This web page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison.
CTLA4 Gene
Figure 1: Gene structure of CTLA4 showing known polymorphisms
The CTLA4 gene is a member of the immunoglobulin superfamily, encoding a protein receptor that transmits an inhibitory signal to T cells. The human CTLA4 gene spans 6,175 bases on the q arm of chromsome 2 (2q33), consisting of four exons. The fist exon encodes a leader sequence, the second an immunoglobulin V-like domain, the third a hydrophobic trans-membrane region, and the fourth a cytoplasmic domain [1]. Alternate transcriptional splicing can result in varying isoforms. The membrane-bound isoform functions as a homodimer interconnected by a disulfide bond, while the soluble isoform functions as a monomer [2].
There are several polymorphisms of the gene that can affect the Tcell-effector activity of the gene. In particular, the A49G dimorphism resulting in a threonine/alanine peptide exchange has been linked to Grave’s disease in the majority of populations. This polymorphism leads to the expression of a defective receptor, so the inhibitory effect of the receptor on T cell activation is impaired [3].
There are several polymorphisms of the gene that can affect the Tcell-effector activity of the gene. In particular, the A49G dimorphism resulting in a threonine/alanine peptide exchange has been linked to Grave’s disease in the majority of populations. This polymorphism leads to the expression of a defective receptor, so the inhibitory effect of the receptor on T cell activation is impaired [3].
References
[1] Chistiakov D., Turakulov R., (2003). CTLA-4 and its role in autoimmune thyroid disease. J Mol Endocrinol, 31, doi: 10.1677/jme.0.0310021
[2] Valk E. Rudd C. Schneider H. 2008. CTLA-4 trafficking and surface expression. Trends in Immunology, 29, 272-279. doi:10.1016/j.it.2008.02.011
[3] Pastuszak-Lewandoska D., Sewerynek E., Domańska D., Gładyś A., Skrzypczak R., Brzeziańska E. (2012) CTLA-4 gene polymorphisms and their influence on predisposition to autoimmune thyroid diseases (Graves’ disease and Hashimoto's thyroiditis). Arch Med Sci, 8(3). doi: 10.5114/aoms.2012.28593