Exploratory subsetting of autism families based on savant skills improves evidence of genetic linkage to 15q11-q13
Exploratory subsetting of autism families based on savant skills improves evidence of genetic linkage to 15q11-q13
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DOI：
10.1097/01.chi.0000046868.56865.0f
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发表时间：
2003-07-01
影响因子：
13.3
通讯作者：
Sutcliffe, JS
中科院分区：
文献类型：
--
作者：
Nurmi, EL;Dowd, M;Sutcliffe, JS
目的：孤独症具有很高的遗传率，但其遗传病因复杂.在这些条件下鉴定易感基因座的一种方法是根据不同病例的遗传相关表型或生物学特征来定义更同质的家族子集。方法：作者使用自闭症诊断访谈中的项目进行了主成分分析，得出了六个变量集群，其中五个显示出显著的同胞相关性。在染色体15 q11-q13上孤独症候选区域的探索性遗传分析中测试这些表型子集的效用。结果如下：当孤独症样本的协作连锁研究划分的基础上，平均先证者得分的“学者技能”集群，在D15 S511的隐性模型下，在GABRB 3基因内的赔率的异质性对数，从0.6增加到2.6的家庭中，先证者有更大的学者技能的子集。结论：这些数据与15 q基因座对自闭症易感性的遗传贡献是一致的，在一个受影响的个体子集中表现出学者技能。在普拉德-威利综合征（Prader-Willi syndrome）患者中也发现了类似类型的技能，这是由于该染色体区域缺失所致。
Objective: Autism displays a remarkably high heritability but A complex genetic etiology. One approach to identifying susceptibility loci under these conditions is to define more homogeneous subsets of families on the basis of genetically relevant phenotypic or biological characteristics that vary from case to case. Method: The authors' performed a principal components analysis, using items from the Autism Diagnostic Interview, which resulted in six clusters of variables, five of which showed significant sib-sib correlation. the utility of these phenotypic subsets was tested in an exploratory genetic analysis of the autism candidate region on chromosome 15q11-q13. Results: When the Collaborative Linkage Study of Autism sample was divided, on the basis of mean proband score for the "savant skills" cluster, the heterogeneity logarithm of the odds under a recessive model at D15S511, within the GABRB3 gene, increased from 0.6 to 2.6 in the subset of families in which probands had greater savant skills. Conclusions: These data are consistent with the genetic contribution of a 15q locus to autism susceptibility in a subset of affected individuals exhibiting savant skills. Similar types of skills have been noted in individuals with Prader-Willi syndrome, which results from deletions of this chromosomal region.