Rinsho Shinkeigaku (Clinical Neurology)

The 51st Annual Meeting of the Japanese Society of Neurology

Massively parallel sequence analysis for revealing causes of neuromuscular disorders

Hiroyuki Ishiura, M.D. and Shoji Tsuji, M.D.

Department of Neurology, Graduate School of Medicine, The University of Tokyo

Molecular genetic studies, positional cloning in particular, contributed to progresses in neurology. However, because of a bottleneck of low sequence analysis throughput, large proportions of small families, especially of lateonset hereditary diseases, still remain to be elucidated. The massively parallel sequencers are expected to identify causative genes in such a small but meaningful families and to reveal pathophysiology of the diseases. Multiple system atrophy (MSA) is a neurodegenerative disorder. Pathophysiology of MSA remains largely uncertain despite many studies. Generally, MSA is a sporadic disorder, but there are rare familial aggregations which would provide a strong clue to understand pathophysiology of MSA. With the backgrounds, we analyzed an MSA family with 2 pathologically proven siblings born with consanguineous parents. Linkage study revealed a candidate 70Mb regions in four chromosomes. We carried out wholegenome resequencing of the proband using Illumina GAIIx. Mean depth was 58X, and a total of 3.5 million single nucleotide variations were found. Although the new technologies are highly powerful, to find a mutation from a number of variations, a challenge with bioinformatics should be overcome. Coping with the problem, the high-throughput sequence technologies will further contribute to a breakthrough in neurology.
Full Text of this Article in Japanese PDF (176K)

(CLINICA NEUROL, 50: 957|958, 2010)
key words: Massively parallel sequence, whole genome sequence, multiple system atrophy

(Received: 22-May-10)