Category: Genetics

Categories : Cancer GeneticsTags :

RNA Knockout Halts the Spread of Triple-negative Breast Cancer

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The University of Westminster has released a new study showing that taking out small chunks of human DNA called microRNA can reverse the spread of triple negative breast cancer cells.

The study also suggested that microRNAs could be targeted to spot and treat triple negative breast cancer. Breast cancer is the most common cancer in women, and triple negative breast cancer makes up 10-20% of cases.

MicroRNAs (miRs) have important roles in cellular functioning and signalling, and are heavily involved in the growth and metastasis of cancers. The researchers found that miR-21, a major breast cancer-related RNA, is increased in triple negative breast cancer and is also associated with metastasis.

Using CRISPR/Cas9, the researchers knocked out miR-21 from the cancer cells, and discovered that the cancer cells’ metastatic properties were reversed. They also observed that they released smaller vesicles, which release lipid blobs that play an important part in cancer spread. There was also less miR-21 carried in the vesicles, which also carry disease-related molecules to other cells.

Lead researcher Dr Pinar Uysal-Onganer of the University of Westminster, said: “This is an important study which contributes to better understanding of roles of miRs in aggressive cancer types such as triple negative breast cancer. We are now aiming to clarify the relationships between miR-21 and cancer drug resistance, which is another important factor that limits cancer cure.”

Source: Medical Xpress

Journal information: Elif Damla Arisan et al. MiR-21 is Required for the Epithelial–Mesenchymal Transition in MDA-MB-231 Breast Cancer Cells, International Journal of Molecular Sciences (2021). DOI: 10.3390/ijms22041557

Categories : Cancer GeneticsTags :

New Method to Pick up Mutations Behind Colorectal Cancer Risks

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University of Michigan researchers have developed a method to detect mutations which give rise to colorectal cancer.

Colorectal cancer is the third most common cancer type, and the second most common cause of cancer-related deaths in the United States. Although most cases occur sporadically, some 5 to 10% of cases are hereditary, the most common cause of which is Lynch syndrome. Lynch syndrome results in an 80% increase in the lifetime risk of developing colorectal cancer. Those with a family history of colorectal cancer are advised to start screening before age 45. However, genetic testing for cancer risk does not always provide useful information for those with family history.  

To address this, a new method of genetic testing was developed by Jacob Kitzman, PhD, of the Department of Human Genetics at Michigan Medicine plus together with other colleagues. Since mutations are rare in the human population, determining which one is responsible is difficult, and simply studying one in the lab is too time consuming to be practical.
With deep mutational scanning, the researchers measured the effect of MSH2 mutations, which is one major cause of Lynch syndrome

They deleted the normal copy of MSH2 from human cells with CRISPR-Cas, replacing it with a library of every possible mutation in the MSH2 gene. Each cell in the mix then carried a unique MSH2 mutation. Chemotherapy then killed off only the cells that had a functional variant of MSH2.

The counterintuitive idea, noted Kitzman, is that the surviving cells do not have functioning MSH2—which have mutations that are most likely to cause disease.

“We were basically trying to sit down and make the mutations we could so they could serve as a reference for ones that are newly seen or are amongst the thousands of variants of unknown significance identified in people from clinical testing,” says Kitzman. “Until now, geneticists could not be sure whether these are benign or pathogenic.”

It is hoped that with other patient-specific information, some of these variants could be reclassified, and those individuals advised to undergo more intense screening.

Kitzman said: “One of the next areas that will need some focus in the field of human genetics is to create these sorts of maps for many different genes where there is a clinical connection, so we can be more predictive when variants are found in an individual.”

Source: Medical Xpress

Journal information: Xiaoyan Jia et al, Massively parallel functional testing of MSH2 missense variants conferring Lynch syndrome risk, The American Journal of Human Genetics (2020). DOI: 10.1016/j.ajhg.2020.12.003

Categories : GeneticsTags :

Not Quite Mirror Images: DNA of Identical Twins Differs Slightly

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The popular depiction of identical twins is that they are exactly that – individuals from a single zygote that are identical because their DNA is identical. But new research has shown that there can be a surprisingly large amount of mutations that differentiate one twin from another.

