High Throughput DNA Profiling of Neurological Disorders

Triplet repeat expansions of specific DNA loci have recently been shown to underlie ten neurologicaincluding Huntington's disease, fragile X syndrome, and myotonic dystrophy, and are suspected to bemore. Polymerase chain reaction based analysis of the number of repeats provides diagnostic informatdevelop methodologies for automated, high-throughput DNA analysis for genetic typing of disease markanalysis of undiscovered genes. This proposal describes development of integrated reagents and procetri-, and tetra-nucleotide repeat size typing of fluorescent PCR fragments by capillary array electrPhase I is to optimize multiplex genetic typing protocols for a 96-capillary system and demonstratepolymorphisms with 1,800 samples from families affected with hemochromatosis. The integrated methodssoftware will have the capacity to analyze up to 5.5 million genotypes per year, increasing throughpover current systems. Our goals are to validate the capillary array genetic analysis system for typifragile X syndrome and myotonic dystrophy, and test a proposed genotype-phenotype correlation of mulprogression with repeat polymorphisms in the control region of the myelin basic protein gene.