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Background and Purpose: The corpus callosum serves as a bridge to associate fibres between the two cerebral hemispheres. In placental mammals, this commissure provides for higher order neurological advantages. The molecular pathways involved in the development and pathogenesis of accallosal defects are sparse. The article reviews the current progress of studies undertaken to discern the embryological and genetic basis of the development of the corpus callosum. Sources of data: The literature, including from sources such as MEDLINE and OMIM, were subjected to searches for articles reporting findings on corpus callosum development in humans and mice. Principal findings: At least forty-six malformation syndromes and metabolic disorders have been reported in patients with complete agenesis or hypoplasia (dysgenesis) of the corpus callosum. Thirteen of these syndromes have an unknown mode of genetic inheritance, and the remaining syndromes and metabolic disorders exhibit either autosomal or X-linked inheritance among affected families. The use of patients with accallosal defects have identified mutations in at least thirty genes of the human genome, and therefore with roles implicated in the development of the corpus callosum. Patients with chromosome aberrations have been useful in defining regions on chromosomes that contain candidate genes for the development of the corpus callosum. At least eighteen different human chromosomes with numerical and/or structural aberrations have been reported in patients with acallosal defects. The mouse is an excellent model to study the structural and genetic factors that influence the development of the corpus callosum, with many similarities evident in humans. Spontaneous development of acallosal defects has been reported in at least seventeen mouse strains. Furthermore, with the use of Genetically Engineered Mice, a minimum of 15 candidate callosal agenesis genes were modeled in order to provide insightful knowledge of the molecular-structural parameters required for development of the corpus callosum. Of these mice, six had complete true agenesis of the corpus callosum, five had either true agenesis or hypoplasia of the corpus callosum, and four had hypoplasia of the corpus callosum. Conclusions: The molecular mechanisms implicated in the pathogenesis of agenesis or hypoplasia of the corpus callosum are at the verge of discovery, and are challenged by the complexity of many genes involved. Despite these barriers, findings from a complementary human-mouse model system have been helpful in understanding the genetic (molecular) causes of accallosal defects, a fascinating phenotype for over a century. [ABSTRACT FROM AUTHOR]

Current models on the etiology of psychiatric disorders support the idea of a biologic cause as well as interactions of biologic systems with the environment. The elucidation of the genetic etiology is of paramount importance to understand the cause of psychiatric disorders. Human chromosome 18 was identified as one of the first chromosomes to be aberrant in psychiatric patients and has subsequently served as a model to identify the molecular cause. In this article I review a multitude of methodologies that can be used in determining the genetic basis of schizophrenia, affective disorder and autism associated with human chromosome 18. These strategies include the use of chromosome aberrations, linkage and association studies, mouse-human comparative genomics, mutation analysis on candidate genes, trinucleotide repeat expansion studies, search for genes demonstrating parental effects and bioinformatics. Current data from the use of these methods are cited from the literature. Linkage and association studies have suggested at least 2 candidate loci on the short and long arms of chromosome 18 for each of these psychiatric disorders. Some loci are supported by the mapping of chromosome aberrations from psychiatric patients. Mutation analyses of psychiatric patients with 4 candidate genes (NEDD4L, IMPA2, PACAP and GNAL) mapping within these loci have been unsuccessful, although an association was found with the IMPA2 gene in patients with schizophrenia. With these methods and findings, our understanding of the cause of psychiatric disorders associated with human chromosome 18 has improved and will advance, especially with emerging data from the human and rodent genome projects. [ABSTRACT FROM AUTHOR]

Within the last decade, there has been sufficient evidence to support the association of epigenetic inheritance or genomic imprinting on human chromosome 14. This has been achieved with studies of imprinting on both human chromosome 14 and mouse chromosome 12, which has the largest homology to human chromosome 14. Initial studies with mouse chromosome 12 aberrations suggested that specific phenotypes due to genomic imprinting were confined to the maternal or paternal mouse chromosome 12, depending on the parent from which the chromosome was inherited. Such findings were later supplemented with human chromosome 14 aberrations that had provided evidence for imprinted intervals on this chromosome, and possibly 2 syndromes associated with a maternal or paternal uniparental disomy affecting chromosome 14. The recent discovery of 2 imprinted genes on human chromosome 14 and mouse chromosome 12 has confirmed genomic imprinting on these chromosomes. These findings will refine our understanding of the clinical consequences of human chromosome 14 aberrations and of the causes of the disease phenotype associated with defective imprinted genes. This article reviews evidence in mice and humans, and the clinical implications for genomic imprinting associated with human chromosome 14. [ABSTRACT FROM AUTHOR]