Genetic Deficiencies
Another major interest of the Center is to identify the genetic causes of both common and diseases of connective tissues such as bone and cartilage. The Center staff was among the first to show that mutations in collagen genes can carry mutations causing diseases of bone and cartilage. Their interest in collagen genes was based on a large background of work they and others had done on the structure and function of the proteins and their biosynthesis. Members of the Center staff and their previous associates isolated the first gene for a series of human collagens. They then used the genes to find mutations that caused osteogenesis imperfecta and severe disorders of cartilage that cause dwarfism and associated problems (Stickler syndrome, spondyloepiphyseal dysplasia, and achondrogenesis type II, Kniest dysplasia). They went on to find mutations in collagen genes that caused the defects in a subset of patients with osteoporosis, a subset of patients with early onset osteoarthritis, and a subset of patients with aortic aneurisms that were prone to rupture. The Center found mutations in collagen genes that cause or predispose sciatica because of intervertebral disk herniation.

The genes in which these mutations have been found are complex and the identification of the mutations has in part depended on technology developed by the Center staff for rapid scanning of genes for mutations, a technology known as conformation sensitive gel electrophoresis (CSGE). The DNA diagnostic tests for these and other diseases are being developed for several reasons. One is that a definitive diagnosis as to cause of a disease is frequently an important guide as to which existing therapies or changes in expectations or lifestyle may help the patient. The second reason is that knowing the exact cause of a disease is frequently the first step in developing new therapies, such as gene therapy, that may provide a cure for previously untreatable diseases.

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