Genetics - GEG Tech top picks
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Systematic discovery and perturbation of regulatory genes in human T cells reveals the architecture of immune networks | Nature Genetics

Systematic discovery and perturbation of regulatory genes in human T cells reveals the architecture of immune networks | Nature Genetics | Genetics - GEG Tech top picks | Scoop.it

 

 

 

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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. 

 

 

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Penn biologists show evidence of a two-sided genomic arms race involving repetitive DNA

Penn biologists show evidence of a two-sided genomic arms race involving repetitive DNA | Genetics - GEG Tech top picks | Scoop.it
Biological arms races are commonplace in nature. Cheetahs, for example, have evolved a sleek body form that lends itself to rapid running, enabling them to feast upon similarly speedy gazelles, the fastest of which may evade predation.
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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.   

 

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Researchers discover new genetic driver of autism and other developmental disorders

Researchers discover new genetic driver of autism and other developmental disorders | Genetics - GEG Tech top picks | Scoop.it
A research group including Kobe University's Professor TAKUMI Toru (also a Senior Visiting Scientist at RIKEN Center for Biosystems Dynamics Research) and Assistant Professor TAMADA Kota, both of the Physiology Division in the Graduate School of Medicine, has revealed a causal gene (Necdin, NDN) in autism model mice that have the chromosomal abnormality called copy number variation.
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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.

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Formation of quadruple helix DNA tracked in live human cells for the first time | Imperial News | Imperial College London

Formation of quadruple helix DNA tracked in live human cells for the first time | Imperial News | Imperial College London | Genetics - GEG Tech top picks | Scoop.it
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.
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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.

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Harvard study unlocks a key to regeneration –

Harvard study unlocks a key to regeneration – | Genetics - GEG Tech top picks | Scoop.it

A master regulator of regeneration

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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.

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DNA i-motifs found in human cells

DNA i-motifs found in human cells | Genetics - GEG Tech top picks | Scoop.it
Similar to G-quadruplexes, these folded DNA structures could be selective drug targets
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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.

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Reduced mutation rate in exons due to differential mismatch repair - Nature

Reduced mutation rate in exons due to differential mismatch repair - Nature | Genetics - GEG Tech top picks | Scoop.it
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Here the authors find fewer somatic mutations in exons than expected from their sequence content and demonstrate that this is not due to purifying selection. Instead, they show that it is caused by higher mismatch-repair activity in exonic than in intronic regions. These findings have important implications for understanding of mutational and DNA repair processes and knowledge of the evolution of eukaryotic genes, and they have practical ramifications for the study of evolution of both tumors and species.
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New Technique Searches ‘Dark Genome’ for Disease Mutations - Columbia University Medical Center

New Technique Searches ‘Dark Genome’ for Disease Mutations - Columbia University Medical Center | Genetics - GEG Tech top picks | Scoop.it
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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.

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New insight into how telomeres protect cells from premature senescence

New insight into how telomeres protect cells from premature senescence | Genetics - GEG Tech top picks | Scoop.it
Telomere Length Determines TERRA and R-Loop Regulation through the Cell Cycle
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Researchers found an RNA species identifying critically short telomeres / Publication in Cell

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Psst, the human genome was never completely sequenced

Psst, the human genome was never completely sequenced | Genetics - GEG Tech top picks | Scoop.it
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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.

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Social Networking for the Proteome, Upgraded 

Social Networking for the Proteome, Upgraded  | Genetics - GEG Tech top picks | Scoop.it
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Harvard Medical School researchers have mapped the interaction partners for proteins encoded by more than 5,800 genes, representing over a quarter of the human genome, according to a new study published online in Nature on May 17.

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“Smart” Cephalopods Trade Off Genome Evolution for Prolific RNA Editing

“Smart” Cephalopods Trade Off Genome Evolution for Prolific RNA Editing | Genetics - GEG Tech top picks | Scoop.it
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Octopus, squid, and cuttlefish are famous for engaging in complex behavior, from unlocking an aquarium tank and escaping to instantaneous skin camouflage to hide from predators. A new study suggests their evolutionary path to neural sophistication includes a novel mechanism: Prolific RNA editing at the expense of evolution in their genomic DNA.

