Fig. 5: Length heteroplasmies at chrM:302 are inherited maternally as mixtures, co-exist in single cells and are under the influence of variation in the nuclear genome.
From: Nuclear genetic control of mtDNA copy number and heteroplasmy in humans
a, Scheme of chrM:302 region with associated G-quadruplex and length heteroplasmy (GmAGn) nomenclature. b, Sibling–sibling transmission of chrM:302 length heteroplasmies. c–e, chrM:302 length heteroplasmy composition across UKB (c), within select UKB mtDNA haplogroups (d) and across 171 single cells in whole blood (e). For c–e, each vertical bar corresponds to a single individual (c,d) or cell (e). For b–e, colours correspond to the legend next to panel d. f, Mean mtCNadj as a function of major chrM:302 allele (red line) and TFAM allele (black dot). Error bars, mean ± 1 s.e.m.; mtCN, copies per diploid nuclear genome; total n = 121,816. g, Case-only mtDNA heteroplasmy GWAS Manhattan plot for chrM:302:A,AC. Red genes are mitochondria-related; *gene with RVAS Cauchy P value at GWS; †CS variants proximal to the gene with PIP > 0.1; ‘c’, missense variant identified in the CS; underline, eQTL colocalization with PIP > 0.1. h, chrM:302 heteroplasmy as a function of highest PIP SNP genotype in SSBP1 locus. Red line, median. i, Quantile–quantile plots of gene-based SKAT-O P values from RVAS for chrM:302:A,AC. Colours represent max MAF of included variants, black line is null expectation, error band is 95% CI under the null. Ref, reference.
