Screening of nine candidate genes for autism on chromosome 2q reveals rare nonsynonymous variants in the cAMP-GEFII gene
Screening of nine candidate genes for autism on chromosome 2q reveals rare nonsynonymous variants in the cAMP-GEFII gene
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DOI：
10.1038/sj.mp.4001340
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发表时间：
2003-01-01
影响因子：
11
通讯作者：
Maestrini, E
中科院分区：
文献类型：
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作者：
Bacchelli, E;Blasi, F;Maestrini, E
几次基因组扫描的结果表明，染色体2q21-q33可能包含自闭症易感位点。我们研究了9个位置和功能候选基因的潜在贡献：TBR-1；GAD1;DLX1;DLX2;cAMP-GEFII;CHN1;ATF2;HOXD1和NEUROD1。筛选这些基因的DNA变异和使用基因内单核苷酸多态性进行关联分析并没有提供证据表明它们在自闭症的病因学中起主要作用。然而，在cAMP-GEFII基因中发现了四个罕见的非同义变体。这些变异存在于五个家庭中，它们与自闭症表型分离，并且在对照个体中未观察到。这些变异的意义尚不清楚，因为它们在IMGSAC家族中的低频率并不能解释2q位点上相对较强的连锁信号。需要进一步的研究来阐明cAMP-GEFII基因变异对自闭症易感性的贡献。
The results from several genome scans indicate that chromosome 2q21-q33 is likely to contain an autism susceptibility locus. We studied the potential contribution of nine positional and functional candidate genes: TBR-1; GAD1; DLX1; DLX2; cAMP-GEFII; CHN1; ATF2; HOXD1 and NEUROD1. Screening these genes for DNA variants and association analysis using intragenic single nucleotide polymorphisms did not provide evidence for a major role in the aetiology of autism. Four rare nonsynonymous variants were identified, however, in the cAMP-GEFII gene. These variants were present in five families, where they segregate with the autistic phenotype, and were not observed in control individuals. The significance of these variants is unclear, as their low frequency in IMGSAC families does not account for the relatively strong linkage signal at the 2q locus. Further studies are needed to clarify the contribution of cAMP-GEFII gene variants to autism susceptibility.