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cell-free DNA (cfDNA) UPSC NOTE

 


cell-free DNA (cfDNA)

  • In the human body, most of the DNA in a genome is neatly packed inside cells with the help of specific proteins, protecting it from being degraded. 

  • However, in a variety of scenarios,some fragments of DNA are ‘released’ from their containers and are present outside the cell, in body fluids. 

  • These small fragments of nucleic acids are widely known as cell-free DNA (cfDNA).

  • cfDNA 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. 

  • Since an array of processes modulates the degradation, the amount, size, and source of the cfDNA can vary across a range as well.

  • In addition, the release of cfDNA 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. 

  • One of the initial reports of the levels of cfDNA in diseases came from studies that were taking a closer look at an autoimmune disease: systemic lupus erythematosus – where the body’s own immune system attacks specific cells.

Applications of cfDNA 

  • cfDNA can be a useful tool to understand human diseases and to use the knowledge to improve diagnosis, monitoring, and prognosis.

Non-invasive prenatal testing:

  • One of the most widely used applications of cfDNA has been in screening foetuses for specific chromosomal abnormalities, an application known as non-invasive prenatal testing. 

  • The availability of affordable genome-sequencing approaches will allow clinicians to sequence cfDNA fragments that correspond to foetal DNA. 

  • They can then use it to understand specific chromosomal abnormalities that involve changes in the chromosomal copy number. 

  • Such changes can lead to conditions 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).

  • As a result, thanks to a cfDNA-based technique, clinicians can now screen mothers from a few millilitres of blood, obtained after nine or ten weeks of pregnancy, to ensure the developing foetus is devoid of such chromosomal abnormalities.

  • 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).

Early detection, diagnosis, and treatment of cancers:

  • Researchers at the Johns Hopkins Kimmel Cancer Centre, Maryland, reported developing a new test they have dubbed ‘Genome-wide Mutational Incidence for Non-Invasive detection of cancer’, or ‘GEMINI’

  • They adopted a whole-genome-sequencing approach to cfDNA extracted from patients.

  • Specifically, the researchers examined a type of genetic mutation that, when combined with machine-learning approaches, could provide a way to detect cancer early. 

  • Using a particular machine-learning model, some genomic data, and data from a computed tomography (CT) scan, the researchers could successfully detect lung cancer – including those with early stage disease – in more than the 90% of the 89 people they studied.

  • They found that combining the new approach with the existing approaches could significantly enhance their ability to detect cancers early.

Understanding why a body is rejecting a transplanted organ:

  • Here, some cfDNA obtained from the donor of the organ – called donor-derived cfDNA, dd-cfDNA – could provide an early yet accurate estimate of how well the organ is being taken up. 

  • Changes in the levels of cfDNA in the blood would precede any biochemical or molecular markers that researchers currently use as a proxy for organ acceptance. 

  • That is, the cfDNA could send a signal earlier than other markers if something is going to go wrong.

Other applications:

  • cfDNA seems to have an almost infinite number of applications, especially as nucleic-acid sequencing becomes rapidly democratised and finds more applications of its own in clinical settings. 

  • 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, and even metabolic disorders such as type-2 diabetes and non-alcoholic fatty liver disease.

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Learnerz IAS | Concept oriented UPSC Classes in Malayalam: cell-free DNA (cfDNA) UPSC NOTE
cell-free DNA (cfDNA) UPSC NOTE
Learnerz IAS | Concept oriented UPSC Classes in Malayalam
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