The overall goal of the proposed research is to investigate issues pertaining to genetic etiology of specific developmental language impairment (LI), using both family and molecular genetic designs. Specifically, we aim to use case-control family research designs to determine whether there is significant family aggregation of processes associated with developmental language impairment amongst the primary relatives (biological parents, siblings) of LI children and, if so, whether the rates and patterns of expression are compatible with any known mode(s) of genetic transmission. A further goal of this research is to investigate whether temporal processing disorder meets the criteria as a """"""""biological trait marker,"""""""" which could be used for classifying family members of LI probands (especially adults) as affected or unaffected in molecular genetic studies. This is a crucial, but currently limiting, step necessary for gene-linkage studies. Finally, we propose a series of molecular genetic studies aimed at establishing gene linkage for LI. Two converging family genetic research strategies are proposed. First, using a case-control family design, 1) to determine whether the primary relatives of LI children differ significantly on a selected battery of speech, language, temporal processing and reading measures from the primary relatives of matched control children; 2) to determine whether speech, language, reading and/or temporal processing disorders aggregate within the families of Ll probands, and if so, whether the rates and patterns of expression are compatible with any known mode(s) of genetic transmission; and 3) to determine whether temporal processing disorder may represent a """"""""biological trait marker"""""""" for developmental language disorder. Next, conducting a genome-wide scan with highly polymorphic DNA markers, analyzed with parametric and non-parametric methods, to search for linkage to a major genetic locus (or loci) involved in the etiology of developmental language disorder. It is widely recognized that developmental language disorders appear to run in families. However, the contribution of genetic and/or environmental influences on these developmental disabilities has not been established, whereas, behavioral family studies allow the use of patterns of familial aggregation of disease or disability to infer mode(s) of genetic transmission, empirical demonstration of genetic transmission must rely on molecular genetic studies. This proposal represents the convergence of these research methodologies for the purpose of studying issues pertaining to the genetic basis of specific developmental language impairment. We build upon the sample already identified in the initial phase of this family study to provide suitable extended families for gene linkage studies.
