Category Archives: Genome

Public release date: 22-May-2013 [ | E-mail | Share ]

Contact: Pr Ingvarsson par.ingvarsson@emg.umu.se 46-708-485-977 Umea University

Swedish scientists have mapped the gene sequence of Norway spruce (the Christmas tree) a species with huge economic and ecological importance - and that is the largest genome to have ever been mapped. The genome is complex and seven times larger than that of humans. The results have been published in the prestigious journal Nature.

This major research project has been led by Ume Plant Science Centre (UPSC) in Ume and the Science for Life Laboratory (SciLifeLab) in Stockholm.

In addition to its scientific interest this new knowledge has immense importance to the forestry industry in many countries.

"Forest tree breeding is now entering a new era, and Sweden has the potential to be in the forefront of development," says Professor Ove Nilsson from UPSC. "Newer and more effective methods can begin to be used to ensure that the over 200 million tree seedlings planted each year in Sweden are as strong, healthy and well-adapted as possible for both poor and rich soil areas in different parts of the country."

The scientists have identified about 29,000 functional genes, marginally more than humans have, but the question arises: why is the spruce genome still seven times larger than ours? According to the study an explanation is "genome obesity" caused by extensive repetitive DNA sequences, which have accumulated for several hundred million years of evolutionary history. Other plant and animal species have efficient mechanisms to eliminate such repetitive DNA, but these do not seem to operate so well in conifers.

"It is remarkable that the spruce is doing so well despite this unnecessary genetic load," says Professor Pr Ingvarsson at UPSC. "Of course, some of this DNA has a function but it seems strange that it would be beneficial to have so very much. This appears to be something special for conifers."

The greatest challenge in the project has been to get the approximately 20 billion "letters" found in spruce's genetic code into the correct order, rather than obtaining the actual DNA sequences.

"Imagine a library with ten thousand books as thick as the bible, written in a language with only four letters," explains Professor Stefan Jansson at UPSC. "If someone took one hundred identical copies of each of the ten thousand titles, passed them all through a document shredder and mixed all the shreds, and you then were asked to piece together an accurate copy of each title, you can realize that it can be a bit problematic."

Read the rest here:
The Norway spruce genome sequenced

Relatives of the Norway spruce are some of the oldest living things on the planet. They haven't used all that time to tidy up their genomes, though.

Last week we heard about the genome of a plant that pushed the limits of compacting its DNA:the bladderwortseems to have done away with of most of the genetic material that typically makes plant and animal genomes so large without any apparent ill effects. This week, the genome of a different plant is in the spotlight:the Norway spruce (Picea abies), which also seems to suffer no ill effects, even though it has picked up an enormous amount of DNA. Each one of its chromosomes is nearly the size of the entire human genomeand it has a dozen of them. When researchers looked at what all that extra DNA might be doing, they came up with a simple answer: probably not anything useful.

If you're aware of the Norway spruce, it's probably because you have been shopping for a Christmas tree. But conifers (technically Gymnosperms, although the group includes gingkoes and a few other species) are some of the most phenomenally successful organisms on Earth. They've dominated forests for over 200 million years, and members of the group include the tallest, heaviest, and oldest things currently alive. All of them seem to have managed this despite having a staggeringly inefficient genome management style.

Unlike many groups that vary widely in the number of chromosomes their species carry, pretty much all the Gymnosperms have a dozen pairs of chromosomes. And pretty much all of these chromosomes are up in the area of two billion bases long, or a bit smaller than the human genome. That size is so consistent, in fact, that the authors think the trees might be pushing up against the limits of how much stuff you can put in a chromosome and still get it copied and shared between two cells when they divide. In other words, if firs wanted to carry any more DNA than they already do, they'd have to start making new chromosomes.

From an evolutionary fitness perspective, would the plants actually want more DNA? Probably not, if the new genome is anything to go by. Despite all the extra DNA, the Norway spruce has almost exactly the same number of genes28,354 in totalthat the bladderwort does, even though the latter has about 1/250th the DNA. But it has plenty of dead copies of genes that have been inactivated by mutation. All told, these pseudogenes take up over seven times as much space in the genome as the working genes do.

