Heteroplasmic Mitochondrial Genetic Variation in the Human Heart
Heteroplasmic Mitochondrial Genetic Variation in the Human Heart
ABSTRACT Whether heteroplasmic mitochondrial genetic variants in readily accessible tissues (blood, skeletal muscle) reflect those in the human heart (atrial appendage, left ventricle) is unknown. Using next generation sequencing data from paired tissue samples (n=233) collected postmortem in the Genotype-Tissue Expression project, we identified 558 unique heteroplasmic mitochondrial genetic variants across the four tissues, of which only 13% were shared across all four tissue sites. Between the two cardiac sites, 61% of heteroplasmic mitochondrial genetic variants were unique to one site. A greater proportion of the heteroplasmic variants were non-synonymous or frameshift variants in the muscle sites compared to blood or those variants shared across all four tissues. Compared to blood, the total number of heteroplasmic variants was higher in cardiac tissue, which was associated with advancing age. Our findings suggest that human cardiac tissue has unique heteroplasmic mtDNA variants and may be relevant to aging-related diseases.
Moreira Jesse D.、Li Yi、Padera Robert F.、Fetterman Jessica L.、Benjamin Emelia J.、Xue Liying、Gopal Deepa M.、Levy Daniel、Lenburg Marc E.、Liu Chunyu、Smith Karan Kacy、Sun Xianbang
Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of MedicineDepartment of Biostatistics, School of Public Health, Boston UniversityDepartment of Pathology, Brigham and Women?ˉs Hospital, Harvard Medical SchoolEvans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of MedicineEvans Department of Medicine, Section of Cardiovascular Medicine and Department of Epidemiology, Boston University and Boston Medical CenterEvans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of MedicineEvans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of MedicinePopulation Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of HealthEvans Department of Medicine, Section of Computational Biomedicine, Boston University School of MedicineDepartment of Biostatistics, School of Public Health, Boston UniversityEvans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of MedicineDepartment of Biostatistics, School of Public Health, Boston University
基础医学遗传学分子生物学
Moreira Jesse D.,Li Yi,Padera Robert F.,Fetterman Jessica L.,Benjamin Emelia J.,Xue Liying,Gopal Deepa M.,Levy Daniel,Lenburg Marc E.,Liu Chunyu,Smith Karan Kacy,Sun Xianbang.Heteroplasmic Mitochondrial Genetic Variation in the Human Heart[EB/OL].(2025-03-28)[2025-05-26].https://www.biorxiv.org/content/10.1101/2022.07.13.499890.点此复制
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