Phenotypes and familiality in speech disorders

描述（由申请人提供）：在过去的二十年中，在语音分析和语音模式识别技术方面已经取得了显著的进步，然而，这些进步对语音障碍研究竞技场的渗透已经滞后，并且实际上不存在对临床的渗透。我们建议通过调整和扩展基于隐马尔可夫模型（HMM）的语音识别技术来解决这个滞后问题，以分析来源不明的语音延迟儿童的语音。我们将证明这种方法的有效性，（a）建立有效性的建议的分析技术，在确定声学定义的类别的节段性失真（内表型），（B）检查这些声学定义的内表型的遗传性的证据和（c）寻找证据的遗传连锁所获得的内表型的3号染色体的一个区域，已牵连在言语障碍。也就是说，将解决三个目标：目标1：扩展和验证一个新的HMM为基础的方法来识别和分类的儿童谁被诊断为发展语音延迟。我们将开发一个新的信息数据库，其中包含75对5至9岁的兄弟姐妹，其中至少有一人被诊断为SD。声学语音数据和感知数据将在数据库中提供用于识别可能的内在表型的特征集。目标二：在发育性语音障碍中检查听觉和知觉的熟悉度，以确定这些测量是否定义了可遗传的数量性状。我们将使用聚类和同胞相关分析来评估声学和感知变量与更经典定义的语音变量相比的遗传性，以确定更精细的表型是否比语音遗传学研究中通常使用的表型更易遗传/更难遗传。我们假设，声学表型将定义一个可遗传的数量性状，可用于未来的基因组筛选研究，以确定参与语音的基因。目的3：评估与3号染色体的连锁在言语障碍同胞对。最近的研究显示了SD与3号染色体的着丝粒周围区域连锁的证据（Stein等人，2004年）。我们将使用定量性状连锁分析的语音，声学和感知表型，以确定是否有证据表明，在这个病人队列中，该地区的联系。

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.