However, the pseudogenes are a small contributor to the size of the genome compared to mobile genetic parasites called transposons. The transposons have hopped into all sorts of places in the genomewithin the non-coding introns of genes, in between genesand just stayed there. In fact, the Norway Spruce has an unusually high number of large introns simply because so many of them have picked up one or more transposons. Based on looking at a number of other Gymnosperms, these transposons have just been slowly accumulating throughout the group's history and have just never gone away, "possibly owing to the lack of an efficient elimination mechanism. "

Inaccurate recombination between chromosomes can sometimes create deletions, which might get rid of some of the excess DNA once it's present. But the conifers don't undergo recombination very often in the areas where that DNA residesinstead, the exchange of DNA mostly happens where the genes are.All told, the authors call this a "one way ticket toward genome obesity."

Incidentally, all this stuff made sequencing the genome a nightmare. Normally, software is used to recognize when two stretches of sequence partly overlap because the sequence is identical, and it uses further overlaps to build ever-larger sequences. In this case, the frequency of transposons meant that there were nearly identical sequences scattered everywhere in the genome. Imagine trying to build a city map where every road that ran north-to-south had a name, but everything east-west was simply called "street." To cope with this, the team separated out chunks of the chromosome a few hundred thousand bases long, figured out the sequence of the chunk, and then looked for places where the chunks overlapped. This method got the job done, but there are still plenty of gaps and missing sequences.

There are a few other draft conifer genomes in the works and all of them pretty much look like this, although the exact details of which transposons are present and where they're located differ somewhat among the species. So far, the genomes only tell us a little about the origin of the features we commonly associate with trees. But they definitely tell us that a group of species don't have to be neat freaks in order to be phenomenally successful.

Nature, 2013. DOI: 10.1038/nature12211 (About DOIs).

Read the original post:
Pines punched a “one way ticket toward genome obesity”

We generated >1 billion RNA-Seq reads and used transcript assemblies of these in combination with public expressed sequence tags (ESTs) and transcripts to perform ab initio prediction of protein-coding genes, which identified a high confidence set of 28,354 loci with >70% coverage by supporting evidence from the total set of 70,968 predicted loci. A notable characteristic of the predicted gene structures was the presence of numerous long introns (Fig. 1b), with mean intron length being higher than in most available plant genomes, although similar to the repeat-rich genomes of Vitis vinifera and Zea mays17, 18. The longest intron in the high-confidence genes was 68kb (Supplementary Table 2.6), and 2,384 high-confidence genes contained 2,880longer than5-kb introns (20 of which we confirmed by PCR amplification; Supplementary Information 2.14), 2,679 of which contained a repeat, suggesting that repeat insertions account for intron expansion. By contrast, exon size was consistent among the species considered (Supplementary Information 2.6.3). Numerous genes (~30%) remained split across scaffolds owing to assembly fragmentation, and as such, the longest introns were not represented in the P.abies 1.0 assembly. Long introns (either individual or cumulative intron length) did not influence expression levels (Fig. 1c) and introns containing repeats have not contracted despite a lack of recent repeat activity (see below).

a, Gene family loss and gain in eight sequenced plant genomes (Arabidopsis thaliana, Populus trichocarpa, Vitis vinifera, Oryza sativa, Zea mays, Picea abies, Selaginella moellendorffii and Physcomitella patens). Gene families were identified using TribeMCL (inflation value 4), and the DOLLOP program from the PHYLIP package was used to determine the minimum gene set for ancestral nodes of the phylogenetic tree. We used plant genome annotations filtered to remove transposable elements. Orphans refers to gene families containing only a single gene. Blue numbers indicate the number of gene families. b, Boxplot representation of length distribution for the 10% longest introns in the same eight genomes. c, Scatter plots of cumulative intron length against log10 expression calculated as fragments per kilobase per million mapped reads (FPKM) for high-confidence gene loci (top, coloured orange) and green for lncRNA loci (middle, shaded green). The bottom panel shows a histogram of cumulative intron size in the two sets of loci. d, Distribution of small (1824-nucleotide (nt)) RNAs and their co-alignment-based colocation to genomic features (repeats, high-confidence genes and their promoter/UTRs). CDS, coding sequence.

