The gene variant APOE4 is finally giving up some of its secrets, spurring new strategies to stop the dreaded neurodegenerative disease

Some bacteria appear to encase their genomes in proteins called histones — which weren’t thought to exist in bacterial cells.

In a recent study published in Science, researchers demonstrated how transketolase-like 1 (TKTL1) gene expression influenced neocortical neurogenesis in modern humans.

In a study published online June 8 in the journal Nature that involved the genetic manipulation of yeast cells in the laboratory, University of Michigan biologists show that most synonymous mutations are strongly harmful.

Cedars-Sinai researchers have identified a gene that plays a key role in the human innate immune system. The gene, NLRP11, helps activate the inflammatory response that tells the body's white blood cells to go on the attack against a foreign presence. The findings, published in Nature Immunology, bring medical science closer to understanding a biological process that can both help and harm the body. The researchers used a gene-editing system called CRISPR/Cas9 to delete genes or introduce genetic mutations into human white blood cells called macrophages. They found that when they deleted NLRP11, it prevented an immune system sensor called the NLRP3 inflammasome from being activated and triggering the inflammatory response. When the researchers restored the NLRP11 gene, the NLRP3 inflammasome sent out its attack signals, triggering the typical inflammatory process. The researchers chose to focus on this particular gene because it is not expressed in mice, leading them to hypothesise that it is an integral part of the complex immune system that exists in humans. 

Researchers have long known that TRPM7 regulates calcium in cells. However, it has recently been shown that TRPM7 appears to help prevent tumor cells from entering the bloodstream and spreading to other parts of the body. TRPM7 senses the pressure of the fluid circulating in the circulation and prevents the cells from spreading through the vascular system. Metastatic tumor cells that can travel and spread have markedly reduced levels of this sensing protein, which is why they effectively enter the circulation instead of turning away from the fluid flow. The researchers further show that artificially increasing TRPM7 expression in tumor cells can help stop intravasation and thus ultimately metastasis: it is at this stage of spread that cancer becomes much more dangerous. When the tumor is said to be "primary", surgery can still save the person. The team therefore hopes that these results could eventually lead to new cancer therapies through the activation of CRISPR, a DNA editing tool.

The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Project performed whole genome sequencing and integrative analysis on over 2,600 primary cancers and their matching normal tissues across 38 distinct tumor types. This study revealed the extensive role played by large-scale structural mutations in cancer, identified previously-unknown cancer-related mutations in gene regulatory regions, inferred tumor evolution across multiple cancer types, illuminated the interactions between somatic mutations and the transcriptome, and studied the role of germline genetic variants in modulating mutational processes. 

Direct-to-consumer DNA testing has provided genetic information to more than 12 million individuals, traditionally for exploring ancestry. While such testing does not violate ethical guidelines, other uses of consumer DNA testing may cross the line. Over the past few years, many of these DNA testing companies have branched out into the realm of precision health, treading into ethically dangerous territories. 

Scientists are a step closer to understanding how DNA, the molecules that carry all of our genetic information, is squeezed into every cell in the body. How DNA is “packaged” in cells influences the activity of our genes and our risk for disease. Elucidating this process will help researchers in all areas of health care, from cancer and heart disease, to muscular dystrophy and osteoarthritis.

Despite its medical, social, and economic significance, understanding what primarily causes aging, that is, the mechanisms of the aging process, remains a fundamental and fascinating problem in biology.  Accumulating evidence indicates that a small RNA-based gene regulatory machinery, the Piwi-piRNA pathway, represents a shared feature of nonaging (potentially immortal) biological systems. Here the authors discuss about the genomic instability induces by transposable elements which could substantially contribute to the aging process.

Almost all life on earth is based on DNA being copied, or replicated, and understanding how this process works could lead to a wide range of discoveries in biology and medicine. Now for the first time scientists have been able to watch individual steps in the replication of a single DNA molecule, with some surprising findings. For one thing, there’s a lot more randomness at work than has been thought.

