Morphosyntactic Abilities of SLI Probands

SLI先证者的形态句法能力

• 批准号: 8576446
• 负责人: MABEL L RICE
• 金额: $ 61.94万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 2015-02-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8576446
• 关键词: Address; Adolescence; Affect; Age; Archives; Award; Behavioral; Benchmarking; Brain; Candidate Disease Gene; Child; Childhood; Clinical; Comorbidity; Complex; Data; Data Collection; Databases; Detection; Development; Developmental Gene; Dimensions; Disease; Documentation; Education; Family; Family member; Genes; Genetic; Growth; Hereditary Disease; Impairment; Individual; Individual Differences; Intelligence; Intervention; Investigation; Language; Language Development; Language Tests; Linguistics; Link; Measures; Memory; Methods; Modeling; Molecular Genetics; Mothers; Nature; Outcome; Pattern; Performance; Phase; Phenotype; Reading; Sample Size; Sampling; Speech; Speech Sound; System; Time; Vocabulary; Work; developmental genetics; gene interaction; genetic analysis; genetic linkage analysis; genetic risk factor; improved; indexing; language onset; longitudinal database; proband; programs; public health relevance; specific language impairment

DESCRIPTION (provided by applicant): This program of investigation focuses on the genetics of Specific Language Impairment. We investigate longitudinal behavioral language phenotypes within a multi-gene developmental model involving a complex interaction of genetics, developmental brain changes, and overlapping phenotypes that intertwine throughout childhood with enduring individual differences in performance levels. Three previous award cycles have generated an empirical archive of proband and family data that is unique for the detailed documentation of longitudinal growth patterns across multiple indices of language, non-word repetition, reading, and speech sound acquisition. The archive previews a consistent picture for children with SLI of delayed onset of language, lower language levels that persist through adolescence, parallel growth trajectories to unaffected children although at lower levels of performance, and grammatical limitations out of sync with other dimensions of language although also following the growth trajectories of unaffected children. Family members show an elevated rate of affectedness. Co-morbidity of language and reading impairments is evident in affected children. Candidate gene linkage analyses suggest differential gene influences for language, speech, and reading impairments. In the proposed award cycle we will address some of the challenges inherent in these early genetic investigations of SLI. One is that current methods of phenotyping collapse across age levels, thereby obscuring potential developmental effects. The second is that the linguistic indicators are either relatively narrowly defined or broadly defined by omnibus language tests, making it difficult to interpret the ways in which particular genetic effects would impact the emerging linguistic system. The third is that sample sizes yield low power for detection of potential gene interactions. In the proposed award cycle our specific aims are: (1) Compile a behavioral database of probands, controls, and family members to be used for developing growth phenotypes in language, reading, speech, and non-word repetition. (2) To investigate the relationships among grammatical markers, vocabulary, omnibus language test, verbal memory, reading and nonverbal intelligence measures in children with SLI and controls and how the relationships change over time. (3) Carry out molecular genetic analyses. The results will document growth trajectories of affected and unaffected children, to provide a longitudinal perspective on the outcomes of SLI; will clarify the nature of the language phenotype(s) and relationships with related abilities; and will identify potential genes of influence for the developmental trajectories across dimensions of language, reading and non-word repetition. The results would have implications for the development of clinical interventions that are benchmarked to onset of language, expected rates of change, and expected associations of language outcomes with reading, non-word repetition, nonverbal intelligence, and mother's education.

描述（由申请人提供）：该调查计划的重点是特定语言障碍的遗传学。我们研究了多基因发育模型中的纵向行为语言表型，这些模型涉及遗传学的复杂相互作用，发育性大脑变化以及重叠的表型，这些表型与整个童年时期与绩效水平的持续个体差异交织在一起。以前的三个奖励周期产生了一个对概率和家庭数据的经验档案，对于跨语言，非单词重复，阅读和语音声音获取的纵向增长模式的详细文档是独一无二的。该存档预览了语言发作延迟的儿童，较低的语言水平，持续到青春期的较低语言水平，对未受影响的儿童的平行生长轨迹以及与其他语言的其他维度不同步的语法限制，尽管也遵循未受影响的儿童的成长轨迹。家庭成员表现出较高的影响率。在受影响的儿童中，语言和阅读障碍的合并症很明显。候选基因链接分析表明，语言，语音和阅读障碍的差异基因影响。在拟议的奖励周期中，我们将解决SLI早期遗传研究所固有的一些挑战。一种是当前的表型跨年龄级别崩溃的方法，从而掩盖了潜在的发育效果。第二个是语言指标是由综合语言测试对相对狭义的定义或广泛定义的，因此很难解释特定遗传效应会影响新兴语言系统的方式。第三个是样本量产生低功率以检测潜在基因相互作用。在拟议的奖励周期中，我们的具体目的是：（1）汇编一个概率，控制和家庭成员的行为数据库，用于在语言，阅读，言语和非词重复中开发增长表型。 （2）研究语法标记，词汇，综合语言测试，口头记忆，阅读和非语言智力测量的关系，以及与控制和控制的儿童的非言语智力测量以及关系如何随时间变化。 （3）进行分子遗传分析。结果将记录受影响和未受影响的儿童的生长轨迹，以对SLI的结果提供纵向观点；将阐明语言表型的性质以及与相关能力的关系；并将确定跨语言，阅读和非单词重复层面的发展轨迹的潜在影响基因。结果将对临床干预的发展产生影响，这些临床干预措施以语言发作，预期的变化率以及语言成果与阅读，非文字重复，非语言智能和母亲的教育的预期关联。