Tag Archives: genes

‘Epigenetic’ Gene Tweaks Could Trigger Cancer

You could be forgiven for thinking of cancer as a genetic disease. Sure, we know it can be triggered by things you do – smoking being the classic example – but most of us probably assume that we get cancer because of a genetic mutation – a glitch in our DNA. It turns out that this is not quite the end of the story.

We now have the first direct evidence that switching off certain genes – something that can be caused by our lifestyle or the environment we live in – can trigger tumours, without mutating the DNA itself. The good news is that these changes are, in theory, reversible.

All cells contain the same DNA, but individual genes in any cell can be switched on or off by the addition or subtraction of a methyl group – a process known as epigenetic methylation.

For years, researchers have known that mutations to our DNA – either those passed on at birth or those acquired as a result of exposure to radiation, for example – can cause cancer. But epigenetic changes have also been implicated in cancer because abnormal patterns of gene methylation are seen in virtually all types of human tumours.

For example, a gene called MLH1 produces a protein that repairs DNA damage. It is often mutated in colon cancer tumours, but in some tumour samples the gene is healthy, but appears to have been silenced by methylationThe problem is that it has been difficult to test whether abnormal methylation occurs as a result of a tumour or is a cause of its growth.

In genetics you can easily delete a gene and see what the consequence is, but it’s much harder to direct methylation to specific regions of the genome,” says Lanlan Shen of Baylor College of Medicine in Houston, Texas.

To get round this problem, Shen and her colleagues used a naturally occurring sequence of DNA, which draws in methyl groups to methylate nearby genes. They call it their “methylation magnet”.

The team inserted this sequence next to the tumour suppressor gene, p16, in mouse embryonic stem cells. These embryos then developed into mice that carry the “methylation magnet” in all of their cells. The team focused on methylating p16 because it is abnormally methylated in numerous cancers.

They monitored the rodents for 18 months – until they reached the mouse equivalent of middle age. Over this time, 30 per cent of the mice developed tumours around their body, including in their liver, colon, lungs and spleen. None of a control group of genetically identical mice developed tumours.

Some tissues showed faster methylation than others, for example in the liver, colon and spleen, and that’s exactly where we saw the tumours grow,” says Shen. “It seems like methylation predisposed the tissue to tumour development.” She reckons that methylation silences p16, which lifts the break that it normally places on any abnormal cell division.

Source: https://www.newscientist.com/

CRISPR-SKIP, New Gene Editing Technique

What if doctors could treat previously incurable genetic diseases caused by errors or mutations in genes? Thanks to new research by American scientists at the University of Illinois, we are one step closer to making that a reality. Published in Genome Biology, their work is based on CRISPR-Cas9, a groundbreaking genome editing system.

Typically, cells in the body “readDNA to produce the proteins needed for different biological functions. . Scientists can change how the DNA is read using CRISPR gene-editing technology. CRISPR-Cas9 is often used to cut out specific areas of DNA and repair faulty genes. In the current study, the researchers modified existing technology to create CRISPR-SKIP. Instead of breaking DNA to cut faulty genes out, CRISPR-SKIP changes a single base of the targeted DNA sequence, causing the cell to skip reading that section of DNA.

According to the study authors, CRISPR-SKIP can eliminate faulty sections of DNA permanently, allowing for long-lasting treatment of some genetic diseases with one treatment. They successfully tested their technique in cell lines from both mice and humans. The scientists aim to test the method in live organisms in the future.

CRISPR-SKIP has the potential to help treat many diseases such as cancer, rheumatoid arthritis, Huntington’s disease, and Duchenne muscular dystrophy to name a few. Because the method only requires editing of a single base, it is simple, precise, and adaptable to a variety of cell types and applications.

Source: https://news.illinois.edu/
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Genes Behind Humankind’s Big Brain

Scientists have pinpointed three genes that may have played a pivotal role in an important milestone in human evolution: the striking increase in brain size that facilitated cognitive advances that helped define what it means to be human. These genes, found only in people, appeared between 3 and 4 million years ago, just prior to a period when the fossil record demonstrates a dramatic brain enlargement in ancestral species in the human lineage, researchers said. The three nearly identical genes, as well as a fourth nonfunctional one, are called NOTCH2NL genes, arising from a gene family dating back hundreds of millions of years and heavily involved in embryonic development. 

The NOTCH2NL genes are particularly active in the reservoir of neural stem cells of the cerebral cortex, the brain’s outer layer responsible for the highest mental functions such as cognition, language, memory, reasoning and consciousness. The genes were found to delay development of cortical stem cells into neurons in the embryo, leading to the production of a higher number of mature nerve cells in this brain region.

The cerebral cortex defines to a large extent what we are as a species and who we are as individuals. Understanding how it emerged in evolution is a fascinating question, touching at the basic origins of mankind,” said developmental neurobiologist Pierre Vanderhaeghen of Université Libre de Bruxelles and VIB/KULeuven in Belgium.

It is the ultimate evolutionary question and it is thrilling to work in this area of research,” added biomolecular engineer David Haussler, scientific director of the University of California, Santa Cruz Genomics Institute and a Howard Hughes Medical Institute investigator.

Source: https://www.reuters.com/