08-08
期刊：
影响因子：
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通讯作者：
Piven, J
中科院分区：
文献类型：
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作者：
Bradford, Y;Haines, J;Piven, J
我们研究了将先证者和亲本结构语言表型信息纳入连锁分析的影响，我们在第一阶段受影响的兄弟姐妹对基因组筛选中发现了两个区域的最高信号：染色体13q和7q。由于自闭症的诊断标准之一是语言发育缺失或异常，我们对跟进7q染色体的发现特别感兴趣，因为之前有两份关于该区域与发育性语言障碍联系的报告。我们假设，如果语言表型与染色体7q位点的连锁遗传相关，那么合并父母表型将增加该位点的信号，并且大多数信号将来自两个先证者都有严重语言延迟的家庭子集。研究结果支持这些假设。我们在7q染色体上获得的连锁信号以及13q染色体上至少一个连锁信号主要归因于两个先证者都有语言延迟的家族亚群。只有当父母的语言障碍史也被纳入分析时，这一点才变得明显。虽然基于我们的数据，我们无法区分上位性模型或异质性模型，但我们初步得出结论，可能存在不止一个与语言发展相关的自闭症易感性位点。(C) 2001 Wiley-Liss, Inc。
We investigated the effect of incorporating information about proband and parental structural language phenotypes into linkage analyses in the two regions for which we found the highest signals in our first-stage affected sibling pair genome screen: chromosomes 13q and 7q. We were particularly interested in following up on our chromosome 7q finding in light of two prior reports of linkage of this region to developmental language disorder, since one of the diagnostic criteria for autism is absent or abnormal language development. We hypothesized that if the language phenotype were genetically relevant to linkage at the chromosome 7q locus, then incorporating parents phenotypes would increase the signal at that locus, and most of the signal would originate from the subset of families in which both probands had severe language delay. The results support these hypotheses. The linkage signals we obtained on chromosome 7q as well as at least one signal on chromosome 13q are mainly attributable to the subgroup of families in which both probands had language delay. This became apparent only when the parents' history of language-related difficulties was also incorporated into the analyses. Although based on our data, we were not able to distinguish between epistasis or heterogeneity models, we tentatively concluded that there may be more than one autism susceptibility locus related to language development. (C) 2001 Wiley-Liss, Inc.