Cytogenetic abnormalities, which can include trisomy, mosaicism, or chromosome rearrangements (such as translocation, terminal deletions, interstitial deletions, or interstitial duplications) account for approximately 20 percent of mental retardation.  Chromosome abnormalities also account for a substantial amount of morbidity and moirtality, especially among children.  Among the conditions that the Branch studies in this area are Prader-willi syndrome, Angelman syndrome, Williams syndrome, Down syndrome, Cornielia de Lange syndrome, Smith-Magenis syndrome, and X chromosome disorders, such as Rett syndrome and Fragile X syndrome. 

Genetics and Genetic Disorders--Genetic or genetically influenced conditions are among the leading causes of organically-based mental retardation. Down syndrome and Fragile X syndrome, both involving major chromosomal defects, are of particular research interest, as are single gene defects like phenylketonuria and conditions of polygenic origin, such as neural tube defects and autism.

Molecular Biology And Molecular Genetics--Basic knowledge of the structure and organization of the human genome is essential if the basic molecular defects of conditions that are associated with mental retardation and other forms of developmental disabilities are to be understood. Eventually, such knowledge will contribute to the development of non-invasive or non-destructive methods of primary prevention. Projects dealing with cloning, mapping and organization of genes, and gene transfer into cells, mammalian embryos, and whole animals are encouraged.

Developmental Neurobiology--Major areas that merit research attention include the pathway of differentiation followed by CNS cells; axon outgrowth and target recognition; hormonal and other factors that influence neuronal development, differentiation, and survival; neuroplasticity; factors that contribute to neuronal cell death or degeneration; and neuronal transplantation.

Pathophysiology of Mental Retardation--The Branch sponsors studies to identify the mechanisms of action of the various factors leading to mental retardation and other developmental disabilities. Studies on how a disorder produces its clinical manifestations are directly relevant to its eventual prevention and treatment. The Branch is interested in studies on developmental, neurobiological, morphological, histological, and ultrastructural aspects of the central nervous system, as well as sensory defects and their relation to learning and development.

Prevention and Amelioration--Gene mapping activities and application of recombinant DNA methods allow isolation of a variety of highly specific human genes. Further advances may lead to new treatments for genetic disorders.

The Branch is interested in development of less invasive techniques for prenatal diagnosis, improved methods of fetal therapy, and development of new biological agents, including vaccines.