Cell-free DNA and its applications

Subject : Science and technology

Section: Biotechnology

What is Cell-free DNA (cfDNA)?

Cell-free DNA (cfDNA) are fragment of DNA released from cells into the circulatory system throughout the body, outside their neatly packed cells.

A useful tool

These can be generated and released from a cell in a number of possible situations, including when a cell is dying and the nucleic acids become degraded.
As Biomarker: The release could occur together with a variety of processes, including those required for normal development, those related to the development of certain cancers, and those associated with several other diseases.
For example – detection of an autoimmune disease using cfDNA: systemic lupus erythematosus – where the body’s own immune system attacks specific cells.

Checking the baby

Screening foetuses for specific chromosomal abnormalities, an application known as non-invasive prenatal testing (clinicians can now screen mothers from a few millilitres of blood, obtained after nine or ten weeks of pregnancy).
Genome sequencing approaches allows clinicians to sequence cfDNA fragments that correspond to foetal DNA and to understand specific chromosomal abnormalities.
- Such as Down’s syndrome, which is due to a change in chromosome 21 (there are three copies of chromosome 21 in place of two, so it is also called trisomy 21).
- The test is almost 99% accurate for trisomy 21 or Down’s syndrome and a bit less so for other common trisomies (of chromosomes 13 and 18).
Invasive prenatal testing: Before the genome sequencing the process entailed inserting a fine needle into the body to retrieve the amniotic fluid and cells covering the developing foetus, and analysing them in the lab. This method carries risks to both the foetus and the mother.
Limitations: a positive test result on a cfDNA test should always be followed up with a confirmation test.

Catching a cancer

Emerging application of cfDNA is in the early detection, diagnosis, and treatment of cancers.
GEMINI test: Genome wide Mutational Incidence for Non-Invasive detection of cancer using whole-genome-sequencing approach to cfDNA
The researchers examined a type of genetic mutation that, when combined with machine-learning approaches, combined with some genomic data, and data from a computed tomography (CT) scan could enhance a way to detect cancer early (combination of new approaches with existing)

Almost infinite applications

Understanding why a body is rejecting a transplanted organ:
- Here, some cfDNA obtained from the donor of the organ – called donor derived cfDNA, ddcfDNA – could provide an early yet accurate estimate of how well the organ is being taken up.
- The cfDNA could send a signal earlier than other biomarkers if something is going to go wrong.
There have already been some reports suggesting that cfDNA could be used as a biomarker for neurological disorders like –
- Alzheimer’s disease,
- neuronal tumours,
- stroke,
- traumatic brain injury,
- metabolic disorders such as type2 diabetes and non-alcoholic fatty liver disease.