Genetic Bases of Developmental Language Disorders

语言文字障碍(DSWL)是儿童中最常见的一组障碍。一个 他们中的一些人，虽然部分得到了补救，但仍然坚持到成年。我们打算调查遗传基础 俄罗斯北部偏远地区与世隔绝人群中受影响儿童的DSWL 称为OSH)和通过受影响儿童的子组确定的大的扩展家系 先驱们。由于其复杂性和大小，该谱系基本上代表了该分离物的大部分。 职业安全与健康组织成立于10世纪和11世纪，有着相对孤立的历史.目前，它包括-850 个人，其中200人是18岁以下的儿童。俄罗斯人之前确认了先驱的身份 该项目的合作者使用俄罗斯对语言和语言障碍的诊断方案 对所有18岁及以下的儿童进行评估。在130名接受评估的儿童和青少年(7-18岁)中，95人 (-73%)临床诊断为不同类型的DSWL。此外，尽管没有临床诊断， 许多儿童在言语和与语言有关的领域(如发音、阅读、写作、 语音加工)。在评估的25名幼儿(2-6岁)中，17名有发音困难和 表现出语言延迟和/或障碍。在60名与确诊儿童有关的受评成年人中， 45显示了与DSWL有关的各种缺陷。家谱和人种学表明，OSH 是由5-7个人创立的，那里大约80%的人有各种不同的亲戚 学位。该种群在遗传上是同质的，是近亲交配的，但其特点是高度 整个基因组的遗传变异，使其适合于遗传分析。我们的俄罗斯合作者已经 一直在收集职业安全局居民的DNA样本。目前，已建立了404个细胞系，487个 从没有可用的细胞系的全血标本中提取的DMAS，以及从 口腔拭子。我们在这里建议(1)仔细描述OSH中传递的表型 家系；(2)进行复杂的多变量分析，以了解DSWL的传播模式；以及 (3)对选定的OSH家系的核分支进行全基因组采样分析 在至少三代人中包含多个受影响的个体。

Disorders of spoken and written language (DSWLs) are the most prevalent group of disorders in children. A number of them, although partially remediated, persist in adulthood. We intend to investigate genetic bases of DSWLs in affected children in an isolated population in a remote area of Northern Russia (hereafter referred to as OSH) and a large extended pedigree ascertained through a subgroup of affected child probands. Because of its complexity and size, the pedigree essentially represents the majority of the isolate. Established in the 10th and 11 th centuries, OSH has a history of relative isolation. Currently, it includes -850 individuals, -200 of whom are children under age 18. Probands were previously identified by Russian collaborators on the project, using Russian diagnostic schemes for speech and language impairments in an evaluation of all children 18 and younger. Of 130 assessed children and adolescents (aged 7-18), 95 (-73%) were diagnosed clinically with a variety of DSWLs. In addition, although not clinically diagnosed, many children had deficits in speech and language-related domains (e.g., pronunciation, reading, writing, phonological processing). Of 25 young children (aged 2-6) assessed, 17 had difficulties in pronunciation and exhibited language delays and/or impairments. Of the 60 evaluated adults related to the diagnosed children, 45 demonstrated various deficiencies related to DSWLs. Genealogical and ethnographical suggest that OSH was founded by 5-7 individuals, and that approximately 80% of the people there are relatives of various degrees. The population is genetically homogeneous and inbred, but is characterized by a high degree of genetic variation across the genome, making it suitable for genetic analyses. Our Russian collaborators have been collecting DNA samples from OSH residents. Currently, 404 cell lines have been established, 487 DMAs extracted from whole blood specimens without an available cell line, and 47 DMAs extracted from buccal swabs. We here propose to (1) carefully characterize the phenotypes transmitted in the OSH pedigree; (2) carry out complex multivariate analyses to understand the transmission patterns of DSWL; and (3) conduct whole-genome sampling analyses on selected nuclear branches of the OSH pedigree that contain multiple affected individuals in at least three generations.