Analysis of gene families in the high-confidence gene set and seven sequenced plant genomes (five angiosperms: Arabidopsis thaliana, Populus trichocarpa, Vitis vinifera, Oryza sativa and Zea mays, and two basal plants: Selaginella moellendorffii and Physcomitrella patens) identified 1,021 P. abies-specific gene families (Fig. 1a and Supplementary Information 2.8). P. abies-specific families included over-representation of Gene Ontology categories involved in DNA repair and methylation of DNA and chromatin (Supplementary Information 2.8). As for most draft genomes, these results probably overestimate gene numbers19 and will be refined as we further improve the genome assembly.

A common mechanism leading to genome size expansion is the occurrence of a whole genome duplication (WGD) event. We calculated the number of synonymous substitutions per synonymous site (Ks) of paralogues within the high-confidence genes but found no evidence for any recent WGD; there was a clear, exponential decay in the number of retained paralogues with increasing Ks values (Supplementary Information 2.9 and Supplementary Fig. 2.6). However, a population dynamics model that takes into account both small- and large-scale modes of gene duplication20 suggested the presence of a small peak (around Ks of 1.1), which, considering the slow substitution rate of conifers, might represent the ancient WGD predating the divergence of angiosperms and gymnosperms (350Myr ago21).

Previous examinations of small genomic subsets indicated that conifer genomes contain numerous pseudogenes5, 6, 22, 23. The gene-like fraction of the P.abies 1.0 assembly was identified by alignment of RNA-Seq reads and de novo assembled transcripts (Supplementary Information 2.10). Within this subset of the genome, loci with valid spliced alignments of de novo assembled transcripts or the presence of a high-confidence gene were also identified. The high-confidence gene set represented 27Mb of protein-coding sequence, whereas 72Mb of regions were identified with a valid spliced alignment or a high-confidence gene. In stark contrast, 524Mb of gene-like regions were identified by less stringent alignments. The presence of such a large gene-like fraction lacking predicted gene structures supports the presence of numerous pseudogenes.

Recent ENCODE publications24, 25 characterized numerous long non-coding RNA (lncRNA) loci in the human genome, but this class of RNA remains largely uncharacterized in plants. Using short-read de novo transcript assemblies, 13,031 spruce-specific and 9,686 conserved intergenic lncRNAs were identified (Supplementary Information 2.4.3). In common with the ENCODE results, P. abies lncRNA loci contained fewer exons, were shorter (Fig. 1c), and had more tissue-specific expression than protein-coding loci (Supplementary Fig. 2.8).

There has been conflicting evidence about the presence of 24-nucleotide short RNAs (sRNAs) in gymnosperms26, 27, 28, 29, a class of sRNA that silence transposable elements by the establishment of DNA methylation30. Across 22 samples, we identified numerous 24-nucleotide sRNAs, but these were highly specific to reproductive tissues, largely associated with repeats but present at substantially lower levels than in angiosperms (Fig. 1d and Supplementary Fig. 2.10). By contrast, 21-nucleotide sRNAs were associated with genes, repeats and promoters/untranslated regions (UTRs) (Fig. 1d). De novo microRNA (miRNA) prediction identified 2,719 loci, including 20 known miRNA families, with target sites predicted within the high-confidence gene set for 1,378 of these (Supplementary Information 2.13). Furthermore, 55 known miRNA families had >5 aligned sRNA reads and mature miRNAs, representing 49 known families aligned to the genome (Supplementary Information 2.13).

Read the original:
The Norway spruce genome sequence and conifer genome evolution

May 22, 2013 Swedish scientists have mapped the gene sequence of Norway spruce (the Christmas tree) -- a species with huge economic and ecological importance -- and that is the largest genome to have ever been mapped. The genome is complex and seven times larger than that of humans.

The results have been published in the journal Nature.

In addition to its scientific interest this new knowledge has immense importance to the forestry industry in many countries.

This major research project has been led by Ume Plant Science Centre (UPSC) in Ume and the Science for Life Laboratory (SciLifeLab) in Stockholm.

"Forest tree breeding is now entering a new era, and Sweden has the potential to be in the forefront of development," says Professor Ove Nilsson from UPSC. "Newer and more effective methods can begin to be used to ensure that the over 200 million tree seedlings planted each year in Sweden are as strong, healthy and well-adapted as possible for both poor and rich soil areas in different parts of the country."