Twin studies have been popular in identifying the genetic basis of traits and conditions, such as vulnerabilities to disease, as well as in psychological studies examining the effects of genetic “nature” versus environmental “nurture”.

Sequencing the DNA of 387 pairs of identical twins, along with their parents, children and spouses, scientists in Iceland were able to find small numbers of early mutations between twins.Identical twins have an average of about 5.2 mutations between them, but in 15%, there were as many as 100 mutations. Such a number of genetic mutations could influence height differences or susceptibility to cancer.

Jan Dumanski, a geneticist at Uppsala University in Sweden, who was not involved in the new paper, said of the results, “The implication is that we have to be very careful when we are using twins as a model” for discerning the influences of nature and nurture.

The study went beyond previous ones that had already discovered small mutations between twins, to include parents, spouses and children, enabling them to pinpoint mutations in two kinds of cell: those present in just one individual and those passed on to their children. In addition, they found mutations occuring before the zygote split into two embryos.

Study co-author Kari Stefansson, a geneticist at the University of Iceland and the company deCODE genetics, said that his team had discovered cases where pairs of twins had mutations that were present in all cells of one twin, but not found in the other twin at all. However, “sometimes the second twin may show the mutation in some cells, but not all cells,” he said.

Source: Medical Express

Journal information: Hakon Jonsson et al. Differences between germline genomes of monozygotic twins, Nature Genetics (2021). DOI: 10.1038/s41588-020-00755-1

Categories : GeneticsTags :

Diet can Affect Sperm through Epigenetics

On By ModernMedia

A team of researchers have investigated the effect of adding nuts to a Western style diet on epigenetic effects of sperm quality.

The epigenetic effects are expressed through DNA methylation, where methyl groups are added to DNA sequences, altering their activity without changing the actual sequence.

A range of lifestyle and environmental factors have been investigated in the search for the cause in the drop of human sperm fertility observed over the pasty 70years. Specific sperm DNA methylation signatures are associated with sperm quality.

The researchers took data from 72 young non-smoking adults from the FERTINUTS trial. In the assigned nut-eating group, the participants’ sperm was found to have significantly sperm count, viability, motility, and morphology. Additionally, alterations in 36 specific DNA methylation regions were observed compared to the control group, and hypermethylation was seen in 97.2% of them.  

Albert Salas-Huetos, first author of the article stated that, “This work demonstrates that there are some sensitive regions of the sperm epigenome that respond to diet, and which can result in changes in sperm and in its ability to fertilise.”

Source: Science Daily

Categories : GeneticsTags :

“Elegant Chemo” Uses CRISPR Tools to Target Tumours

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New research from Tel Aviv University led by Prof Dan Peer, has developed a new system to directly slice DNA in cancer cells, effectively “deleting” them with molecular “scissors”, leaving no side effects, it is claimed. 

“This is the first study in the world to prove that the CRISPR genome editing system, which works by cutting DNA, can effectively be used to treat cancer in an animal,” said Peer.

The treatment increased survival by 30% for mice with gliboglioblastoma, one of the deadliest cancers, and 80% in disseminated ovarian tumours. 

When adapted for humans, the treatment would have to be customised for each individual based on a biopsy and then injected, either into the tumour or generally.

Peer explained that the injection consists of three components: a nanoparticle made from lipids, messenger RNA which “encodes” the “tiny scissor function” for cutting the DNA, and a system which “recognises” cancerous cells.   

Peer said, “When we first spoke of treatments with messenger RNA twelve years ago, people thought it was science fiction. I believe that in the near future, we will see many personalized treatments based on genetic messengers, for cancer and various genetic diseases.”

Source: Times of Israel

Categories : Genetics HIV T-cellsTags :

Long-term HIV Immunisation in Mice with Gene Technology

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While some COVID vaccines are entering the final phases of approval less than a year before the disease was first identified, HIV still has no vaccine after decades of research.

