Table of Contents > Genomics > Circulating nucleic acids Print

Circulating nucleic acids

Image

Also listed as: Nucleic acids
Background
Methods
Research
Implications
Limitations
Safety
Future research
Author information
Bibliography

Background
  • Genes: Genes are found inside the cells of all organisms. They are located within a specific organelle, or compartment, called the nucleus. An individual's genes are present in a large molecule called DNA (deoxyribonucleic acid), which looks like a twisted ladder. This unique shape is called a double helix. The sides of the double helix are made of alternating sugar and phosphate molecules. The "rungs" of the "ladder" are made of small molecules called bases. There are four different types of these bases in DNA: adenine, thymine, cytosine, and guanine. Because they contain nitrogen, these molecules are sometimes called nitrogen bases.
  • All genes are made up of different combinations of these four molecules, which are arranged in single file in different lengths. The sequence of these molecules provides the "code," or instructions, for making the proteins involved in the development, growth, and function of all the cells in the body.
  • Genes provide instructions for making proteins. In this process, shorter nucleic acid molecules called ribonucleic acid (RNA) are made using segments of DNA as templates. Each RNA molecule is then used as a code to make a protein. Proteins, roughly 30,000 of them, are the primary building blocks of the body and are responsible for the structure and function of cells. In this way, genes are the blueprints that direct the creation of an individual.
  • Circulating nucleic acids: Most of the DNA and RNA in the body is located within cells, but a small amount of DNA can also be found circulating freely in the blood. These DNA and RNA molecules are thought to come from dying cells that release their contents into the blood as they break down. The term "circulating nucleic acids" refers to segments of DNA or RNA found in the bloodstream. Currently, circulating nucleic acids are not used in the clinical setting because large studies have not been performed to determine their usefulness.
  • Molecular genetics: Molecular genetics is the study of genes in the laboratory. Molecular diagnostics is the use of genetic information to diagnose disease, give prognosis for a disease, and guide treatment. Molecular genetic testing can be performed to detect specific genes or specific segments of DNA or RNA. It can also be used to detect circulating nucleic acids in the blood. If an abnormal gene or abnormal segment of a gene is found in the blood, it may reveal a specific disease.
  • Because nucleic acids are released into the blood when the cells die, patients who experience trauma, heart attack, or stroke or those who have cancer may have higher levels of circulating nucleic acids. Some autoimmune disease, such as lupus and rheumatoid arthritis, also produce abnormally high levels of nucleic acids in the blood. The reason this occurs in these diseases is uncertain.

Methods
  • The most common method of detecting nucleic acids in the blood is called polymerase chain reaction, or PCR. This technique uses a small sample of blood and "probe," which is a segment of DNA that attaches to a specific gene or segment of a gene. This piece of DNA or RNA is then multiplied hundreds of times and analyzed. PCR can detect even very small amounts of nucleic acids in the blood. A fluorescent probe may also be used to label a segment of nucleic acid. This makes it possible to visualize the nucleic acid and determine how much of it is present.
  • DNA that is detected in the blood can be sequenced. This means that the exact pattern of nitrogen bases is determined. After sequencing the DNA, researchers can determine if the gene in the patient's blood is different from the gene in normal, healthy cells. A different gene may indicate the presence of a certain disease.
  • DNA microarrays are used to detect many different genes, or gene segments, at one time. In a DNA microarray test, a single sample of blood can be used to detect dozens, hundreds, or thousands of different genes. If abnormal genes are found circulating in the blood, this may mean the patient has a disease.

