Mental retardation (MR) is a common condition affecting about 2-3% of the human population. It reflects a diversity of potential causes that include both genetic and environmental factors. The causation in at least half of all MR cases is still unknown. The genetic component of MR, which consists of chromosome aberrations (approximately 12%), single gene defects (approximately 10%) and multi-factorial effects (approximately 10%), is likely due to defects in a large number of autosomal and X-linked genes. The goal of this proposal is to identify, clone, and characterize a selected set of genes involved in brain development and function, which, when defective, cause mental retardation. The long-term objective of our research is to aid in the understanding of brain development and function that play a role in cognitive learning abilities. The characterization of disease-associated translocation breakpoints has proven to be a productive strategy to identify the genes responsible for specific disorders. We have identified several patients with balanced chromosome translocations (X; autosome and autosome; autosome) and MR.
The Specific Aims of this proposed research are designed to 1) fine map the translocation breakpoints delineating potential MR loci, 2) identify and isolate the genes, associated with the translocation breakpoints, and 3) characterize and confirm the identify of the MR genes and 4) as an extension of the proposed work, to elucidate the role of encoded proteins in brain development and function. Identification and characterization of the genes involved should be a major advance in the understanding of brain functions critical for development of intellectual and learning abilities as well as facilitating objective diagnosis.
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