Detection of mutational frequency and related methods

A method of measuring a mutational frequency of a mitochondrial DNA sequence in a subject, comprising:

• isolating hematopoietic cells from the subject, wherein the hematopoietic cells each contain at least one mitochondrion comprising mitochondrial DNA;
• expanding individual hematopoietic cells into individual clonal populations of hematopoietic cells;
• extracting mitochondrial DNA from each of the clonal populations of hematopoietic cells;
• separately sequencing the same regions of the mitochondrial DNA from each of the clonal populations;
• and
• determining a proportion of the clonal populations of hematopoietic cells exhibiting mitochondrial DNA heterogeneity within the sequenced regions of the mitochondrial DNA, wherein the proportion corresponds to the mutational frequency of the mitochondrial DNA sequence in the subject.

A method of estimating a mutational frequency of a genomic DNA sequence in a subject, comprising:

• isolating hematopoietic cells from a subject, wherein the hematopoietic cells each contain at least one mitochondrion comprising mitochondrial DNA;
• expanding individual hematopoietic cells into individual clonal populations of hematopoietic cells;
• extracting mitochondrial DNA from each of the clonal populations of hematopoietic cells;
• separately sequencing a region of the mitochondrial DNA from each of the clonal populations;
• determining a proportion of the clonal populations of hematopoietic cells exhibiting mitochondrial DNA heterogeneity within the sequenced region;
• and
• correlating the proportion exhibiting mitochondrial DNA heterogeneity to an estimated mutational frequency of genomic DNA from the same subject, thereby estimating the mutational frequency of the genomic DNA sequence in the subject.