Category Archives: Genome

How do I identify codon numbers with the UCSC Genome Browser?
This tutorial will demonstrate how to locate amino acid numbers for coding genes using the UCSC Genome Browser. 0:36 - Set up the Genome Browser display. 1:35 - Open genes tracks: UCSC Genes, ...

By: UCSC Genome Browser

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How do I identify codon numbers with the UCSC Genome Browser? - Video

The gene editing method called CRISPR is already used in the lab to insert and remove genome defects in animal embryos

Genome editing has generated controversy, with unconfirmed reports of its use in human embryos. Credit: NIAID/Flickr

A tweak to a technique that edits DNA with pinpoint precision has boosted its ability to correct defective genes in people. Called CRISPR, the method is already used in the lab to insert and remove genome defects in animal embryos. But the genetic instructions for the machinery on which CRISPR reliesa gene-editing enzyme called Cas9 and RNA molecules that guide it to its targetare simply too large to be efficiently ferried into most of the human bodys cells.

This week, researchers report a possible way around that obstacle: a Cas9 enzyme that is encoded by a gene about three-quarters the size of the one currently used. The finding, published on 1April inNature, could open the door to new treatments for a host of genetic maladies (F. A. Ranetal. Naturehttp://dx.doi.org/10.1038/nature14299; 2015).

There are thousands of diseases in humans associated with specific genetic changes, says David Liu, a chemical biologist at Harvard University in Cambridge, Massachusetts, who was not involved in the latest study. A fairly large fraction of those have the potential to be addressed using genome editing.

Genome editing has generated controversy, with unconfirmed reports of its use in human embryos. Some scientists have expressed concern that the technique might be used by fertility doctors to edit the genes of human embryos before its safety is established (see alsoE.Lanphieret al. Nature519,410411; 2015). That concern is exacerbated by the fact that changes made by the procedure in embryos would be passed to all subsequent generations without giving anyone affected the opportunity to consent (seeNature519,272; 2015). But in the non-reproductive cells of children and adults, where intergenerational issues are not a concern, researchers and companies are already racing to develop CRISPR as a clinical tool.

The ethics of that pursuit may be more straightforward, but its execution can be harder than using CRISPR in embryos. An embryo consists of a small number of cells that give rise to a human. To edit the genome at that stage is simply a matter of injecting the necessary CRISPR components into a few cells. An adult human, however, is a mix of trillions of cells assembled into many different tissues. Researchers fret over how to target the CRISPR machinery to the specific cells where defective genes are disrupting physiological processes.

You can have the most optimal gene-editing system in the world, but if you cant deliver it to the proper cell type, its irrelevant, says Nessan Bermingham, chief executive of Intellia Therapeutics in Cambridge, Massachusetts, which aims to bring genome editing to the clinic. Were spending a tremendous amount of time working on it.

Snug fit Gene-therapy researchers often harness a virus called AAV to shuttle foreign genes into mature human cells. However, most laboratories use a gene encoding the Cas9 protein that is too large to fit in the snug confines of the AAV genome alongside the extra sequences necessary for Cas9 function.

Feng Zhang of the Broad Institute of MIT and Harvard in Cambridge, Massachusetts, and his colleagues decided to raid bacterial genomes for a solution, because the CRISPR system is derived from a process that bacteria use to snip unwanted DNA sequences out of their genomes. Zhangs team analysed genes encoding more than 600 Cas9 enzymes from hundreds of bacteria in search of a smaller version that could be packaged in AAV and delivered to mature cells.

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New Discovery Moves Gene Editing Closer to Use in Humans

Scientists in the BIDMC Cancer Research Institute discover that the non-coding BRAF pseudogene leads to the development of an aggressive lymphoma-like cancer in animal models

BOSTON -- Pseudogenes, a sub-class of long non-coding RNA (lncRNA) that developed from the genome's 20,000 protein-coding genes but lost the ability to produce proteins, have long been considered nothing more than genomic "junk." Yet the retention of these 20,000 mysterious remnants during evolution has suggested that they may in fact possess biological functions and contribute to the development of disease.