Now, engineered immune cells have elicited a response against HIV in mice, presenting an important first step forward in the quest for a vaccine. These broadly neutralising antibodies (bnabs) are effective against a variety of viruses and neutralise the glycan protecting HIV’s proteins.

Previous research had engineered B cells that produced the same antibodies as seen in rare HIV patients who are able to produce bnabs against HIV after many years. Now, this research has shown that it was possible to mature these into memory and plasma cells, conferring long-lasting protection and even showing improved antibodies can be produced, as in the immunisation process.

Principal investigator James Voss, PhD, of Scripps Research said, “This is the first time it has been shown that modified B cells can create a durable engineered antibody response in a relevant animal model.”

Currently it appears it would be an expensive therapy and a great barrier to many of the 38 million living with HIV around the world. A blood draw would be taken to the lab to engineer a vaccine for the patient, but Voss says that his team is looking to make the procedure inexpensive.

“People think of cell therapies as being very expensive,” Voss said. “We’re doing a lot of work towards trying to make the technology affordable as a preventative HIV vaccine or functional cure that would replace daily antiviral therapy.”

Source: Science Daily

Categories : Ageing GeneticsTags :

Hyperbaric Oxygen Shown to Increase Telomere Length

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In a world first, the length of human telomeres in living subjects has been increased in a prospective clinical trial as part of a broader study of aging. This was accomplished with the use of hyperbaric oxygen therapy (HBOT).

Telomeres place a limit on the number of times cells can be replicated, shortening by 20-40 bases every year and are thought to be one of the causes of aging as shorter telomeres are related to greater vulnerability to disease. Telomere length reduction can be slowed with diet and exercise, but not increased.

The trial recruited 35 participants aged over 63, who did not undergo diet or lifestyle changes. Each patient received 60 HBOT sessions over 90 days. The telomere length of T and B cells significantly increased by over 20%. B cells showed the greatest lengthening at 36.7% post-HBOT.

“After dedicating our HBOT research to exploring its impact on the areas of brain functionality and age related cognitive decline, we have now uncovered for the first time in humans HBOT’s biological effects at the cellular level in healthy aging adults,” said Prof Shai Efrati of the Faculty of Medicine and Sagol School of Neuroscience at Tel Aviv University. “Since telomere shortening is considered the ‘Holy Grail’ of the biology of aging, many pharmacological and environmental interventions are being extensively explored in the hopes of enabling telomere elongation. The significant improvement of telomere length shown during and after these unique HBOT protocols provides the scientific community with a new foundation of understanding that aging can, indeed, be targeted and reversed at the basic cellular-biological level.”

Source: The Sagol Center for Hyperbaric Medicine and Research via PRNewswire

Categories : COVID GeneticsTags :

Spike Protein Mutation May Be COVID’s Achilles Heel

On By ModernMedia

New research suggests that the very spike protein that makes SARS-CoV-2 so infective may also make it more vulnerable to vaccines. The characteristic “crown” of spikes on the virus gives rise to its “coronavirus” name.

A common mutation in the D614G protein makes a flap open in the spike. This spike makes it easier for the virus to latch onto cells, but this same flap opens a pathway directly into the virus’ core. This makes it easier for antibodies, such as those in the vaccines presently undergoing testing, to infiltrate into the virus, and disable it.

Yoshihiro Kawaoka, a virologist at the University of Wisconsin-Madison, explains: “The original spike protein had a ‘D’ at this position, and it was replaced by a ‘G,’ Several papers had already described that this mutation makes the protein more functional and more efficient at getting into cells.”

This mutation, they found, makes the virus replicate 10 times faster and also makes it more infectious.

When hamsters were exposed to the mutated and unmutated coronavirus strains, the ones infected with the mutated strain were found to transmit the virus much faster than those infected with the unmutated strain. Neither strain seemed to make the hamsters sicker, suggesting that the mutation does not make the virus more lethal. Researchers caution that the animal test results may not hold true for humans, and that constant vigilance in observing and documenting mutations in the SARS-CoV-2 virus is necessary. 

Source: Medical Xpress