A complex disease is one in which multiple genetic and environmental factors contribute to the development of the disorder. The identification of the molecular basis of complex diseases remains a crucial step in the understanding of the most common human diseases. The identification of the genes that are involved in complex diseases requires the development of new different approaches, including the development of new methods for mutation detection, as well as the optimization of existing methods. Understanding the role of specific genes in complex diseases requires the availability of sensitive and efficient methods for the detection of mutations in specific genes. Therefore, we have sought to optimize the single-stranded conformation polymorphism method and determine the efficiency of the method. For many types of cancers a small percentage of the cases are due to an inherited form of the disease. Analysis of patients with von Hippel-Lindau disease has enabled a number of mutations in the gene to be identified and correlations made between clinical characteristics and mutation type. Basal cell carcinomas are a form of skin cancer and represent the most common human malignancy. Patients with the nevoid basal cell carcinoma syndrome (NBCCS) have multiple basal cell carcinomas as well as certain developmental defects. Genetic mapping and physical mapping techniques have been employed to generate a detailed map of the NBCCS region. Sequencing of clones in this region has identified a new member of the zinc finger family of transcription factor genes. One of the limitations of current approaches to identify disease genes is the ability to rapidly find genes in the region of analysis. Many genes are preceded by CpG-rich stretches of DNA, which frequently contain Not I restriction sites. It has been shown that sequences surrounding Not I sites are highly enriched for transcribed sequences. A panel of Not I-containing clones on chromosome 3 has been used to identify expressed sequences in a region commonly deleted in lung tumors, and in renal cell carcinomas. One of these genes is a new member of the mitogen-activated protein kinase-activated protein (MAP) family of MAP kinases.
