Evolutionary Analysis of Disease-Associated Mutations of Fibroblast Growth Factor Receptor 3 Gene (FGFR3 Gene)

The central focus of this research is to achieve a better understanding of the genetics of disease and provide assistance with the identification of disease-associated genes. Information from interspecific alignments can indicate amino acid residues in gene products that are likely to produce disease if mutated in humans. We analyzed disease mutation data and homologous gene sequences for one disease-associated human gene: Fibroblast Growth Factor Receptor 3 (FGFR3). This protein is important for the cellular processes such as the regulation of cell growth and division, formation of blood vessels, and others. The FGFR3 gene is located on the short (p) arm of chromosome 4 at position 16.3. In this study we determined the association between the prevalence of disease mutations and the extent to which corresponding amino acid sites in other species have been conserved throughout evolutionary history. Using available information from online databases, we obtained data for single base pair replacement mutations observed in FGFR3 gene. The elimination of frequency information prevents bias in our results towards the properties of commonly observed mutations over those less frequently reported for a specific genetic disease. In humans mutations are more abundant than another species. The disease-associated amino acid changes are overabundant at conserved residues. Chemical differences of these disease-associated amino acid changes are more radical than the commonly encountered polymorphic amino acid variation found in humans or permitted by natural selection throughout evolutionary history.