Lifeboat Foundation

Toronto scientists have mapped the genes allowing cancer cells to avoid getting killed by the immune system in a finding that paves the way for the development of immunotherapies that would be effective for larger patient populations and across different tumour types.

“Over the last decade, different forms of immunotherapy have emerged as really potent cancer treatments but the reality is that they only generate durable responses in a fraction of patients and not for all tumour types,” says Jason Moffat, a professor of molecular genetics in the Donnelly Centre for Cellular and Biomolecular Research at the University of Toronto who led the work.

The study also revealed the need for new therapy to take into account the genetic composition of tumours because of mutations in the cancer cells that can potentially make the disease worse in response to treatment, often referred to as cancer resistance mutations.

Who are we? Where did we come from? How did we get here? Throughout the ages, humans have sought answers to these questions, pursuing wisdom through religion, philosophy, and eventually science. Evolutionary analyses published by Genome Biology and Evolution (GBE) allow us to peer into the mirror and better understand ourselves as a species, bringing us closer than ever to uncovering the answers to these long-held questions. GBE’s latest virtual issue on human genetics highlights some of the most exciting research published in the journal within the last year and a half, demonstrating the wide variety of evolutionary approaches to this avenue of research as well as a number of fascinating insights into our own biology.

Taking over a decade to complete, the original Human Genome Project cost nearly $3 billion and involved the collective effort of hundreds of scientists. Since then, advances in sequencing technology have resulted in an explosion in human genetics and genomics research, with an estimated one million human genomes sequenced to date. While this wealth of data has the potential to answer some of our most fundamental questions, unlocking its mysteries has necessitated the invention of new analytic and computational methods and the integration of techniques and ideas from diverse biological sciences, including physiology, anatomy, medicine, population genetics, bioinformatics, and computational, molecular, and evolutionary biology.

A key area of investigation involves identifying ways in which humans differ from other primates—in other words, what makes us human? Several studies published over the last 18 months suggest that part of the answer may be found in transcriptional regulation and changes in gene expression. Edsall et al. (2019) evaluated differences in chromatin accessibility, which impacts access of the transcriptional machinery to the DNA, across five primates including humans. They found high levels of differentiation across species, as well as classes of sites that differed based on selection, genomic location, and cell type specificity. More specifically, Swain-Lenz et al. (2019) found that differences in chromatin accessibility near genes involved in lipid metabolism may provide a mechanistic explanation for the higher levels of body fat observed in humans compared to other primates. Arakawa et al.

The removal of one gene renders poxviruses—a lethal family of viral infections that are known to spread from animals to humans—harmless, a new study in the journal Science Advances reports.

During this ground-breaking study, scientists from the Spanish National Research Council and the University of Surrey investigated the immune response of cells to poxviruses. Poxviruses, such as cowpox and monkeypox, can spread to humans from infected animals, causing skin lesions, fever, swollen lymph nodes and even death.

Viruses contain genetic material which helps them outsmart host cells, enabling replication and the spread of the infection. Cells in the body are comprised of molecules that sense the presence of viruses, sometimes via the recognition of their genetic material, and alert the immune system of an upcoming infection. Poxviruses, unlike other viruses, are highly unusual in that they have large DNA genomes that are replicated exclusively in the cell cytosol, an area of the cell full of sensors. How poxviruses manage to stay undetectable has remained unknown.

In the past decade, researchers have engineered an array of new tools that control the balance of genetic inheritance. Based on CRISPR technology, such gene drives are poised to move from the laboratory into the wild where they are being engineered to suppress devastating diseases such as mosquito-borne malaria, dengue, Zika, chikungunya, yellow fever and West Nile. Gene drives carry the power to immunize mosquitoes against malarial parasites, or act as genetic insecticides that reduce mosquito populations.

Although the newest gene drives have been proven to spread efficiently as designed in laboratory settings, concerns have been raised regarding the safety of releasing such systems into wild populations. Questions have emerged about the predictability and controllability of gene drives and whether, once let loose, they can be recalled in the field if they spread beyond their intended application region.

Now, scientists at the University of California San Diego and their colleagues have developed two new active genetic systems that address such risks by halting or eliminating gene drives in the wild. On Sept.18, 2020 in the journal Molecular Cell, research led by Xiang-Ru Xu, Emily Bulger and Valentino Gantz in the Division of Biological Sciences offers two new solutions based on elements developed in the common fruit fly.

By studying the DNA of people who lived in East Asia thousands of years ago, scientists are starting to untangle how the region was populated.

Myotonic dystrophy type I is the most common type of adult-onset muscular dystrophy. People with the condition inherit repeated DNA segments that lead to the toxic buildup of repetitive RNA, the messenger that carries a gene’s recipe to the cell’s protein-making machinery. As a result, people born with myotonic dystrophy experience progressive muscle wasting and weakness and a wide variety of other debilitating symptoms.

CRISPR-Cas9 is a technique increasingly used in efforts to correct the genetic (DNA) defects that cause a variety of diseases. A few years ago, University of California San Diego School of Medicine researchers redirected the technique to instead modify RNA in a method they call RNA-targeting Cas9 (RCas9).

In a new study, publishing September 14, 2020 in Nature Biomedical Engineering, the team demonstrates that one dose of RCas9 gene therapy can chew up toxic RNA and almost completely reverse symptoms in a mouse model of myotonic dystrophy.

A forthcoming study from 23andMe shows that a person’s genetic code could affect how severely they experience Covid-19.

From the data, the GTEx team could identify the relationship between specific genes and a type of regulatory DNA called expression quantitative trait loci, or eQTL. At least one eQTL regulates almost every human gene, and each eQTL can regulate more than one gene, influencing expression, GTEx member and human geneticist Kristin Ardlie of the Broad Institute tells Science.

Another major takeaway from the analyses was that sex affected gene expression in almost all of the tissue types, from heart to lung to brain cells. “The vast majority of biology is shared by males and females,” yet the gene expression differences are vast and might explain differences in disease progression, GTEx study coauthor Barbara Stranger of Northwestern University’s Feinberg School of Medicine tells Science. “In the future, this knowledge may contribute to personalized medicine, where we consider biological sex as one of the relevant components of an individual’s characteristics,” she says in a statement issued by the Centre for Genome Regulation in Barcelona, where some of the researchers who participated in the GTEx project work.

Another of the studies bolsters the association between telomere length, ancestry, and aging. Telomere length is typically measured in blood cells; GTEx researchers examined it in 23 different tissue types and found blood is indeed a good proxy for overall length in other tissues. The team also showed that, as previously reported, shorter telomeres were associated with aging and longer ones were found in people of African ancestry. But not all earlier results held; the authors didn’t see a pattern of longer telomeres in females or constantly shorter telomeres across the tissues of smokers as previous studies had.

Continue reading “New Map Charts Genetic Expression Across Tissue Types, Sexes” »

Because much cancer research and clinical trials have been based on white populations, efforts to explore the ways race and ethnicity influence disease are underway.