Now, a team led by investigators in the Cancer Research Institute at Beth Israel Deaconess Medical Center (BIDMC) has provided some of the first evidence that one of these non-coding "evolutionary relics" actually has a role in causing cancer.

In a new study in the journal Cell, publishing online today, the scientists report that independent of any other mutations, abnormal amounts of the BRAF pseudogene led to the development of an aggressive lymphoma-like disease in a mouse model, a discovery that suggests that pseudogenes may play a primary role in a variety of diseases. Importantly, the new discovery also suggests that with the addition of this vast "dark matter" the functional genome could be tremendously larger than previously thought - triple or quadruple its current known size.

"Our mouse model of the BRAF pseudogene developed cancer as rapidly and aggressively as it would if you were to express the protein-coding BRAF oncogene," explains senior author Pier Paolo Pandolfi, MD, PhD, Director of the Cancer Center and co-founder of the Institute for RNA Medicine (iRM) at BIDMC and George C. Reisman Professor of Medicine at Harvard Medical School. "It's remarkable that this very aggressive phenotype, resembling human diffuse large B-cell lymphoma, was driven by a piece of so-called 'junk RNA.' As attention turns to precision medicine and the tremendous promise of targeted cancer therapies, all of this vast non-coding material needs to be taken into account. In the past, we have found non-coding RNA to be overexpressed, or misexpressed, but because no one knew what to do with this information it was swept under the carpet. Now we can see that it plays a vital role. We have to study this material, we have to sequence it and we have to take advantage of the tremendous opportunity that it offers for cancer therapy."

The new discovery hinges on the concept of competing endogenous RNAs (ceRNA), a functional capability for pseudogenes first described by Pandolfi almost five years ago when his laboratory discovered that pseudogenes and other noncoding RNAs could act as "decoys" to divert and sequester tiny pieces of RNA known as microRNAs away from their protein-coding counterparts to regulate gene expression.

"Our discovery of these 'decoys' revealed a novel new role for messenger RNA, demonstrating that beyond serving as a genetic intermediary in the protein-making process, messenger RNAs could actually regulate expression of one another through this sophisticated new ceRNA 'language,'" says Pandolfi. The team demonstrated in cell culture experiments that when microRNAs were hindered in fulfilling their regulatory function by these microRNA decoys there could be severe consequences, including making cancer cells more aggressive.

In this new paper, the authors wanted to determine if this same ceRNA "cross talk" took place in a living organism -- and if it would result in similar consequences.

"We conducted a proof-of-principle experiment using the BRAF pseudogene," explains first author Florian Karreth, PhD, who conducted this work as a postdoctoral fellow in the Pandolfi laboratory. "We investigated whether this pseudogene exerts critical functions in the context of a whole organism and whether its disruption contributes to the development of disease." The investigators focused on the BRAF pseudogene because of its potential ability to regulate the levels of the BRAF protein, a well-known proto-oncogene linked to numerous types of cancer. In addition, says Karreth, the BRAF pseudogene is known to exist in both humans and mice.

The investigators began by testing the BRAF pseudogene in tissue culture. Their findings demonstrated that when overexpressed, the pseudogene did indeed operate as a microRNA decoy that increased the amounts of the BRAF protein. This, in turn, stimulated the MAP-kinase signaling cascade, a pathway through which the BRAF protein controls cell proliferation, differentiation and survival and which is commonly found to be hyperactive in cancer.

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An 'evolutionary relic' of the genome causes cancer

SGD Help: Reference Sequence
The annotation of the Saccharomyces cerevisiae strain S288C Reference Genome Sequence in SGD is described in different ways on different pages. Access to GenBank and RefSeq files for the 16...

