Use of Next-Generation Sequencing for Identifying Mitochondrial Disorders

Current Issues in Molecular Biology

Gobindo Kumar Paul¹  Shafi Mahmud¹  Md. Abu Saleh¹  Suvro Biswas¹  Md. Robiul Hasan¹  Mst. Sharmin Sultana Shimu¹  Mohasana Akter Mita¹  Shamima Afrose¹  Sanghyun Chung²  Bonglee Kim²  Sultan Alshehri³  Maha Alruwaily⁴  Momammed M. Ghoneim⁴ 

[1] Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi 6205, Bangladesh;Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea;Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia;Department of Pharmacy Practice, College of Pharmacy, AlMaarefa University, Ad Diriyah 13713, Saudi Arabia;

关键词: mitochondrial disorder;    OXPHOS;    mtDNA;    nDNA;    NGS;   

DOI  :  10.3390/cimb44030074

来源: DOAJ

【 摘 要 】

Mitochondria are major contributors to ATP synthesis, generating more than 90% of the total cellular energy production through oxidative phosphorylation (OXPHOS): metabolite oxidation, such as the β-oxidation of fatty acids, and the Krebs’s cycle. OXPHOS inadequacy due to large genetic lesions in mitochondrial as well as nuclear genes and homo- or heteroplasmic point mutations in mitochondrially encoded genes is a characteristic of heterogeneous, maternally inherited genetic disorders known as mitochondrial disorders that affect multisystemic tissues and organs with high energy requirements, resulting in various signs and symptoms. Several traditional diagnostic approaches, including magnetic resonance imaging of the brain, cardiac testing, biochemical screening, variable heteroplasmy genetic testing, identifying clinical features, and skeletal muscle biopsies, are associated with increased risks, high costs, a high degree of false-positive or false-negative results, or a lack of precision, which limits their diagnostic abilities for mitochondrial disorders. Variable heteroplasmy levels, mtDNA depletion, and the identification of pathogenic variants can be detected through genetic sequencing, including the gold standard Sanger sequencing. However, sequencing can be time consuming, and Sanger sequencing can result in the missed recognition of larger structural variations such as CNVs or copy-number variations. Although each sequencing method has its own limitations, genetic sequencing can be an alternative to traditional diagnostic methods. The ever-growing roster of possible mutations has led to the development of next-generation sequencing (NGS). The enhancement of NGS methods can offer a precise diagnosis of the mitochondrial disorder within a short period at a reasonable expense for both research and clinical applications.

【 授权许可】

Unknown