Genetic Bases of Developmental Language Disorders

口语和书面语言障碍（DSWLs）是儿童中最常见的一组障碍。一 其中一些虽然得到部分补救，但在成年后仍然存在。我们打算研究基因基础 在俄罗斯北方偏远地区的一个孤立人群中，受影响儿童的DSWL（以下简称DSWL 称为奥什）和通过受影响儿童亚组确定的大范围谱系 先证者由于其复杂性和规模，谱系基本上代表了大多数分离株。 奥什建立于10世纪和11世纪，有一段相对孤立的历史。目前，它包括-850 其中200人是18岁以下的儿童。先证者先前由俄罗斯人确定 该项目的合作者，使用俄语诊断方案的语音和语言障碍， 对所有18岁及以下儿童进行评估。在接受评估的130名儿童和青少年（7-18岁）中， (-73%）临床诊断为各种DSWL。此外，虽然没有临床诊断， 许多儿童在言语和语言相关领域（例如，发音，阅读，写作， 语音处理）。在25名接受评估的幼儿（2-6岁）中，17名有发音困难， 表现出语言延迟和/或障碍。在接受评估的60名与确诊儿童相关的成年人中， 45例表现出与DSWLs相关的各种缺陷。家谱和人种学研究表明，奥什 是由5-7个人成立的，大约80%的人有各种各样的亲戚 度该种群是遗传同质和近亲繁殖的，但其特点是高度的 整个基因组的遗传变异，使其适合遗传分析。我们的俄国合作者 一直在收集奥什居民的DNA样本目前已建立细胞系404个，487个 从没有可用细胞系的全血标本中提取的DMA，以及从 口腔拭子。我们在这里建议（1）仔细描述在奥什中传播的表型 （2）进行复杂的多变量分析，以了解DSWL的传播模式;以及 (3)对奥什家系的选定核分支进行全基因组取样分析， 在至少三代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.