Four parameters increase the sensitivity and specificity of the exon array analysis and disclose 25 novel aberrantly spliced exons in myotonic dystrophy

Yoshihiro Yamashita, Tohru Matsuura, Jun Shinmi, Yoshinobu Amakusa, Akio Masuda, Mikako Ito, Masanobu Kinoshita, Hirokazu Furuya, Koji Abe, Tohru Ibi, Koo Sahashi, Kinji Ohno

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9 Citations (Scopus)

Abstract

Myotonic dystrophy type 1 (DM1) is an RNA gain-of-function disorder in which abnormally expanded CTG repeats of DMPK sequestrate a splicing trans-factor MBNL1 and upregulate another splicing trans-factor CUGBP1. To identify a diverse array of aberrantly spliced genes, we performed the exon array analysis of DM1 muscles. We analyzed 72 exons by RT-PCR and found that 27 were aberrantly spliced, whereas 45 were not. Among these, 25 were novel and especially splicing aberrations of LDB3 exon 4 and TTN exon 45 were unique to DM1. Retrospective analysis revealed that four parameters efficiently detect aberrantly spliced exons: (i) the signal intensity is high; (ii) the ratio of probe sets with reliable signal intensities (that is, detection above background P-value0.000) is high within a gene; (iii) the splice index (SI) is high; and (iv) SI is deviated from SIs of the other exons that can be estimated by calculating the deviation value (DV). Application of the four parameters gave rise to a sensitivity of 77.8% and a specificity of 95.6% in our data set. We propose that calculation of DV, which is unique to our analysis, is of particular importance in analyzing the exon array data.

Original languageEnglish
Pages (from-to)368-374
Number of pages7
JournalJournal of Human Genetics
Volume57
Issue number6
DOIs
Publication statusPublished - Jun 2012

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Keywords

  • CUGBP1
  • Exon array
  • MBNL1
  • myotonic dystrophy

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Yamashita, Y., Matsuura, T., Shinmi, J., Amakusa, Y., Masuda, A., Ito, M., Kinoshita, M., Furuya, H., Abe, K., Ibi, T., Sahashi, K., & Ohno, K. (2012). Four parameters increase the sensitivity and specificity of the exon array analysis and disclose 25 novel aberrantly spliced exons in myotonic dystrophy. Journal of Human Genetics, 57(6), 368-374. https://doi.org/10.1038/jhg.2012.37