Project Summary/Abstract Specific language impairment (SLI) affects up to 7% of individuals in the United States. SLI affects communica- tion, learning, and social abilities, and requires additional attention in school. The causes of SLI are not known. However, twin studies and family studies clearly demonstrate that there are genetic components involved in the transmission of this disorder. There have been several linkage studies of small, outbred SLI families, but to date these studies have had limited success identifying causative genes for this disorder. Very few attempts were made to report SLI loci in extended families with independent replication. There is a need for further focus on a family-based approach, specifically using consanguineous families, to detect SLI loci that can allow us to identify causative genes. The long-term objectives of the proposed study are to identify genes responsible for SLI by studying consanguineous families ascertained from Pakistan. Recently, a similar approach was used, which identified the first gene responsible for stuttering, another phenotypically and genetically complex disor- der. We initially performed genetic analysis in 14 consanguineous SLI families in Pakistan. Our preliminary linkage mapping in SLI families suggested SLI loci, which is a proof of principle, but it also demonstrated the need to extend gene-mapping and phenotyping in additional SLI families from Pakistan. We propose three specific aims to achieve. Age appropriate means and standard deviations will be calculated in Pakistani sam- ples for multiple language assessments (Aim#1). Genome-wide gene mapping will be performed in well char- acterized multigenerational consanguineous SLI families (Aim#2). The frequency of common homozygosity regions will be estimated in Pakistani samples (Aim#3).