Whole mitochondrial genome sequencing of Malaysian patients with cardiomyopathy

PeerJ

Sheh Wen Kuan¹  Boon Pin Kee¹  E-Wei Tan¹  Kek Heng Chua¹  Alexander Loch²  Lay Koon Tan³ 

[1]Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

[2]Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

[3]National Heart Institute, Kuala Lumpur, Malaysia

关键词: Cardiomyopathy;    HCM;    DCM;    Whole mitochondrial genome sequencing;    mtDNA;    NGS;   

DOI  :  10.7717/peerj.13265

来源: DOAJ

【 摘 要 】

Cardiomyopathy (CMP) constitutes a diverse group of myocardium diseases affecting the pumping ability of the heart. Genetic predisposition is among the major factors affecting the development of CMP. Globally, there are over 100 genes in autosomal and mitochondrial DNA (mtDNA) that have been reported to be associated with the pathogenesis of CMP. However, most of the genetic studies have been conducted in Western countries, with limited data being available for the Asian population. Therefore, this study aims to investigate the mutation spectrum in the mitochondrial genome of 145 CMP patients in Malaysia. Long-range PCR was employed to amplify the entire mtDNA, and whole mitochondrial genome sequencing was conducted on the MiSeq platform. Raw data was quality checked, mapped, and aligned to the revised Cambridge Reference Sequence (rCRS). Variants were named, annotated, and filtered. The sequencing revealed 1,077 variants, including 18 novel and 17 CMP and/or mitochondrial disease-associated variants after filtering. In-silico predictions suggested that three of the novel variants (m.8573G>C, m.11916T>A and m.11918T>G) in this study are potentially pathogenic. Two confirmed pathogenic variants (m.1555A>G and m.11778G>A) were also found in the CMP patients. The findings of this study shed light on the distribution of mitochondrial mutations in Malaysian CMP patients. Further functional studies are required to elucidate the role of these variants in the development of CMP.

【 授权许可】

Unknown