PAX6 Lab Report
Our planet is blessed with biodiversity composed of prokaryotes and eukaryotes. Almost all of them have specialized systems of sensing light, sensory and/or motor response composed of a cell, tissue or organ like eyes and brain. The Pax (Paired box) genes and proteins have been observed critical during formation of such tissues or organs and Pax family transcriptional regulators remain critical to maintain their functional anatomy. The Paired Box 6 (Pax6) best exemplifies the conservation of functions through evolution. The importance of Pax6 was established by the work on Drosophila mutant lines which failed to develop eyes, and described as “eyeless” (ey) phenotype. It is present on chromosome 4 of Drosophila melanogaster and serves as a
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The analysis of reports through human PAX6 Allelic Variant Database (Brown et al., 1998) suggests that more than two third of mutations are associated with congenital eye malformations. Mutations in the PD have been described well but on the HD and transactivation region are highly limited (Singh et al., 2001; D’ Elia et al., 2006). The structure–function relationship of wild-type PAX6 and its alternatively spliced isoform, PAX6(5a) indicates that the mutation induced changes are not only confined to the place of mutation but they are dispersed due to conformational changes induced by missense mutations (Shukla and Mishra, 2011). It is also interesting to note that due to a single mutation several contacts are destroyed and many new contacts are introduced which is likely due to space constraints or by some force constraints. The alteration in the contact residues of the PAX6 influences modulation in DNA binding and other cellular interactions due to variation in the state of the residues involved in the formation of secondary structure (helix, sheet, turns and coils) of the PAX6 (Shukla and Mishra, 2012). It is proposed that the mutation induced structural, and conformational changes, may disturb the interaction of the regulatory molecules (like miRNAs, upstream regulators and interacting partners) to Pax6 itself and also the interaction of Pax6 to its downstream targets (Shukla and Mishra, 2012). Therefore, it is presumed to be the cause or effect of variable penetrance and expressivity of phenotypes because PAX6 and PAX6(5a) mutants may differentially interact with tissue-restricted proteins of the transcriptional
The analysis of reports through human PAX6 Allelic Variant Database (Brown et al., 1998) suggests that more than two third of mutations are associated with congenital eye malformations. Mutations in the PD have been described well but on the HD and transactivation region are highly limited (Singh et al., 2001; D’ Elia et al., 2006). The structure–function relationship of wild-type PAX6 and its alternatively spliced isoform, PAX6(5a) indicates that the mutation induced changes are not only confined to the place of mutation but they are dispersed due to conformational changes induced by missense mutations (Shukla and Mishra, 2011). It is also interesting to note that due to a single mutation several contacts are destroyed and many new contacts are introduced which is likely due to space constraints or by some force constraints. The alteration in the contact residues of the PAX6 influences modulation in DNA binding and other cellular interactions due to variation in the state of the residues involved in the formation of secondary structure (helix, sheet, turns and coils) of the PAX6 (Shukla and Mishra, 2012). It is proposed that the mutation induced structural, and conformational changes, may disturb the interaction of the regulatory molecules (like miRNAs, upstream regulators and interacting partners) to Pax6 itself and also the interaction of Pax6 to its downstream targets (Shukla and Mishra, 2012). Therefore, it is presumed to be the cause or effect of variable penetrance and expressivity of phenotypes because PAX6 and PAX6(5a) mutants may differentially interact with tissue-restricted proteins of the transcriptional