Genetic Bases of Developmental Language Disorders

发育性语言障碍的遗传基础

• 批准号: 7588720
• 负责人: ELENA L GRIGORENKO
• 金额: $ 58.98万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-15 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7588720
• 关键词: Address; Adolescent; Adult; Affect; Age; Architecture; Area; Behavioral; Blood specimen; Breeding; Candidate Disease Gene; Cell Line; Child; Chromosome Deletion; Chromosome Mapping; Chromosome abnormality; Complex; Computer software; Consent; Copy Number Polymorphism; Cross-Sectional Studies; Cytogenetics; DNA; Data; Data Files; Development; Diagnosis; Diagnostic; Disease; Epigenetic Process; Etiology; Evaluation; Exhibits; Frequencies; Generations; Genes; Genetic; Genetic Techniques; Genetic Variation; Genome; Genomics; Genotype; Impairment; Incidence; Individual; Language; Language Delays; Language Development Disorders; Language Disorders; Linguistics; Methods; Methylation; Molecular Genetics; Multivariate Analysis; Nature; Nuclear; Nuclear Family; Other Genetics; Outcome; Pattern; Phenotype; Population; Population Genetics; Process; Reading; Recording of previous events; Relative (related person); Research; Research Design; Research Personnel; Risk Factors; Russia; Sampling; Scheme; Severities; Signal Transduction; Speech; Staging; Structure; Subgroup; Swab; Techniques; Whole Blood; Work; Writing; aged; base; design; follow-up; genetic analysis; genetic pedigree; genetic profiling; genome-wide; impression; interest; meetings; member; phonology; proband; programs; segregation; success; trait; transmission process

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.

口语和书面语言疾病（DSWL）是儿童中最普遍的疾病。一个 他们的数量虽然进行了部分修复，但在成年期间持续存在。我们打算研究遗传基础 在俄罗斯北部偏远地区，受影响儿童中的DSWL的DSWL（以后 被称为osh），通过受影响的儿童子组确定了大型的延长血统 概率。由于其复杂性和大小，血统基本上代表了大多数分离株。 OSH建立在10世纪和11世纪，具有相对隔离的历史。目前，它包括-850 个人，其中-200岁的儿童18岁。先前通过俄罗斯识别出来 该项目的合作者，使用俄罗斯诊断方案来解决语音和语言障碍 评估所有18岁及以下的儿童。在130名评估儿童和青少年（7-18岁）中，95 （-73％）在临床上被诊断为各种DSWL。另外，尽管未被诊断出临床诊断，但 许多孩子在语音和语言有关的领域缺陷（例如，发音，阅读，写作， 语音处理）。在评估的25名幼儿（2-6岁）中，有17个发音和 表现出语言延迟和/或障碍。在与被诊断儿童有关的60名评估成人中， 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个人建立的，大约80％的人是各种亲戚 学位。人口在遗传上是同质和近交的，但其特征是高度 整个基因组的遗传变异，使其适用于遗传分析。我们的俄罗斯合作者有 一直从OSH居民那里收集DNA样品。目前，已经建立了404条细胞系，487 从没有可用细胞系的全血样本中提取的DMA，从47个DMA中提取 颊拭子。我们在这里建议（1）仔细表征OSH中传播的表型 谱系; （2）进行复杂的多元分析，以了解DSWL的传输模式；和 （3）对OSH血统的选定核分支进行全基因组抽样分析 在至少三代中包含多个受影响的人。