Development of DNA microarray-based reseqeuncing system for neurological diseases.

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The purpose of this project is to develop a high throughput mutational analysis system for neurological diseases. The approach consists of 1.to develop microarray bases reseqeuncing of causative genes for neurological diseases. 2.application of comprehensive analysis of candidate genes for sporadic diseases. and 3.analysis of phenotypic variations bases on comprehensive mutational analysis. To accomplish, these aims, we have developed DNA microarrays for Alzheimer's disease, Parkinson disease, amyotrophic lateral sclerosis, adrenoleukodsytrophy, familial spastic paraplegia. We have confirmed that the sensitivity and specificity of DNA microarray-bases reseqeuncing are comparable to those based on dideoxynucleotide chain terminator method. We have applied DMA microarray-based reseqeuncing for comprehensive mutational analysis of causative genes for 43 patients with spastic paraplegia. We have identified 7 patients with SPG4 and a patient with SPG3A. Among the SPG4 patients, there are two sporadic cases, suggesting reduced penetrance of the mutations. Thus, we have demonstrated that the high throughput DNA microarray-based resegeuncing system is highly useful for molecular dissection of neurological diseases including Alzheimer's disease, Parkinson disease, amyotrophic lateral sclerosis, adrenoleukodsytrophy, familial spastic paraplegia