Prostate cancer tumors harboring BRCA1/2 mutations are exceptionally sensitive to PARP inhibitors, while genomic alterations in other DNA damage response (DDR) genes are less sensitive. To identify previously unknown genes whose loss has a profound impact on PARP inhibitor response, researchers led a multinational effort to perform genome-wide CRISPR-Cas9 knockout screens. The goal of the study was to inform the use of PARP inhibitors beyond BRCA1/2-deficient tumors and to support the re-evaluation of current biomarkers for PARP inhibition in prostate cancer. The study identified several novel genes, for example, MMS22L and RNASEH2B, that are frequently deleted in prostate cancer. These genes could serve as predictive biomarkers for PARP inhibitor response in prostate cancer, the study found. The research team also found that loss of CHEK2 confers resistance, rather than sensitivity, to PARP inhibition. 

US researchers have created the most detailed map to date of how complex networks of genes work together. The new insights into how these genes relate to each other shed light on both the fundamental drivers of immune cell function and immune disease. To carry out this work, the researchers turned to the CRISPR-Cas9 gene editing system, which allowed them to disrupt thousands of genes at once. They focused on genes that make a type of protein called transcription factors. The scientists then studied the impact of disrupting these transcription factors on three immune genes known to play an important role in T cell function: IL2RA, IL-2 and CTLA4. Of the 117 regulators found to control the levels of at least one of the three genes, 39 controlled two of the three, and 10 regulators simultaneously altered the levels of all three genes. Among the full list of genes controlled by the regulators studied, the research team found a high number of genes already linked to immune diseases, including multiple sclerosis, lupus and rheumatoid arthritis. 

Researchers have found evidence of a two-way genomic arms race involving repetitive DNA segments called satellites. Although satellite DNA does not encode genes, it can contribute to essential biological functions, such as the formation of molecular machinery that processes and maintains chromosomes. When satellite repeats are not properly regulated, alterations can occur that are characteristic of cancer and infertility. For their study, the researchers found a fly species, Drosophila simulans, that lacks a satellite repeat that spans 11 million nucleotide base pairs found in its close relative, D. melanogaster. This satellite was known to occupy the same cellular location as a protein called Maternal Haploid (MH). The researchers also had access to a mutant strain of D. melanogaster lacking the 11 million base pair repeats. They then used CRISPR/Cas9 to delete the original MH gene from D. melanogaster. Compared to control females, female flies carrying the D. simulans MH gene had significantly reduced fertility, producing far fewer eggs. Flies that lacked MH completely, however, were unable to produce offspring. In the future, the team will look to see if segments of the genome beyond the satellites are involved and will look in other organisms to further their work.   

A research group including Professor TAKUMI Toru of Kobe University and Assistant Professor TAMADA Kota, both from the Division of Physiology at the Graduate School of Medicine, has shown that the NDN (Necdin) gene, which has a chromosomal abnormality called copy number variation, is responsible for autism in mouse models. The research group identified this gene by performing a synaptic expression-based screen in an animal model of the disorder (15q dup mice). The NDN gene regulates synapse development during the developmental phase and the formation and maturation of dendritic spines during development. Using CRISPR-Cas9, the researchers removed the single copy of the NDN gene from the 15q dup mouse model to generate mice with a normalized genomic copy number for this gene (15q dupΔNdn mouse). Using this model, they demonstrated that the abnormalities observed in 15q dup mice with abnormal spine turnover and decreased inhibitory synaptic input could be ameliorated. Furthermore, they showed that in most behavioral test results of 15q dupΔNdn mice, abnormal behaviors related to sociability and perseveration were improved.

The formation of four-stranded DNA has been tracked in living human cells, allowing scientists to see how it works, and its possible role in cancer.

Led by Assistant Professor of Organismic and Evolutionary Biology Mansi Srivastava, a team of researchers is shedding new light on how animals pull off the feat, along the way uncovering a number of DNA switches that appear to control genes for whole-body regeneration. The study is described in a March 15 paper in Science.

In 2013, a research group confirmed that G-quadruplexes were present in human cells (Nat. Chem.2013, DOI: 10.1038/nchem.1548 and C&EN, Jan. 21, 2013, page 8). Now a separate group, led by Marcel E. Dinger and Daniel Christ of the Garvan Institute of Medical Research, has confirmed that i-motifs are also there (Nat. Chem. 2018, DOI: 10.1038/s41557-018-0046-3). The work helps pave the way for the search for i-motif-targeted drugs.

Researchers have found a way to identify disease-causing genetic mutations in the non-coding region of the genome, which has been uninterpretable until now.

Researchers found an RNA species identifying critically short telomeres / Publication in Cell

Contrary to popular belief, the human genome was never completely sequenced. Some scientists say those gaps may play a role in diseases such as cancer.