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Abstract #15331 Published in IGR 1-3
A cellular assay distinguishes normal and mutant TIGR/myocilin protein
Zhou Z; Vollrath DHuman Molecular Genetics 1999; 8: 2221-2228
Glaucoma is a blinding eye disease that affects (similar) 70,000,000 people world-wide. Mutations in the gene TIGR/MYOC have been shown to cause the most common form of the disease, primary open angle glaucoma, in selected families. Amino acid sequence variants of the gene have been found in 2-4% of sporadic primary open angle glaucoma cases. Most variants are rare and it is often difficult to definitively distinguish between a deleterious mutation and a benign variant solely on the basis of relative frequencies in patient and control groups. The function of the TIGR/myocilin protein is unknown and an assay to functionally classify variants is lacking. The authors sought to develop a biochemical assay to distinguish different forms of TIGR/myocilin. They investigated the Triton X-100 detergent solubility characteristics of mutant and normal forms of the protein, expressed by transfection in cultured cells. They observed a clear difference in the behavior of the two types of TIGR/myocilin; all confirmed mutant proteins tested were substantially Triton insoluble, while normal protein and controls were completely soluble. The authors also tested seven ambiguous variant proteins and classified them as mutant or normal on the basis of their Triton solubility. The results in some cases validated, and in other cases contradicted, earlier classifications of these variants. To the authors' knowledge, Triton solubility is the first example of a general difference in the properties of mutant and normal forms of TIGR/myocilin. The assay they have developed will be useful for discerning protein functional information from the location of mutations, will aid genetic counselling of individuals with TIGR/myocilin variants and may provide a clue to understanding a mechanism by which mutations in TIGR/MYOC cause glaucoma.
Dr. D. Vollrath, Department of Genetics, Stanford University School Medicine, Lane Building, 300 Pasteur Drive, Stanford, CA 94305-5120; USA
Classification:
1.2 Population genetics (Part of: 1 General aspects)
