April 25, 2007
In the search for genes that contribute to nonsyndromic cleft lip and/palate, scientists once followed the long road. They performed lengthy and always complex linkage analyses of DNA from large families and populations of people with histories of this common birth defect. But in recent years, the scientists have begun to pursue a more technologically direct road. They collect the DNA samples per usual but now directly sequence certain genes suspected of contributing to cleft lip and/or palate. A few years ago, NIDCR grantees and colleagues used this approach with the MSX1 gene and identified mutations that might account for 2 percent of cleft lip and/or palate cases. In 2005, they sequenced 20 genes and found mutations that contribute to 6 percent of cases. Now, in the March 13 issue of the Proceedings of the National Academy of Sciences, the scientists sequenced the coding regions of 12 members of the fibroblast growth factor (FGF) and FGF receptor gene families and found seven mutations that may contribute to as much as 5 percent of nonsyndromic cleft lip and/or palate. The group followed up its findings by generating three-dimensional computer models of the FGF proteins that predicted how the altered amino acids would affect their normal shape and function.