Combined linkage and linkage disequilibrium analysis of a motor speech phenotype within families ascertained for autism risk loci.
Combined linkage and linkage disequilibrium analysis of a motor speech phenotype within families ascertained for autism risk loci.
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DOI：
10.1007/s11689-010-9063-2
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发表时间：
2010-12
影响因子：
4.9
通讯作者：
Brzustowicz, Linda M.
中科院分区：
文献类型：
--
作者：
Flax, Judy F.;Hare, Abby;Azaro, Marco A.;Vieland, Veronica J.;Brzustowicz, Linda M.
关键词：
使用自闭症遗传资源交换（AGRE）数据集的行为和遗传信息，我们开发了表型，并研究了与运动言语障碍一致的表达性语言行为的自闭症谱系障碍（ASD）患者和非ASD患者的联系和关联。来自自闭症诊断访谈修订版（ADI-R）的言语和语言变量用于开发与非言语或难以理解的言语行为相关的运动言语表型（NVMSD：ALL）和仅限于无显著理解困难的个体的相关表型（NVMSD：C）。使用Affytek 5.0数据，PPL框架被用来评估支持或反对性状标记连锁和连锁不平衡（LD）的证据的强度。然后利用免疫途径分析（IPA）来鉴定潜在的基因以供进一步研究。我们根据两种与潜在运动性语言障碍一致的相关语言-言语表型确定了几个连锁峰：NVMSD：ALL的染色体1q24.2、3q25.31、4q22.3、5 p12、5q33.1、17 p12、17q11.2和17 q22，NVMSD：C的染色体4p15.2和21q22.2。虽然没有令人信服的证据关联下，这些峰，我们确定了几个潜在的基因使用IPA。结论：根据两种运动言语表型识别出多个连锁峰。在缺乏证据的关联下，这些峰，我们建议基因进一步调查的基础上，他们的生物功能。考虑到自闭症谱系障碍是复杂的，具有广泛的行为和大量的潜在基因，这些言语表型可能属于一组几个，当开发狭窄的，定义明确的表型时，应考虑试图减少遗传异质性。本文的在线版本（doi：10.1007/s11689-010-9063-2）包含补充材料，可供授权用户使用。
Using behavioral and genetic information from the Autism Genetics Resource Exchange (AGRE) data set we developed phenotypes and investigated linkage and association for individuals with and without Autism Spectrum Disorders (ASD) who exhibit expressive language behaviors consistent with a motor speech disorder. Speech and language variables from Autism Diagnostic Interview-Revised (ADI-R) were used to develop a motor speech phenotype associated with non-verbal or unintelligible verbal behaviors (NVMSD:ALL) and a related phenotype restricted to individuals without significant comprehension difficulties (NVMSD:C). Using Affymetrix 5.0 data, the PPL framework was employed to assess the strength of evidence for or against trait-marker linkage and linkage disequilibrium (LD) across the genome. Ingenuity Pathway Analysis (IPA) was then utilized to identify potential genes for further investigation. We identified several linkage peaks based on two related language-speech phenotypes consistent with a potential motor speech disorder: chromosomes 1q24.2, 3q25.31, 4q22.3, 5p12, 5q33.1, 17p12, 17q11.2, and 17q22 for NVMSD:ALL and 4p15.2 and 21q22.2 for NVMSD:C. While no compelling evidence of association was obtained under those peaks, we identified several potential genes of interest using IPA. Conclusion: Several linkage peaks were identified based on two motor speech phenotypes. In the absence of evidence of association under these peaks, we suggest genes for further investigation based on their biological functions. Given that autism spectrum disorders are complex with a wide range of behaviors and a large number of underlying genes, these speech phenotypes may belong to a group of several that should be considered when developing narrow, well-defined, phenotypes in the attempt to reduce genetic heterogeneity. The online version of this article (doi:10.1007/s11689-010-9063-2) contains supplementary material, which is available to authorized users.
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影响因子：
9.8
作者：
Feuk, Lars;Kalervo, Aino;Hannula-Jouppi, Katariina
通讯作者：
Hannula-Jouppi, Katariina
影响因子：
16.2
作者：
Garcia, Natalia V. De Marco;Jessell, Thomas M.
通讯作者：
Jessell, Thomas M.
影响因子：
9.8
作者：
Bartlett, CW;Goedken, R;Vieland, VJ
通讯作者：
Vieland, VJ
DOI：
10.1002/ajmg.1497
发表时间：
2001-08-08
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
Bradford, Y;Haines, J;Piven, J
通讯作者：
Piven, J
影响因子：
4.6
作者：
Hammond, R;Vivancos, V;Guthrie, S
通讯作者：
Guthrie, S