The scientists have identified about 29,000 functional genes, marginally more than humans have, but the question arises: why is the spruce genome still seven times larger than ours? According to the study an explanation is "genome obesity" caused by extensive repetitive DNA sequences, which have accumulated for several hundred million years of evolutionary history. Other plant and animal species have efficient mechanisms to eliminate such repetitive DNA, but these do not seem to operate so well in conifers.

"It is remarkable that the spruce is doing so well despite this unnecessary genetic load," says Professor Pr Ingvarsson at UPSC. "Of course, some of this DNA has a function but it seems strange that it would be beneficial to have so very much. This appears to be something special for conifers."

The greatest challenge in the project has been to get the approximately 20 billion "letters" found in spruce's genetic code into the correct order, rather than obtaining the actual DNA sequences.

"Imagine a library with ten thousand books as thick as the bible, written in a language with only four letters," explains Professor Stefan Jansson at UPSC. "If someone took one hundred identical copies of each of the ten thousand titles, passed them all through a document shredder and mixed all the shreds, and you then were asked to piece together an accurate copy of each title, you can realize that it can be a bit problematic."

"We had to customise computers and rewrite many of the computer programmes used in similar studies in order to handle the large amount of DNA sequences," says Professor Joakim Lundeberg from SciLifeLab. The national data storage system was stretched to the limit, and there were many other practical problems that had to be solved along the way to pull through the project.

Read the original:
Norway spruce genome sequenced: Largest ever to be mapped

Future of Me: Your Accessible Genome
Advances in gene sequencing technologies plus increased computer capacity for information analysis means we are on the verge of being able to access and unde...

By: TheBridge8

See the original post:
Future of Me: Your Accessible Genome - Video

The population of Ireland has yet to rebound from the deaths and migrations caused by the famine of mid-19th-century.

James Mahony/Wikimedia Commons

The great potato famine of the 1840s was a defining event in Irelands recent history. An Gorta Mr the Great Hunger in the Irish language caused millions to starve or emigrate and helped catalyse the countrys bloody war of independence from Great Britain.

Working from 150-year-old dried leaves, two competing teams have now sequenced the genome of the single-celled organism that wreaked havoc on the Irish potato crop. It is the first ancient plant pathogen to have its genome decoded. (In 2011, scientists reported the sequence of the plague-causing bacteria responsible for the Black Death of the 1340s.)

Phytophthora infestans, which causes potato late blight, is an oomycete a type of single-celled organism related to brown algae. Carried by infected potatoes, the disease probably arrived at the port of Antwerp in Belgium in the summer of 1845, before quickly spreading through the Low Countries and much of western Europe.

Irelands dependence on potatoes was the reason the epidemic exacted a far greater toll there than it did on the rest of the continent. Irish peasants working plots owned by absentee British landlords relied on potatoes for most of their calories, says Detlef Weigel, a plant geneticist at the Max Planck Institute for Developmental Biology in Tbingen, Germany, who co-led a study published today in the journal eLIFE1. The potato is really an amazing staple crop. If you have a diet of potato and milk, you dont need anything else.

The disappearance of that staple had devastating consequences, including 1 million deaths and still more emigrations. Irelands population of 4.5 million is still less than three-quarters of its pre-famine level. The perception that Britain did little to intervene in the catastrophe helped foment Irish nationalism, eventually resulting in the Irish War of Independence in 1919.

Long before it hit Europe, P. infestans probably circulated in the Toluca Valley in central Mexico, where it infected wild relatives of the potato. Until recently, only a single strain of P. infestans, dubbed US-1, plagued potatoes outside Mexico and South America. So it came as a surprise when, in 2001, scientists suggested that a different strain was responsible for the famine, after analysing a short stretch of P. infestans DNA from herbarium archives2.

Weigels team went to herbaria in Kew Gardens, outside of London, and at Germanys Botanische Staatssammlung in Munich and sequenced DNA preserved from the dried leaves of infected plants dating between 1845 and 1896.

