Ocular coloboma is a genetic disease characterized, phenotypically, by an abnormal appearance of the iris. When the PAX6 gene (responsible for the development of the precursor lens of the eye) is mutated, it can cause ocular coloboma by not allowing effective closure of the embryonic optic cup fissure (O'Neill et al 1986). The PAX6 gene is located on the P arm of the eleventh chromosome (11p13) and is part of a protein complex called the paired box gene family (OMIM 2013). PAX6 is responsible for many different things during fetal development, related to the brain, spinal cord and pancreas. Ocular coloboma can also occur with various other disorders, such as mental retardation, absence of corpus callosum, etc., due to the volume of neuronal tissue that PAX6 is responsible for developing (OMIM 2013). The cause of ocular coloboma is not well understood. This is most likely an autosomal dominant mutation in the PAX6 gene, with some research supporting autosomal recessive inheritance. Some research also supports a dominant negative mutation. A dominant negative mutation is a gain-of-function mutation and is extremely rare (OMIM 2013). These types of mutations usually result in some form of cancer, and the one that causes ocular coloboma occurs in about one in 10,000 people. PAX6 functions to target genes via a paired-end DNA binding domain, made up of two linking domains. subdomains; one is an N-terminal subdomain and the other is a C-terminal subdomain. In humans, the PAX6 gene is responsible for two alternatively spliced ​​isoforms, each with a unique composition like that of the paired domain (OMIM 2013). This paired-end binding domain allows exon 5a to function...... middle of paper ......75. PDF.Herpin, A., Lelong, C. and Favrel, P. (2004) Transforming growth factor beta-related proteins: an ancestral and widespread superfamily of cytokines in metazoans. Developmental and Comparative Immunology, 28, 461-485. Accessed April 1, 2014, from http://www.ncbi.nlm.nih.gov/pubmed/15062644Jonathan A. Epstein, Tom Glaser, Jiexing Cai, Lisa Jepeal, David S. Walton, and Richard Maas. "Two independent and interacting DNA-binding subdomains of the Pax6 paired domain are regulated by alternative splicing." Genes and development (1994): 2022-2034. PDF. O'Neill, M.J.F., McKusick, V.A., Kniffin, C.L., Kelly, J. (1986). Ocular coloboma. Online Mendelian inheritance in humans, , . Retrieved from http://omim.org/entry/120200?search=ocular%20coloboma&highlight=ocular%20coloboma#contributors-shutterOMIM. PAIRED BOX GENE 6; PAX6. September 26, 2013. Website. March 19 2014.