Cloning of Genes with High Homology to the Faciogenital Dysplasia (FGD1) Gene; The Human FGD2, Mouse FGD2, and Zebra Fish FGD1 Genes
Faciogenital dysplasia (FGDY), also known as Aarskog-Scott syndrome, is an X-linked developmental disorder characterized by disproportionately short stature and by facial, skeletal, and urogenital anomalies. Molecular genetic analysis mapped FGDY to chromosome Xp11.21 (Gorski et al., 1992), and the gene responsible for FGDY, FGD1, was isolated (Pasteris et al., 1994). Recently, the murine homologue of FGD1 (Fgd1) was isolated and mapped to the mouse X chromosome (Pasteris et al., 1995). Preliminary cross-hybridization experiments suggested that there may be at least two other genes in the genome with sequences very similar to FGD1. Based on these observations, we have cloned both a human and a murine homologue (HFgd2 and MFgd2, respectively), and a zebra fish homologue (ZFgd1). A novel application of polymerase chain reaction was developed which takes advantage of the high degree of sequence homology between parts of these genes in three developmentally relevant organisms. Comparative analysis of the new sequences shows each isolated homologue to be potential members of the GEF family of proteins. In each of these isolated genes, variation within the size of the introns is observed. Further support of this finding includes remarkable fidelity of conserved amino acid residues as well as a wide range of tissue expression. Through future investigation of these new clones, we hope to better elucidate the roles of GEFs, particularly the FGD family, in human, murine, and zebra fish signal transduction and development. These new genes will also provide more avenues through which to study the clinical phenotype of human Faciogenital Dysplasia.