Mitochondrial genomes from the famine strains showed they were more closely related to the US-1 strain than the earlier research suggested, and that the two strains diverged only in the early 1800s. Weigel says the split probably occurred in the United States, before the strain responsible for the famine was imported to Europe. That strain now appears to be extinct, or perhaps restricted to small pockets of the world.

See the original post:
Pathogen genome tracks Irish potato famine back to its roots

Striking a blow at foodborne diseases, the 100K Pathogen Genome Project at UC Davis Tuesday announced that it has sequenced the genomes of its first 10 infectious microorganisms, including strains of Salmonella and Listeria.

"We are creating a free, online encyclopedia or reference database of genomes so that during a foodborne disease outbreak, scientists and public health professionals can quickly identify the responsible microorganism and track its source in the food supply using automated information-handling methods," said Professor Bart Weimer, director of the 100K Genome Project and co-director of BGI@UC Davis, the Sacramento facility where the sequencing is carried out.

Weimer estimates that the availability of this genomic information will cut in half the time necessary to diagnose and treat foodborne illnesses, and will enable scientists to make discoveries that can be used to develop new methods for controlling disease-causing microorganisms in the food chain.

The project is dedicated to sequencing the genomes of 100,000 bacteria and viruses that cause serious foodborne illnesses in people around the world.

In the United States alone, foodborne diseases annually sicken 48 million people and kill 3,000, according to the Centers for Disease Control and Prevention.

The initial 10 genome sequences mark the first in a series that the

"This initial release validates the entire process, from start to finish, of acquiring the bacterium, producing the genome sequence, and making automated public releases," Weimer said.

A genome is the complete collection of an organism's hereditary information.

Weimer said that the 100K Genome Project currently is sequencing a second set of 1,500 microbial genomes, with an anticipated release in the fall of 2013.

The 100K Genome Project was launched in March 2012 as a collaborative effort between UC Davis, Agilent Technologies, and the U.S. Food and Drug Administration. Since then, the U.S. Centers for Disease Control and Prevention, Department of Agriculture, and National Institutes of Health, as well as seven corporate partners, have joined the worldwide effort. For more information visit http://100kgenome.vetmed.ucdavis.edu.

Go here to see the original:
100K Pathogen Genome Project maps first genomes at UC Davis

DAVIS Striking a blow at foodborne diseases, the 100K Pathogen Genome Project at the University of California, Davis, today announced that it has sequenced the genomes of its first 10 infectious microorganisms, including strains of Salmonella and Listeria.

We are creating a free, online encyclopedia or reference database of genomes so that during a foodborne disease outbreak, scientists and public health professionals can quickly identify the responsible microorganism and track its source in the food supply using automated information-handling methods, said professor Bart Weimer, director of the 100K Genome Project and co-director of BGI@UC Davis, the Sacramento facility where the sequencing is carried out.

Weimer estimates that the availability of this genomic information will cut in half the time necessary to diagnose and treat foodborne illnesses, and will enable scientists to make discoveries that can be used to develop new methods for controlling disease-causing microorganisms in the food chain.

The project is dedicated to sequencing the genomes of 100,000 bacteria and viruses that cause serious foodborne illnesses in people around the world.

In the United States alone, foodborne diseases annually sicken 48 million people and kill 3,000, according to the Centers for Disease Control and Prevention.

The initial 10 genome sequences mark the first in a series that the project will enter into a publicly available database at the National Center for Biotechnology Information of the National Institutes of Health.

This initial release validates the entire process, from start to finish, of acquiring the bacterium, producing the genome sequence, and making automated public releases, Weimer said.

A genome is the complete collection of an organisms hereditary information.

Weimer said that the 100K Genome Project currently is sequencing a second set of 1,500 microbial genomes, with an anticipated release in the fall of 2013.

The 100K Genome Project was launched in March 2012 as a collaborative effort between UC Davis, Agilent Technologies, and the U.S. Food and Drug Administration. Since then, the U.S. Centers for Disease Control and Prevention, Department of Agriculture, and National Institutes of Health, as well as seven corporate partners, have joined the worldwide effort. For more information visit http://100kgenome.vetmed.ucdavis.edu.

