Familial Study of Severe Phonology Disorders

严重音韵障碍的家族研究

• 批准号: 6914428
• 负责人: BARBARA A LEWIS
• 金额: $ 54.14万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6914428
• 关键词: age difference; behavior test; behavioral /social science research tag; behavioral genetics; clinical research; comorbidity; developmental genetics; family genetics; gene interaction; generation difference; genetic markers; genetic susceptibility; genotype; human subject; language development; language disorders; linkage mapping; longitudinal human study; phenotype; phonology; polymerase chain reaction; preschool child (1-5); quantitative trait loci; siblings; speech disorders

DESCRIPTION: (provided by applicant): Speech-sound disorders are the most prevalent group of speech/language disorders in children and comprise a complex group of disorders that have a heterogeneous underlying genetic basis. The long-term goal of the project is to identify genetic influences associated with speech-sound disorders that will result in the early identification and treatment of children at risk. Three specific aims will be addressed: (1) We will identify subgroups of sibling pairs with linkage to a chromosome region(s) by employing quantitative traits associated with speech sound production and oral and written language in order to clarify genotype-phenotype relationships and elucidate genetic factors that contribute to the overlap of speech sound, language, and reading disorders. We anticipate that these subgroups will refine our classification system of speech-sound disorders to produce new genetically and phenotypically meaningful categories. (2) Collection of multigenerational pedigrees of families will allow fine mapping of the susceptibility gene(s) and refinement of genetic transmission models, including testing for parent of origin effects. (3) We will measure longitudinal changes in the phenotype and identify genetic factors contributing to these changes. This project utilizes a large cohort of well characterized nuclear families of children with speech-sound disorders (N=250; DNA available N=164 families) from our previous family study. Longitudinal follow-up of probands and siblings from these nuclear families will be conducted to describe speech-sound, language, reading, and spelling outcomes associated with linkage to various chromosome regions and developmental changes in the phenotype. Extended family members of these families will be invited to participate in the study so that multigenerational pedigrees may be constructed. Model-free linkage and transmission disequilibrium tests will examine regions of chromosome 1, 3, 6, 7, 15, 16, and 19. Identification of subgroups of speech-sound disorders associated with different chromosome regions will result in more accurate diagnostic categories and improve our understanding of the relationship of speech sound disorders to reading disorders. Therapy may be tailored to address specific cognitive deficits associated with different genetic etiologies.

描述：（由申请人提供）：语音疾病是儿童中最普遍的语音/语言障碍群，并组成了一组复杂的疾病，这些疾病具有异质性的基础遗传基础。该项目的长期目标是确定与言语疾病相关的遗传影响，这将导致对处于危险的儿童的早期识别和治疗。将解决三个具体目标：（1）我们将通过采用与语音声音生产以及口头和书面语言相关的定量性状来确定与染色体区域联系的亚组，以阐明基因型 - 表型关系，并阐明遗传因素，并阐明遗传因素，从而有助于语音，语音，语言，语言和阅读障碍和阅读障碍和阅读障碍。我们预计这些亚组将完善我们的语音疾病分类系统，以产生新的遗传和表型有意义的类别。 （2）家族多代人的收集将允许对敏感性基因进行精细映射和遗传传播模型的细化，包括测试原始效应父母。 （3）我们将测量表型的纵向变化，并确定造成这些变化的遗传因素。该项目利用了我们先前的家庭研究中的大量具有语音疾病儿童（n = 250; DNA可用n = 164个家庭）的核心核心。这些核心家族的证据和兄弟姐妹的纵向随访将进行描述，以描述与与各种染色体区域的联系相关的语音，语言，阅读和拼写结果以及表型的发展变化。这些家庭的大家庭成员将被邀请参加研究，以便可以建造多代人的血统。无模型的连锁和传播不平衡测试将检查染色体1、3、6、7、15、16和19的区域。鉴定语音疾病的亚组，与不同的染色体区域相关的言语疾病的亚组将导致更准确的诊断类别，并改善我们对阅读疾病的语音障碍的理解。治疗可以量身定制，以解决与不同遗传病因相关的特定认知缺陷。