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03 August 2023 – The Hindu

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Cell-free DNA

Introduction:

  • Some DNA fragments, however, are “released” from their containers under a variety of conditions and are discovered in physiological fluids that are present outside the cell. These little nucleic acid fragments are commonly referred to as “cell-free DNA” (cfDNA).

A valuable tool:

  • For instance, cfDNA can be created and released from a dying cell when the nucleic acids begin to degrade and the cell is in the process of dying.
  • The source, amount, and size of the cfDNA can all change since a number of variables control how it degrades.
  • Events like those required for normal development, those implicated in the genesis of particular cancers, and those connected to a variety of other illnesses may all be associated with the release of cfDNA.
  • One of the first studies on cfDNA levels in diseases focused on systemic lupus erythematosus, an autoimmune disease in which certain cells are attacked by the body’s immune system.

Looking at the baby:

  • One of the most widely used uses of cfDNA is non-invasive prenatal diagnostics, which entails checking foetuses for certain chromosomal diseases.
  • Now that accessible genome-sequencing techniques are available, clinicians will be able to sequence cfDNA fragments that are associated with foetal DNA.
  • They could use it afterwards to understand specific chromosomal disorders involving changes to the chromosomal copy number.
  • Such modifications can lead to diseases like Down’s syndrome, which is caused by a mutation in chromosome 21.
  • Doctors may now check mothers using a few millilitres of blood, obtained after nine or ten weeks of pregnancy, using a cfDNA-based method to make sure the developing infant is free of such chromosomal disorders.
  • The test is roughly 99% accurate for trisomy 21, or Down’s syndrome, but less so for other prevalent trisomies (of chromosomes 13 and 18).
  • It would have taken a tiny incision to retrieve the amniotic fluid and cells around the developing infant, then lab analysis to find these problems before the genome-sequencing era. Using this method puts both the mother and the foetus at danger.

Acquiring cancer:

  • A recent application of cfDNA is the early detection, diagnosis, and treatment of cancers.
  • Researchers unveiled a brand-new test called “Genome-wide Mutational Incidence for Non-Invasive detection of cancer,” or “GEMINI,” last month. They examined the patient’s cfDNA using whole-genome sequencing.
  • The study concentrated on one specific genetic anomaly that, in combination with machine learning methods, may provide a mechanism to detect cancer early.
  • Using a particular machine-learning model, particular genomic data, and details from a computed tomography (CT) scan, the researchers were able to recognise lung cancer.
  • More than 300 persons who had a very high risk of developing lung cancer could also be identified, it was found.

Practically limitless applications:

  • The application of cfDNA is growing, and one such application is in determining why a body rejects a donated organ.
  • Donor-derived cfDNA, also known as dd-cfDNA, can be used in this situation to get a quick but accurate idea of how well the organ is assimilating.
  • In fact, cfDNA looks to have an almost infinite number of applications, especially as nucleic-acid sequencing becomes rapidly more widely available to the public and expands its own applications in therapeutic settings.
  • Some sources claim that cfDNA has the potential to become a biomarker in the future for a variety of diseases, including type 2 diabetes, non-alcoholic fatty liver disease, and neurological illnesses like Alzheimer’s disease, neuronal tumours, stroke, and traumatic brain injury.

Conclusion:

  • By enabling more precise illness screening and early detection, cfDNA sequencing actually offers to put us on the path to a healthy planet.

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