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Clinical genetic strategies for early onset neurodegenerative diseases

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Abstract

Purpose of review

Methods for the genetic diagnosis of neurodegenerative disorders were reviewed, including their backgrounds and applications in the laboratory. Majority of disease-causing gene mutations were uncommon in the general population, where dominant variations could be easily identified in certain disorders. The development of molecular, next generation sequencing (NGS) and cytogenetic techniques allowed to identify multiple genetic mutations leading to diseases. Using of the accurate multivariate diagnosis of diseases would be essential for appropriate treatment of patients, genetic counseling and prevention strategies

Recent findings

Abnormal genes play an extremely important role in the pathogenesis of neurodegenerative disorders of the nervous system. Many studies of genetic have clearly indicated that the molecular mechanisms underlying the etiology and pathogenesis of most neurodegenerative disorders until now. Mutation is necessary for life, while fidelity is necessary for DNA replication. Mistakes in DNA replication/transcription can cause cells to produce either too much or too little protein or a defective protein. Studies on mutations have revealed the normal functions of genes, messages, proteins, the causes of many diseases, and the variability of responses among individuals. Based on the presence of damaging variants, there are many genes have identified that associated with neurodegenerative disorders through to genetic analyses of patients. This declaration is interesting because also our previous analysis has shown that several types of neurodegenerative diseases associated with abnormal genes function have been well described, including Alzheimer’s disease (AD), front temporal dementia (FTD), amyotrophic lateral sclerosis (ALS), prion disease, and Parkinson’s disease (PD). Since the potential treatment strategies for these disorders may be more successful during the pre-clinical stages than in the actual clinical setup, accurate, simple, and affordable diagnostic methods are needed. A mutation can be defined as a sequence change in a test sample compared to the sequence of a reference standard. This has led to the development of methods for screening and detecting abnormal DNA, including techniques that detect previously described mutations (genotyping) and those that scan for mutations in a particular target region (mutation scanning). This review provides a broad overview of the range of currently available mutation detection techniques with special emphasis on neurodegenerative disorders in humans. We have discussed the methods used for detecting unknown mutations, such as ribonuclease, denaturing gradient-gel electrophoresis, carbodiimide, chemical cleavage, single- strand conformation polymorphism, heteroduplex, and sequencing. Furthermore, other diagnostic methods for testing mutations include allele-specific oligonucleotide hybridization; allele-specific amplification, ligation, primer extension, and the artificial introduction of restriction sites are also reviewed. In order to identify the mutation, the last of the work provides basic insights into some of the most popular in silico tools for splicing defect prediction from the viewpoint of end users.

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Authors and Affiliations

  1. Department of BionanoTechnology, Gachon Medical Research Institute, Gachon University, Sungnam, Republic of Korea

    Vo Van Giau, Eva Bagyinszky & Seong Soo A. An

  2. Department of Neurology, Seoul National University College of Medicine & Neurocognitive Behavior Center, Seoul National University Bundang Hospital, Seoul, Republic of Korea

    SangYun Kim

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  1. Vo Van Giau
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  2. Eva Bagyinszky
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  3. Seong Soo A. An
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  4. SangYun Kim
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Correspondence to Eva Bagyinszky or Seong Soo A. An.

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Giau, V.V., Bagyinszky, E., An, S.S.A. et al. Clinical genetic strategies for early onset neurodegenerative diseases. Mol. Cell. Toxicol. 14, 123–142 (2018). https://doi.org/10.1007/s13273-018-0015-3

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  • DOI: https://doi.org/10.1007/s13273-018-0015-3

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