Chen G K, Kono N, Geschwind D H, Cantor R M
Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-7088, USA.
Mol Psychiatry. 2006 Feb;11(2):214-20. doi: 10.1038/sj.mp.4001753.
Autism spectrum disorder (ASD) is a neurodevelopmental syndrome marked by impairments in social interactive functioning and communication skills, and the presence of repetitive and restrictive behaviors. Twin and linkage studies provide evidence that ASD is heritable and genetically complex. Genetic analyses of familial quantitative traits in those with ASD may help to reveal underlying risk genes. We report a quantitative trait locus (QTL) analysis of nonverbal communication (NVC) in 228 families from the autism genetics resource exchange (AGRE) ascertained for at least two siblings with ASD. QTL at 1p13-q12, 4q21-25, 7q35, 8q23-24, and 16p12-13 indicate that genes at these loci may contribute to the variation in NVC among those with ASD. Using the criteria of Lander and Kruglyak, the QTL at 1p13-q12 is 'suggestive', while the other four are 'possible'. To assess whether these QTL are likely to harbor genes contributing specifically to the deficits in NVC, linkage analysis of ASD sibships with the most severe NVC scores was conducted. The sibships were identified by ordered-subset analyses (OSA), and families with the most severe NVC scores displayed lod scores of 3.4 at 8q23-24 and 3.8 at 16p12-13, indicating that these two regions are likely to harbor gene(s) contributing to ASD by predisposing to deficits in NVC.
自闭症谱系障碍（ASD）是一种神经发育综合征，其特征为社交互动功能和沟通技能受损，以及存在重复和受限行为。双胞胎和连锁研究提供了证据，表明ASD具有遗传性且遗传结构复杂。对ASD患者家族性数量性状的遗传分析可能有助于揭示潜在的风险基因。我们报告了对来自自闭症遗传学资源交换库（AGRE）的228个家庭的非言语沟通（NVC）进行的数量性状基因座（QTL）分析，这些家庭中至少有两个患有ASD的兄弟姐妹。位于1p13 - q12、4q21 - 25、7q35、8q23 - 24和16p12 - 13的QTL表明，这些基因座上的基因可能导致ASD患者中NVC的变异。根据兰德和克鲁格利亚克的标准，1p13 - q12处的QTL为“提示性”，而其他四个为“可能性”。为了评估这些QTL是否可能包含专门导致NVC缺陷的基因，我们对NVC分数最严重的ASD同胞对进行了连锁分析。通过有序子集分析（OSA）确定了同胞对，NVC分数最严重的家庭在8q23 - 24处的对数优势分数为3.4，在16p12 - 13处为3.8，这表明这两个区域可能包含因易导致NVC缺陷而促成ASD的基因。
