June 8, 2023


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Scientists looking at the human genome have a new “game”. Accuracy up to 100 times higher!

Research by MIT scientists was published in normal genetics, indicating that many genes interact with dozens of different regulators. Identification of the regulatory elements that influence genes can help unravel the mysteries of the development of specific diseases, as well as develop approaches to treat them.

The genome is 100 times more accurate than before

Much of the human genome consists of so-called regulatory regions that decide and control which genes are expressed at what times in the cell. Such an internal organization is necessary to maintain a state of balance, just as if there were road accidents without traffic lights.

Regulatory elements such as enhancers, which are short DNA sequences that can help activate gene transcription, can be located close to a target gene or within 2 million base pairs. To enable these interactions, the genome transforms into a three-dimensional structure that holds distal regions together. New technology allows these interactions to be seen in high resolution.

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The Hi-C technique used so far has revealed that the genome is organized into a structure that allows cells to tightly package their DNA, thus unwinding and folding it as needed. Hi-C has limited resolution, so it is difficult to distinguish interactions between genes and their regulators.

This is where new technology comes in, called Micro-C, which allows you to see genetic interactions at a higher resolution. This is due to an enzyme known as a microcosm exonuclease, which allows genome defragmentation. Hi-C restriction enzymes cut the genome into specific, randomly distributed DNA sequences, resulting in fragments of different and larger sizes. In contrast, microalgal exonucleases uniformly cut the genome into nucleosome-sized fragments, each of 150–200 base pairs of DNA. This in turn enables higher accuracy.

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a. Anders Sejr Hansen of MIT says:

Now we have a way to obtain super-resolution 3D genome structure maps in an affordable way.

Micro-C mapping the entire human genome would cost more than $1 billion, so the researchers developed a method for more targeted sequencing of genome interactions, allowing them to focus on the parts of the genome that contain genes of interest. A method called Region Capture Micro-C can create maps that are 100 times richer in information than other technologies and at a fraction of the cost.