Go here to see the original:
100K Pathogen Genome Project maps first genomes

BALTIMORE, May 21, 2013 /PRNewswire/ --Personal Genome Diagnostics Inc. (PGDx), today announced that it will use its proprietary methodologies and expertise in genomic analysis of defined cancer subtypes to identify novel kinase targets in collaboration with Blueprint Medicines. PGDx is an innovator in conducting patient-specific analyses aimed at identifying genomic alterations in tumors, and Blueprint Medicines is an expert in developing highly selective kinase inhibitors for a genetically defined patient population.

"This collaboration brings together two companies that are at the forefront of applying advanced genomics to improve cancer therapy," said Antony Newton, chief commercial officer of PGDx. "Blueprint is a leader in identifying novel targets and developing highly selective kinase inhibitors for specific genomically-defined patient populations, and PGDx has unique capabilities to identify kinase and other tumor-specific alterations."

PGDx leverages the deep expertise of its scientific founders, who are internationally recognized leaders in cancer genomics at Johns Hopkins University, and its proprietary technologies to provide advanced genome-mapping services and analyses to oncology researchers, drug developers and clinicians. The founders of PGDx were the first to analyze the entire set of kinase genes in tumors, the "kinome", and have identified alterations in a variety of protein and lipid kinases, including the discovery of alterations in PIK3CA, one of the most frequently mutated genes in human cancer. PGDx has also been a pioneer in enabling scientists and clinicians to comprehensively analyze entire exomes and genomes to identify novel cancer alterations.

"We are assessing a series of cancer subtypes that have not been examined before and look forward to working with PGDx to identify new and important aberrations," commented Dr. Christoph Lengauer, chief scientific officer of Blueprint Medicines. "Our goal of identifying key genomic drivers of cancer and leveraging these insights to develop the next generation of highly selective and tailored kinase inhibitors aligns well with PGDx's focus."

Blueprint Medicines is building a pipeline of next-generation kinase inhibitors against specific genetic abnormalities. Using their significant expertise in cancer genomics and biology, Blueprint has built a proprietary genomics platform to rapidly identify novel targets and potential combination therapies. Blueprint is able to rapidly execute on newly-identified targets using their broad and exquisitely selective chemical library of novel kinase inhibitor compounds.

As part of the collaboration, PGDx will employ a number of technologies including cancer exome analysis to capture and selectively analyze tumor sequences. These approaches, when combined with other patented PGDx technologies and computational methods, enable comprehensive analysis and unbiased detection of novel cancer-related mutations.

About Personal Genome Diagnostics

Personal Genome Diagnostics (PGDx) provides advanced genome-mapping services and analyses to oncology researchers, clinicians and patients. The company was founded in 2010 by international leaders in cancer genetics at Johns Hopkins University. PGDx conducts patient-specific analyses aimed at identifying the unique genomic alterations in tumors and linking them to the underlying biology. PGDx employs cancer exome analysis, which enables comprehensive and reliable genome-wide identification of cancer-related mutations. The company's proprietary methods for genome sequencing and analysis are complemented by its deep expertise in cancer genomics. PGDx's CLIA-certified facility provides personalized cancer genome analyses to patients and their physicians. For more information, visit http://www.personalgenome.com.

About Blueprint Medicines

Blueprint Medicines is a patient-driven company building a pipeline of exquisitely selective and tailored next-generation kinase drugs against genetic abnormalities. Using the molecular blueprint of genetically-defined patient populations and a proprietary genomics platform, Blueprint is rapidly identifying novel targets and combinations. Blueprint deploys a chemical library of novel compounds that covers a majority of the human kinome, as highly selective starting points for drug development programs as well as tool compounds. Blueprint Medicines was founded by a proven team, including the developers of Gleevec, and is backed by leading venture firms, Third Rock Ventures and Fidelity Biosciences. For more information, please visit the company's website at http://www.blueprintmedicines.com.

Here is the original post:
Personal Genome Diagnostics And Blueprint Medicines Form Collaboration to Identify Novel Kinase Targets

Fred Alt: Immunity and stability in the human genome
Frederick Alt, a Professor of Genetics and Pediatrics at Harvard Medical School, is one of the Heads of Faculty for Immunology at F1000Prime. Professor Alt t...

By: Facultyof1000

Read the original post:
Fred Alt: Immunity and stability in the human genome - Video