MATRIX-ASSISTED LASER DESORPTION IONIZATION TIME-OF-FLIGHT MASS-SPECTROMETRY AS A RAPID SCREENING METHOD TO DETECT MUTATIONS CAUSING TAY-SACHS-DISEASE/

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-M S) has been used as a rapid method for the detection of human genetic polymorphisms. In particular, the mutations in the human HEXA gene tha t cause the infantile Tay-Sachs disease have been studied using MALDI- MS to demonstrate the feasibility of this technique for use in clinica l and diagnostic analysis. The protocols involved in this approach inc lude, polymerase chain reaction for the amplification of the mutation site from buccal cell DNA, followed by restriction enzyme digestion of the amplified regions of the template cells. The products of amplific ation and digestion were studied using MALDI-MS. MALDI-MS experiments are shown to provide essentially the same information as obtained from gel electrophoresis but orders of magnitude faster. (C) 1997 by John Wiley & Sons, Ltd.