Genetic Bases of Developmental Language Disorders

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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.