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Detecting a long insertion variant in SAMD12 by SMRT sequencing: implications of long-read whole-genome sequencing for repeat expansion diseases

Journal of Human Geneticsvolume 64pages191197 (2019) | Download Citation


Long-read sequencing technology is now capable of reading single-molecule DNA with an average read length of more than 10 kb, fully enabling the coverage of large structural variations (SVs). This advantage may pave the way for the detection of unprecedented SVs as well as repeat expansions. Pathogenic SVs of only known genes used to be selectively analyzed based on prior knowledge of target DNA sequence. The unbiased application of long-read whole-genome sequencing (WGS) for the detection of pathogenic SVs has just begun. Here, we apply PacBio SMRT sequencing in a Japanese family with benign adult familial myoclonus epilepsy (BAFME). Our SV selection of low-coverage WGS data (7×) narrowed down the candidates to only six SVs in a 7.16-Mb region of the BAFME1 locus and correctly determined an approximately 4.6-kb SAMD12 intronic repeat insertion, which is causal of BAFME1. These results indicate that long-read WGS is potentially useful for evaluating all of the known SVs in a genome and identifying new disease-causing SVs in combination with other genetic methods to resolve the genetic causes of currently unexplained diseases.

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We would like to thank all of the subjects for participating in this study. We also thank N. Watanabe, T. Miyama, M. Sato, and K. Takabe for their technical assistance and A. Wenger (Pacific Biosciences) for helpful comments. We are also grateful to Edanz Group ( for editing a draft of this manuscript. This work was supported by AMED under grant numbers JP18ek0109280, JP18dm0107090, JP18ek0109301, JP18ek0109348, and JP18kk020500; by JSPS KAKENHI under grant numbers JP17K15630, JP17H01539, JP17K10080, and JP17K15630; by JST under the Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program in the Project for Developing Innovation Systems; the Ministry of Health, Labor, and Welfare; and Takeda Science Foundation.

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  1. Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan

    • Takeshi Mizuguchi
    • , Noriko Miyake
    • , Naomichi Matsumoto
    •  & Satoko Miyatake
  2. Department of Neurology, University of Occupational and Environmental Health School of Medicine, Kitakyushu, 807-8555, Japan

    • Tomoko Toyota
    •  & Hiroaki Adachi
  3. Clinical Genetics Department, Yokohama City University Hospital, Yokohama, 236-0004, Japan

    • Satoko Miyatake


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The authors declare that they have no conflict of interest.

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Correspondence to Takeshi Mizuguchi or Satoko Miyatake.

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