DESCRIPTION AND FUNCTIONAL IMPLICATIONS OF A NOVEL MUTATION IN THE SEX-DETERMINING GENE SRY

The sex determining gene SRY was screened for molecular alteration in an XY sex reversed female by single-strand conformation polymorphism (SSCP) technique, An A-to G transition was detected which leads to an exchange of a tyrosine by a cysteine in the SRY protein. The affected tyrosine residue located at the C terminus of the DNA binding protein is evolutionarily strongly conserved among the members of the HMG box containing proteins. Using gel shift assay and peptide synthesis such a mutation is shown to abolish the SRY protein DNA binding ability. The involvement of this particular amino acid in the binding specificity is also discussed. (C) 1994 Wiley-Liss, Inc.