The human/mouse homology map provides an excellent tool to identify candidate genes involved in human disease. Studies have been initiated using several newly identified loci in man that are candidates for involvement in facial clefting. In collaboration with our colleague at the University of Arizona, we have used markers for homologous positions in the mouse to search for QTLs that affect facial clefting induced by various teratogens. In order to conduct this research, it has been necessary to develop new statistical methods suitable for the analysis of categorical data (i.e., cleft affected or not) in a recombinant inbred line breeding design. These methods were applied to datasets on the teratogens 6-aminonicotinamide which mimics the effects of smoking and dilantin (phenytoin) which is taken as an anti-seizure drug by many pregnant women and is strongly suspected to cause clefting in humans. Our analyses identified several chromosomal regions of the mouse genome that are likely to contain clefting susceptibility genes. Some of these include candidate genes such as collagen or developmental regulators of the homeobox families. Further mapping studies in this mouse model are being planned to validate these findings and to narrow down the regions of the mouse genome that may contain these clefting susceptibility genes. These regions may be isolated to the point where DNA sequencing or transgenic approaches will be appropriate to identify the specific genes involved in the process.
