Faculty, Staff and Student Publications

Language

English

Publication Date

12-7-2023

Journal

International Journal of Molecular Sciences

DOI

10.3390/ijms242417212

PMID

38139039

PMCID

PMC10743237

PubMedCentral® Posted Date

December 2023

PubMedCentral® Full Text Version

Post-Print

Abstract

The human mitochondrial genome (mtDNA) is a circular DNA molecule with a length of 16.6 kb, which contains a total of 37 genes. Somatic mtDNA mutations accumulate with age and environmental exposure, and some types of mtDNA variants may play a role in carcinogenesis. Recent studies observed mtDNA variants not only in kidney tumors but also in adjacent kidney tissues, and mtDNA dysfunction results in kidney injury, including chronic kidney disease (CKD). To investigate whether a relationship exists between heteroplasmic mtDNA variants and kidney function, we performed ultra-deep sequencing (30,000×) based on long-range PCR of DNA from 77 non-tumor kidney tissues of kidney cancer patients with CKD (stages G1 to G5). In total, this analysis detected 697 single-nucleotide variants (SNVs) and 504 indels as heteroplasmic (0.5% ≤ variant allele frequency (VAF) < 95%), and the total number of detected SNVs/indels did not differ between CKD stages. However, the number of deleterious low-level heteroplasmic variants (pathogenic missense, nonsense, frameshift and tRNA) significantly increased with CKD progression (

Keywords

Humans, DNA, Mitochondrial, Heteroplasmy, DNA Copy Number Variations, Carcinoma, Renal Cell, Kidney Neoplasms, Renal Insufficiency, Chronic, Genome, Mitochondrial, mitochondrial genome (mtDNA), mitochondrial copy number (mtDNA-CN), chronic kidney disease (CKD), heteroplasmy

Published Open-Access

yes

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