By: Saccharomyces Genome Database

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SGD Help: Reference Sequence - Video

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Newswise Many microbes cannot be cultivated in a laboratory setting, hindering attempts to understand Earths microbial diversity. Since microbes are heavily involved in, and critically important to environmental processes from nutrient recycling, to carbon processing, to the fertility of topsoils, to the health and growth of plants and forests, accurately characterizing them, as a basis for understanding their activities, is a major goal of the Department of Energy (DOE). One approach has been to study collected DNA extracted from the complex microbial community, or the metagenome, in order to describe its DNA-coded parts catalog and understand how microbes respond and adapt to environmental changes. Studying a population rather than an individual raises different obstacles on the path to knowledge. The challenges of assembling genes and genomic fragments into meaningful sequence information for an unknown microbe has been likened to putting together a jigsaw puzzle without knowing what the final picture should look like, or even if you have all the pieces.

For metagenomics, said Jillian Banfield of the University of California, Berkeley and Lawrence Berkeley National Laboratorys Earth Sciences Division, a longtime collaborator of the DOE Joint Genome Institute (DOE JGI), a DOE Office of Science User Facility, it is like reconstructing puzzles from a mixture of pieces from many different puzzlesand not knowing what any of them look like. Part of the problem lies in the fact that the more commonly used sequencing machines generate data in short lengths or fragments, on the order of a few hundred base pairs of DNA. Additionally, short-read assemblers may not be able to distinguish among multiple occurrences of the same or similar sequences and will therefore either fail to place them in the correct context, or eliminate them entirely from the final assembly, in the same way that putting together a jigsaw puzzle with many small pieces that look the same, is difficult. The result of this are gaps that indicate not all of the microbes in a community can be identified through the application of environmental genomics.

In a study published on the cover of the April 2015 edition of Genome Research, a team including DOE JGI and Berkeley Lab researchers compared two ways of using the next generation Illumina sequencing machines, one of which--TruSeq Synthetic Long-Reads--produced significantly longer reads than the other. Metagenome data were generated from the Berkeley Lab-led DOE subsurface biogeochemistry field study site in Rifle, Colorado by a Banfield-led team. They evaluated the accuracy of the genomes reconstructed from the sequences produced by the two Illumina technologies to learn more about the microbes present in lower amounts than others and better determine the species richness of the metagenome samples.

The project is part of the Berkeley Lab Genomes-to-Watershed Scientific Focus Area (SFA), which involves over 50 scientists from Berkeley Lab and other institutions including UC Berkeley, Pacific Northwest National Laboratory, Colorado School of Mines, and Oak Ridge National Laboratory. The Genomes-to-Watershed SFA is led by geophysicist Susan Hubbard, the director of Berkeley Labs Earth Sciences Division. Its goal is to develop an approach for gaining a predictive understanding of complex, biologically based system interactions from the genome to the watershed scale. Jill Banfield is a co-lead of the Metabolic Potential component of this team project, which focuses on characterizing prevalent metabolic pathways in subsurface microbial communities that mediate carbon and electron flux, and using that information to inform genome-enabled watershed reactive transport simulators. Banfield describes the Metabolic Potential component of the SFA effort in this video, and some of her groups other recent groundbreaking subsurface ecogenomic findings associated with this project can be found here.

Revisiting Microbial Communities in Rifle, Colorado

For the study, the team used sediment samples collected from an aquifer adjacent to the Colorado River, which had been used for previous experiments. For one of these earlier efforts the DOE JGI sequenced Rifle Site microbial communities and was able to completely reconstruct a high quality genome of a previously unknown organism from short-read assemblies. Additionally, the findings revealed that many of the bacteria and archaea found in the samples had not been previously recognized or sampled.

For their study, the researchers compared the sequences and assemblies generated from Illuminas short read technology with the data from the newer, longer-read technology that generates read lengths of up around 8,000 base pairs. They found that the longer reads captured more of the communitys diverse species. For instance, using short read technology, they previously identified just over 160 microbial species within a sediment sample. Using the longer-read technology, though, over 400 microbial species from the sample could be phylogenetically classified, though some accounted for just 0.1 percent of the community.

The studys first author, Itai Sharon of UC Berkeley, pointed out that they also identified species that previously failed to assemble due to the presence of closely related species within the sample. These close relatives, accounting for as much as 15 percent of the community, confounded the assembly algorithm. These populations were pretty much missed by the short read assemblies because assemblers tend to fail at the presence of multiple closely related species and strains. Using algorithms that we developed for analyzing the long reads we were able to reconstruct genome architecture for these populations, he said.

