Thota Kanishka Rao, Amity University Kolkata
Following the resolution of long-standing technical challenges by scientists at the Wellcome Sanger Institute, scientists can now study changes in the DNA of any human tissue for the first time. The new method, known as nanorate sequencing (NanoSeq), allows researchers to study how genetic changes occur in human tissues with unprecedented precision. The study is a significant step forward in cancer and ageing research.
The study, utilising NanoSeq to examine blood, colon, brain, and muscle samples, also calls into question the notion that cell division is the primary mechanism driving genetic changes. The new method is also expected to enable researchers to study the effect of carcinogens on healthy cells more easily and on a much larger scale than was previously possible. Our tissues are made up of both dividing and non-dividing cells. Stem cells regenerate throughout our lives and are in charge of supplying non-dividing cells to keep the body running.
As we age, our cells undergo genetic changes known as somatic mutations. This is a natural process, with cells accumulating between 15 and 40 mutations per year. The majority of these mutations will be harmless, but some will set a cell on the path to cancer. New technologies have also enabled scientists to study mutations in stem cells isolated from healthy tissue in recent years.
However, until now, genome sequencing has not been accurate enough to study new mutations in non-dividing cells, making somatic mutation in the vast majority of our cells impossible to observe precisely. The researchers at Wellcome Sanger Institute sought to improve an advanced sequencing method known as duplex sequencing in this new study. The researchers looked for errors in duplex sequence data and discovered that they were concentrated at the ends of DNA fragments and had other characteristics that suggested flaws in the process of preparing DNA for sequencing. They then improved the DNA preparation process by using specific enzymes to cut DNA more cleanly, as well as improved bioinformatics methods. Over four years, the accuracy was improved to less than five errors per billion letters of DNA.
Researchers have said that it is extremely difficult to detect somatic mutations that are only present in one or a few cells. It is necessary to find a single letter shift across tens of millions of DNA letters, and previous sequencing methods were simply insufficiently accurate. They can now research somatic mutations in any tissue because NanoSeq allows just a few errors per billion DNA letters.
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References:
- Federico Abascal, Luke M. R. Harvey and Emily Mitchell et al. Somatic mutation landscapes at single-molecule resolution. Nature, 2021 DOI: 10.1038/s41586-021-03477-4
- Welcome Trust Sanger Institute. (2021, April 28). Major advance enables study of genetic mutations in any tissue: Research also challenges the idea that cell division is the main mechanism driving genetic changes. ScienceDaily. http://www.sciencedaily.com/releases/2021/04/210428113737.html
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