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In silico modeling of pathogenic or possibly pathogenic point mutations in PSEN2

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Abstract

Alzheimer’s disease (AD) is the most common form of neurodegenerative disorder that affects memory, thinking, and behavior. 3 genes found to be involved in early-onset AD encode amyloid precursor protein (APP), presenilin1 (PSEN1), and presenilin2 (PSEN2). Presenilin mutations play a key role, with more than 200 mutations described for PSEN1 and approximately 40 for PSEN2. However, whether mutations cause disease or have effects on protein function is often unknown. For further study, such as genetic counseling and pathogenesis, the important thing we need do is to classify mutations into “pathogenic” or “not pathogenic”. Building a structural context in cell for all mutations is expensive and time consuming. In this study, we summarized substitution mutations in the PSEN2 gene and attempted to identify pathogenic mutations using Polyphen2 (polymorphism phenotyping v2), SIFT (Sorting Intolerant From Tolerant), and 3-D structure analysis techniques.

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Authors and Affiliations

  1. Department of Bionano Technology, Gachon Bionano Research Institute, Gachon University, Seongnam-si, Gyeonggi-do, Republic of Korea

    Yan Cai, Eva Bagyinszky & Seong Soo A. An

  2. Department of Neurology, Seoul National University College of Medicine & Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea

    Sang Yun Kim

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  1. Yan Cai
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  2. Eva Bagyinszky
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  3. Seong Soo A. An
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  4. Sang Yun Kim
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Correspondence to Eva Bagyinszky or Sang Yun Kim.

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Cai, Y., Bagyinszky, E., An, S.S.A. et al. In silico modeling of pathogenic or possibly pathogenic point mutations in PSEN2. Mol. Cell. Toxicol. 12, 453–464 (2016). https://doi.org/10.1007/s13273-016-0050-x

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  • DOI: https://doi.org/10.1007/s13273-016-0050-x

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