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Longer DNA Fragments Reveal Rare Species Diversity

The term "single-nucleotide polymorphism" (SNP) refers to a single base change in DNA sequence between two individuals. SNPs are the most common type of genetic variation in plant and animal genomes and are, thus, an important resource to biologists. The ubiquity of these markers and the fact that these polymorphisms show variation at such a fine scale (i.e., at the individual level) makes them ideal markers for many applications, such as population-level genetic diversity studies and genetic mapping in plants.

The growing popularity of next-generation sequencing has made SNPs a pervasive genetic marker in many areas of plant biology. The ever-increasing throughput of sequencing platforms has resulted in the ability to easily identify and genotype thousands of SNPs across numerous individuals to uncover genetic variation among and within populations. This technique, however, becomes quite challenging when the species of interest has undergone whole genome duplication events (i.e., polyploidy), as is common in many plant lineages.

Researchers at Texas A&M and the Southern Plains Agricultural Research Center have developed a strategy that simplifies the discovery of useful SNPs within the complex genome of cotton. The protocol is freely available in a recent issue of Applications in Plant Sciences.

"Cotton presents a challenge for SNP marker discovery due to the polyploid origin of the two most widely grown species," says Dr. Alan Pepper, an author of the study. "All plants have duplicated sequences, whether due to whole genome duplication, duplication of segments of chromosomes, duplication by retroviruses, or duplication by unequal crossing over. When you are looking for potential SNPs, particularly without a reference genome, you run the risk of identifying sequence differences between duplicated sequences rather than differences between individuals. This problem is particularly acute in recent allopolyploids."

Allopolyploid species are the product of hybridization between two divergent taxa. The genomes of these plants, therefore, contain two very similar copies of their genes--one from each parent.

According to Pepper, "A problem arises when our computational methods accidentally align DNA regions that are duplicated within the genomes of the plants being studied, rather than mapping the orthologous regions between the plants."

Enter the strategy presented by Pepper and colleagues.

Using the Illumina next-generation sequencing platform, over 50 million DNA reads were collected from restriction enzyme-digested DNA from four Gossypium species. The team then filtered these reads to enrich for orthologous DNA fragments.

Pepper explains, "One of the exciting things about this approach is that it employs a widely used, well-supported, off-the-shelf bioinformatics software known as Stacks (written by Julian Catchen at the University of Oregon) as a "filter" to enrich for pairs of fragments that are likely to be alleles of a single, orthologous region, rather than paralogs or homeologs."

The new method allows for the detection of polymorphisms between individuals, which will be useful for downstream applications such as marker-assisted selection, linkage and QTL mapping, and genetic diversity studies.

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Simplifying SNP discovery in the cotton genome

The Deeper Genome
John Parrington, author of The Deeper Genome, looks at the latest research about human DNA and why it is far more complex and more dynamically changing -- than we initially believed. http://ukc...

By: Oxford Academic (Oxford University Press)

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The Deeper Genome - Video

Thyroid Cancer: Biomarkers and Lessons from The Cancer Genome Atlas.Dr. Giordano. ThyCa Conference
241 Biomarkers in Thyroid Cancer: Lessons From The Cancer Genome Atlas (TCGA). 241 Thomas J. Giordano, M.D., Ph.D., Pathologist Biomarkers in Thyroid Cancer: Lessons From The Cancer ...

By: ThyCa: Thyroid Cancer Survivors #39; Association, Inc.

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Thyroid Cancer: Biomarkers and Lessons from The Cancer Genome Atlas.Dr. Giordano. ThyCa Conference - Video

251pp osu! Daidai Genome [Insane] NC
player https://osu.ppy.sh/u/3021716.

By: Res wery

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251pp osu! Daidai Genome [Insane] NC - Video

STI Genome Subaru Legacy B4 2007 BL9 2.5i
STI Genome Subaru Legacy B4 2007 BL9 2.5i Subaru Legacy B4 BLE 3.0 . ...

By: Genome

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STI Genome Subaru Legacy B4 2007 BL9 2.5i - Video