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The Origin of Stem Cells

The Origin of Stem Cells | Genetics - GEG Tech top picks | Scoop.it
The protein WOX2 is responsible for enabling plants to develop organs throughout their lives
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Freiburg plant biologist Prof. Dr. Thomas Laux and his research group have published an article in the journal Developmental Cell presenting initial findings on how shoot stem cells in plants form during embryogenesis, the process of embryonic development. Pluripotent stem cells can develop into any type of cell in an organism. In contrast to animals, plants can form completely new organs from their stem cells throughout their lives, which in the case of several species of trees may span a thousand years or more. Stem cell research promises to solve key problems in medicine and plant breeding. However, whereas the function of stem cells for the regeneration of tissue or for growth has been studied in detail, much less is known so far about how stem cells form in the course of embryonic development.

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Synonymous mutations in representative yeast genes are mostly strongly non-neutral - Nature

Synonymous mutations in representative yeast genes are mostly strongly non-neutral - Nature | Genetics - GEG Tech top picks | Scoop.it
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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.

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Researchers identify a gene that plays vital role in the innate human immune system

Researchers identify a gene that plays vital role in the innate human immune system | Genetics - GEG Tech top picks | Scoop.it
Cedars-Sinai investigators have identified a gene that plays an essential role in the innate human 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.
BigField GEG Tech's insight:

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. 

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Specialized protein appears to regulate key step in cancer metastasis

Specialized protein appears to regulate key step in cancer metastasis | Genetics - GEG Tech top picks | Scoop.it
Researchers have identified a specialized protein that appears to help prevent tumor cells from entering the bloodstream and spreading to other parts of the body.
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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.

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Pan-Cancer Analysis of Whole Genomes - Nature

Pan-Cancer Analysis of Whole Genomes - Nature | Genetics - GEG Tech top picks | Scoop.it
Pan-Cancer Analysis of Whole Genomes
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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. 

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Opinion: Consumer DNA Testing Is Crossing into Unethical Territories

Opinion: Consumer DNA Testing Is Crossing into Unethical Territories | Genetics - GEG Tech top picks | Scoop.it
Data don’t support many direct-to-consumer products, from telomere assessments to bespoke diets based on genetic sequences.
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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. 

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Scientists discover a role for 'junk' DNA

Scientists discover a role for 'junk' DNA | Genetics - GEG Tech top picks | Scoop.it

Researchers have determined how satellite DNA, considered to be 'junk DNA,' plays a crucial role in holding the genome together.

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Researchers at the University of Michigan Life Sciences Institute and the Howard Hughes Medical Institute have determined how satellite DNA, considered to be "junk DNA," plays a crucial role in holding the genome together.

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Millions of new genes in human microbiome: Study triples the amount of data on the human microbiome

Millions of new genes in human microbiome: Study triples the amount of data on the human microbiome | Genetics - GEG Tech top picks | Scoop.it
Strains, functions and dynamics in the expanded Human Microbiome Project - Nature
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A new study of the human microbiome has uncovered millions of previously unknown genes from microbial communities in the human gut, skin, mouth, and vaginal microbiome, allowing for new insights into the role these microbes play in human health and disease.

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How are long strands of DNA packed into tiny cells?

How are long strands of DNA packed into tiny cells? | Genetics - GEG Tech top picks | Scoop.it
Structure and Dynamics of a 197 bp Nucleosome in Complex with Linker Histone H1
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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.

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The Piwi‐piRNA pathway: road to immortality

The Piwi‐piRNA pathway: road to immortality | Genetics - GEG Tech top picks | Scoop.it

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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.

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Close-Up View of DNA Replication Yields Surprises

Close-Up View of DNA Replication Yields Surprises | Genetics - GEG Tech top picks | Scoop.it
Independent and Stochastic Action of DNA Polymerases in the Replisome
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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.

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Disentangling chloroplast genetics: Scientists isolate a critical gene for plant health

Disentangling chloroplast genetics: Scientists isolate a critical gene for plant health | Genetics - GEG Tech top picks | Scoop.it

 

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Proper DNA inheritance is essential for healthy chloroplast: the energy center of all plant cells. Researchers discover a new gene in chloroplast that disentangles its DNA for proper plant health.

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Researchers uncover a potent genetic element in Earth’s smallest life forms

Researchers uncover a potent genetic element in Earth’s smallest life forms | Genetics - GEG Tech top picks | Scoop.it
Retroelement-guided protein diversification abounds in vast lineages of Bacteria and Archaea
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It’s the stuff of science fiction, though there’s nothing fiction about it: Researchers have discovered a multitude of previously unidentified microorganisms possess a genetic element that enables them to self-mutate.

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