Phenotypes and familiality in speech disorders

言语障碍的表型和家族性

• 批准号: 7038247
• 负责人: H TIMOTHY Bunnell
• 金额: $ 15.56万
• 依托单位: ALFRED I. DU PONT HOSP FOR CHILDREN
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7038247
• 关键词: clinical research; computer system design /evaluation; developmental disease /disorder; family genetics; human subject; information systems; linkage mapping; middle childhood (6-11); phenotype; phonology; quantitative trait loci; siblings; speech disorders; speech recognition

DESCRIPTION (provided by applicant): Over the past two decades, significant advances have been made in speech analysis and speech pattern recognition techniques, however, the penetration of these advances into the speech disorders research arena has lagged, and penetration into the clinic is virtually non-existent. We propose to address this lag by adapting and extending speech recognition technology based on Hidden Markov Modeling (HMM) to an analysis of speech from children with speech delay of unknown origin. We will demonstrate the efficacy of this approach by (a) establishing the effectiveness of the proposed analysis techniques in identifying acoustically defined categories of segmental distortions (endophenotypes), (b) examining these acoustically-defined endophenotypes for evidence of heritability and (c) searching for evidence of genetic linkage of the obtained endophenotypes to a region of chromosome 3 that has been implicated in speech disorders. That is, three aims will be addressed: Aim 1: Extension and validation of a new HMM-based approach to the identification and classification of children who are diagnosed with developmental phonological delays. We will develop a new database of information associated with 75 five to nine year old sibling pairs, at least one of whom is diagnosed with SD. Acoustic speech data and perceptual data will provide feature sets in the database for use in identifying possible endophenotypes. Aim 2: Examination of familiarity of acoustic and perceptual measures in developmental phonological disorders to determine whether these measures define heritable quantitative traits. We will assess heritability of the acoustic and perceptual variables as compared with more classically defined speech variables using cluster and sibling correlation analysis to determine whether the more refined phenotypes are more/less heritable that those typically used in speech genetics studies. We hypothesize that the acoustic phenotypes will define a heritable quantitative trait that can be used for future genome screening studies to identify genes involved in speech. Aim 3: Assessment of linkage to chromosome 3 in speech-disordered sibling pairs. Recent studies have shown evidence for linkage of SD to the pericentromeric region of chromosome 3 (Stein et al., 2004). We will use quantitative trait linkage analyses for the speech, acoustic and perceptual phenotypes to determine whether there is evidence for linkage to this region in this patient cohort.

描述（由申请人提供）：在过去的二十年中，语音分析和言语模式识别技术已取得了重大进展，但是，这些进步的渗透到语音障碍研究领域落后于言语障碍，并且渗透到诊所中实际上是不存在的。我们建议通过根据隐藏的马尔可夫建模（HMM）调整和扩展语音识别技术来解决这一滞后，以分析来自未知来源的语音延迟的儿童的言语。我们将通过（a）确定所提出的分析技术在确定节段扭曲的声学定义类别（内型型（内跨表型）中，（b）检查这些声学定义定义的内类型型的遗传性和（c）搜索遗传学上的遗传学的遗传链接的证据，以搜索这些遗传性的遗传型的证据，该领域的有效性是为了确定该方法的有效性语音障碍。也就是说，将解决三个目标：目标1：扩展和验证基于HMM的新方法，以识别和分类被诊断为发育语音延迟的儿童。我们将开发一个与75五到九岁的兄弟姐妹对相关的新信息数据库，其中至少一个被诊断出患有SD。声音数据和感知数据将在数据库中提供特征集，以识别可能的内型型。目标2：检查发育语音障碍中声学和感知度量的熟悉程度，以确定这些措施是否定义了可遗传的定量特征。与使用群集和兄弟姐妹相关性分析更经典定义的语音变量相比，我们将评估声学和感知变量的遗传力，以确定较精炼的表型是否更/较少的遗传性比语音遗传学研究中使用的表型是否更小。我们假设声学表型将定义一个可遗传的定量特征，该特征可用于未来的基因组筛查研究以识别涉及语音的基因。 AIM 3：评估与语音序列兄弟姐妹对中染色体3的联系。最近的研究表明，SD连接到3染色体3的周围玻璃粒区域的证据（Stein等，2004）。我们将对语音，声学和感知表型使用定量性状链接分析来确定是否有证据表明该患者队列中的该区域有联系。