Laser Desorption Mass Spectrometry for Dynamic Mutation Analysis with Clinic Samples

  Dr. C. H. (Winston) Chen and his colleagues in the ORNL Life Sciences Division's Biochemistry and Biophysics Section Photophysics Group, cooperating with Dr. Nicholas Potter at The University of Tennessee Medical Center, recently developed laser desorption mass spectrometry (LDMS) for dynamic mutation analysis with clinic samples, and gave the first demonstration for Huntington Disease (HD) and denatorubral-pallidoluysian atrophy (DRPLA), which are two major genetic neurodege nerative diseases. With LDMS, the number of trinucleotide repeats can be rapidly and reliably measured. The analysis time by LDMS per sample can be a few seconds per sample versus minutes to hours for conventional gel electrophoresis. With LDMS, no radioactive or dye tagging are required. Thus, the cost for analysis can be significantly lower. It has been found that trinucleotide expansion is associated with many other serious genetic diseases. Among those dieases are Spinobulbar muscular atrophy (Kennedy disease), spinocerebellar ataxias, Fragile X, myotonic dystrophy, and FRAZE. LDMS is expected to be able to detect any of the above diseases. Since the analysis time is shorter and the cost can be lower, LDMS has the potential for population screening for these diseases. In addition to the detection of dynamic mutation, the ORNL researchers also cooperated with Dr. Bruce McCord of the FBI Laboratory and Dr. Lan-Yang Chang of the Academia Sinica in Taiwan to apply this technology for DNA fingerprinting for forensic applications. LDMS was successfully used for DNA typing of short tandem repeat (STR) for different loci from several human samples for person identification. These results indicate LDMS can become an important tool for DNA fingerprinting for forensic applications in the future.

Contact: Winston Chen
Phone: (423) 574-5895
E-mail: che@ornl.gov