Research
  • Autoimmune diseases: An autoimmune disease is one in which the patient's immune system attacks his or her own tissue. Examples of autoimmune disease include lupus, rheumatoid arthritis, and some types of thyroid disease. For unknown reasons, autoimmune diseases can cause higher levels of circulating nucleic acids. This may be because overactivity of immune cells causes them to reproduce and die at a higher than normal rate. In the future, it may become possible to use the levels of these nucleic acids to diagnosis and/or assess the severity of autoimmune diseases.
  • Cancer: Much research is focused on the detection of nucleic acids from cancer cells in the blood. Mutations in some genes may cause a cell to multiply out of control. When this happens, cancer may develop. Most, if not all, cancers have mutations in their genes that cause them to multiply abnormally. These mutations may result in the gene being inactive, overactive, or producing an abnormal protein. This is why the cancer cells continue to multiply out of control.
  • As cancer cells multiply, some of them die and release their genetic material into the blood. Detection of specific segments of nucleic acids that are associated with cancer may make it possible to diagnose cancer with a blood test instead of with a biopsy, x-ray, or surgery. Currently, the use of circulating nucleic acids to diagnose cancer is only used in research trials.
  • For example, chronic myelogenous leukemia (CML) is a type of cancer in which white blood cells are produced excessively. CML occurs when an abnormal gene is produced. This gene, called the "Philadelphia chromosome" because it was first discovered in the city of Philadelphia, causes the white blood cells to reproduce constantly. The Philadelphia chromosome can be detected in the blood or the bone marrow of patients with CML, and the presence of this abnormal is gene is required to make the diagnosis.
  • Cell injury: All of the cells in the body rely on a consistent blood supply. Decreased blood supply can cause cell injury. If blood supply is lost for an extended period of time, cells may die. Nucleic acids from injured or dead cells can be detected in the blood. Heart attack, stroke, and physical trauma cause cells injury, which is associated with higher levels of nucleic acids in the blood. Researchers now are trying to identify correlations between the levels of nucleic acids in the blood and the severity of cell injury.
  • Prenatal disease diagnosis: When a woman is pregnant, some of the DNA from the fetus can be found circulating in the mother's blood. These circulating nucleic acids can be analyzed to detect the presence of genetic disorders in the fetus.
  • Viral infection: Viruses in the human body constantly duplicate themselves as older viral particles die off. When viral particles die, the genetic material of the virus can be detected in the bloodstream. Circulating nucleic acids that are derived from viruses are currently being researched as a method of diagnosing and detecting the severity of viral infections. Currently, doctors measure the level of nucleic acids from the hepatitis C virus in patients with this infection to determine the severity of the disease.

Implications
  • Nucleic acids may improve patient care by facilitating early diagnosis and decreasing patient exposure to multiple tests and procedures. Because increased levels of nucleic acids in the blood may precede the appearance of disease symptoms, nucleic acids may aid in early diagnosis. Measurements of nucleic acids in the blood may also decrease the need for other diagnostic procedures such as X-ray, biopsy, and other invasive procedures. Potential uses of these measurements include detecting cancer and diagnosis of disease in the developing fetus.

Limitations
  • Before nucleic acid tests can be useful, researchers must first identify a specific segment of DNA or RNA that is associated with a specific disease. They then have to prove that the presence of the DNA or RNA in the blood correlates with the presence of the disease.

Safety




Future research
  • Future research may focus on using circulating nucleic acids to prevent disease, rather than to diagnose it. In addition, future research will likely focus on the use of circulating nucleic acids to screen for cancer or other diseases before they actually occur. Some researchers have already shown that patients who have been exposed to cancer-causing agents, such as cigarette smoke, have higher levels of circulating nucleic acids long before they develop cancer.

Author information
  • This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography
  1. Chan KCA, Lo YMD. Circulating tumour-derived nucleic acids in cancer patients: potential applications as tumour markers. Br J Cancer. 2007;96:681-685.
  2. Ding C, Chiu RWK, Lau TK, et al. MS analysis of single-nucleotide differences in circulating nucleic acids: Application to noninvasive prenatal diagnosis. Proc Natl Acad Sci USA. 2004; 101:10762-10767.
  3. Gormally E, Hainaut P, Caboux E, et al. Amount of DNA in plasma and cancer risk: a prospective study. Int J Cancer. 2004;111:746-749.
  4. National Human Genome Research Institute. . Accessed May 31, 2008.
  5. Natural Standard: The Authority on Integrative Medicine. . Copyright © 2008. Accessed May 31, 2008.
  6. Swaminathan R, Butt AN. Circulating nucleic acids in plasma and serum: recent developments. Ann N Y Acad Sci. 2006;1075:1-9.
  7. Swarup V, Rajeswari MR. Circulating (cell-free) nucleic acids--a promising, non-invasive tool for early detection of several human diseases. FEBS Letters. 2007;581:795-799.
  8. Taback B, Hoon DS. Circulating nucleic acids in plasma and serum: past, present and future. Curr Opin Mol Ther. 2004 Jun;6(3):273-8.
  9. Taback B, Hoon DS. Circulating nucleic acids and proteomics of plasma/serum: clinical utility. Ann N Y Acad Sci. 2004;1022:1-8.
  10. Tong YK, Lo YM. Diagnostic developments involving cell-free (circulating) nucleic acids. Clin Chim Acta. 2006;363:187-96.
  11. Tsang JC, Lo YM. Circulating nucleic acids in plasma/serum. Pathology. 2007 Apr;39(2):197-207.
  12. Wong BC, Lo YM. Cell-free DNA and RNA in plasma as new tools for molecular diagnostics. Expert Rev Mol Diagn. 2003;3(6):785-97.

Copyright © 2011 Natural Standard (www.naturalstandard.com)


The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

    Top Health
    Conditions
    To learn more, select a condition from the following menu.


    Healthy Living Marketplace
    UAS Labs DDS Probiotics
    Nutribiotic
    Wakunaga of America
    Wakunaga of America
    Natural Vitality
    Carlson Labs