Method of nuclear DNA and mitochondrial DNA analysis

Abstract

An amount of mitochondrial DNA molecules relative to an amount of nuclear DNA molecules is determined in a biological sample, and the relative amount is used for various purposes, e.g., screening, detection, prognostication or monitoring of various physiological and pathological conditions. As examples, an amount of mitochondrial DNA can be used to estimate a concentration of DNA of a tissue type, such as a fetal DNA concentration, tumor DNA concentration, or a concentration of DNA in the biological sample derived from a non-hematopoietic tissue source. Sequencing techniques can be used to determine a mitochondrial DNA concentration in a sample for an accurate detection of a level of cancer. A level of an auto-immune disease is also determined using a relative amount of mitochondrial DNA molecules compared nuclear DNA molecules.

Description

CROSS-REFERENCES TO RELATED APPLICATIONS[0001]This application is a divisional application of U.S. patent application Ser. No. 14 / 993,954, entitled “METHOD OF NUCLEAR DNA AND MITOCHONDRIAL DNA ANALYSIS,” filed on Jan. 12, 2016, which is a non-provisional of and claims priority to U.S. Provisional Patent Application No. 62 / 102,867, entitled “Using Size And Number Aberrations In Plasma DNA For Detecting Cancer,” filed on Jan. 13, 2015; and U.S. Provisional Patent Application No. 62 / 111,524, entitled “Applications Of Plasma Mitochondrial DNA Analysis,” filed on Feb. 3, 2015, each of which is herein incorporated by reference in its entirety for all purposes.BACKGROUND[0002]There is much recent interest in the use of cell-free DNA in plasma and serum for molecular diagnostics. For example, mitochondrial DNA has been detected in the plasma (Chiu et al. Clin Chem 2003; 49: 719-726 and Lo et al. Sci Transl Med 2010; 2: 61-ra91). Measurements have been made of mitochondrial DNA in plasma of ...

AI Technical Summary

Benefits of technology

The patent is for a method to measure fetal DNA in a pregnant woman by measuring the amount of mitochondrial DNA in a sample. This approach is cost-effective and can also be used to measure tumor DNA or a percentage of DNA from non-hematopotic tissue. The relative amount of mitochondrial DNA compared to nuclear DNA can accurately determine the level of cancer or auto-immune disease in an organism. The size distribution of mitochondrial DNA molecules can also provide a statistical value to determine the level of an auto-immune disease.

Problems solved by technology

Measurements have been made of mitochondrial DNA in plasma of cancer patients, but such measurements have not been consistent (Yu M et al.

Further, the uses of a quantification of the mitochondrial DNA have been limited.

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