Category Archives: Genome

PUBLIC RELEASE DATE:

28-Nov-2014

Contact: Dr. Patricia Marquardt patricia.marquardt@molgen.mpg.de 49-308-413-1716 Max-Planck-Gesellschaft @maxplanckpress

This news release is available in German.

Humans don't like being alone, and their genes are no different. Together we are stronger, and the two versions of a gene - one from each parent - need each other. Scientists at the Max Planck Institute for Molecular Genetics in Berlin have analysed the genetic makeup of several hundred people and decoded the genetic information on the two sets of chromosomes separately. In this relatively small group alone they found millions of different gene forms. The results also show that genetic mutations do not occur randomly in the two parental chromosome sets and that they are distributed in the same ratio in everyone.

In 2001 scientists announced the successful decoding of the first human genome. Since then, thousands more have been sequenced. The price of a genetic analysis will soon fall below the 1,000 dollar mark. Given this rapid pace of development, it's easy to forget that the technology used only reads a mixed product of genetic information. The analytical methods commonly employed do not take into account the fact that every person has two sets of genetic material. "So they are ignoring an essential property of the human genome. However, it's important to know, for example, how mutations are distributed between the two chromosome sets," says Margret Hoehe from the Max Planck Institute for Molecular Genetics, who carried out the study.

Hoehe and her team have developed molecular genetic and bioinformatic methods that make it possible to sequence the two sets of chromosomes in a human separately. The researchers decoded the maternal and paternal parts of the genome in 14 people and supplemented their analysis with the genetic material of 372 Europeans from the 1000 Genomes Project. "Fourteen people may not sound like a lot, but given the technical challenge, it is an unprecedented achievement," says Hoehe.

The results show that most genes can occur in many different forms within a population: On average, about 250 different forms of each gene exist. The researchers found around four million different gene forms just in the 400 or so genomes they analysed. This figure is certain to increase as more human genomes are examined. More than 85 percent of all genes have no predominant form which occurs in more than half of all individuals. This enormous diversity means that over half of all genes in an individual, around 9,000 of 17,500, occur uniquely in that one person - and are therefore individual in the truest sense of the word.

The gene, as we imagined it, exists only in exceptional cases. "We need to fundamentally rethink the view of genes that every schoolchild has learned since Gregor Mendel's time. Moreover, the conventional view of individual mutations is no longer adequate. Instead, we have to consider the two gene forms and their combination of variants," Hoehe explains. When analysing genomes, scientists should therefore examine each parental gene form separately, as well as the effects of both forms as a pair.

According to the researchers, mutations of genes are not randomly distributed between the parental chromosomes. They found that 60 percent of mutations affect the same chromosome set and 40 percent both sets. Scientists refer to these as cis and trans mutations, respectively. Evidently, an organism must have more cis mutations, where the second gene form remains intact. "It's amazing how precisely the 60:40 ratio is maintained. It occurs in the genome of every individual - almost like a magic formula," says Hoehe. The 60:40 distribution ratio appears to be essential for survival. "This formula may help us to understand how gene variability occurs and how it affects gene function."

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Duality in the human genome

PUBLIC RELEASE DATE:

30-Nov-2014

Contact: Tan Yun Yun tan_yun_yun@a-star.edu.sg 656-826-6273 Biomedical Sciences Institutes (BMSI)

Singapore--Scientists at A*STAR's Genome Institute of Singapore (GIS), in collaboration with local clinicians and colleagues in the USA, have identified a biomarker which is strongly associated with triple negative breast cancer (TNBC), a highly aggressive carcinoma that often has early relapse and metastasis following chemotherapy. The newly identified biomarker, a gene called RASAL2, provides a target for developing new therapeutics designed to treat this often deadly disease.

TNBC is deadly because, unlike other types of breast cancers such as estrogen receptor (ER) positive or HER2 amplified breast tumours which have effective targeted therapy, TNBC tumours do not respond to targeted therapy.

Breast cancer has many subtypes, each with its own genetic makeup. As such, different subtypes behave differently in invasion and metastasis. Using breast cancer cell lines and genomic data from patient samples, molecular biologist Min Feng and her colleagues at the GIS adopted an integrated approach to search for genes whose deregulation may help explain the high metastatic potential of TNBC cells.

Dr Feng found that a small RNA, often called microRNA, is lost in highly metastatic TNBC cells but not in luminal breast cancer. As a result, RASAL2, which is negatively regulated by this microRNA, is up-regulated in a set of TNBC tumours. The study showed that TNBC patients whose tumours have high expression of RASAL2 tend to have a lower survival rate as compared to patients whose tumours have low levels of this gene. Additionally, the study showed that genetic knockdown of RASAL2 gene can lead to reduced metastasis in breast cancer mouse model.

The findings were published recently in the Journal of Clinical Investigation (JCI).

Intriguingly, previous research found that RASAL2 was lost in some of the luminal type of breast tumours, where it acts as a tumour suppressor.

Project leader of the study, Prof Qiang Yu, Senior Group Leader of Cancer Therapeutics and Stratified Oncology Programme at the GIS, said, "Cancer is an extremely heterogeneous disease, where many molecular processes have gone wrong in their own ways. Rather than a tumour suppressor, we show here that RASAL2 actually acts as a cancer promoting molecule in TNBC. This reminds us that the same molecule can function very differently in different subtypes of cancers, a phenomenon which has often been seen before."

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Singapore scientists uncover gene associated with an aggressive breast cancer

PUBLIC RELEASE DATE:

27-Nov-2014

Contact: Rebecca Winkels rebecca.winkels@helmholtz-hzi.de 49-531-618-11403 Helmholtz Centre for Infection Research @Helmholtz_HZI

This news release is available in German.

Genome engineering with the RNA-guided CRISPR-Cas9 system in animals and plants is changing biology. It is easier to use and more efficient than other genetic engineering tools, thus it is already being applied in laboratories all over the world just a few years after its discovery. This rapid adoption and the history of the system are the core topics of a review published in the renowned journal Science. The review was written by the discoverers of the system Prof. Emmanuelle Charpentier, who works at the Helmholtz Centre for Infection Research (HZI) and is also affiliated to the Hannover Medical School and Ume University, and Prof. Jennifer Doudna from the University of California, Berkeley, USA.

Many diseases result from a change of an individual's DNA - the letter code that genes consist of. The defined order of the letters within a gene usually codes for a protein. Proteins are the workforce of our body and responsible for almost all processes needed to keep us running. When a gene is altered, its protein product may lose its normal function and disorders can result. "Making site-specific changes to the genome therefore is an interesting approach to preventing or treating those diseases", says Prof Emmanuelle Charpentier, head of the HZI research department "Regulation in Infection Biology". Due to this, ever since the discovery of the DNA structure, researchers have been looking for a way to alternate the genetic code.

First techniques like zinc finger nucleases and synthetic nucleases called TALENs were a starting point but turned out to be expensive and difficult to handle for a beginner. "The existing technologies are dependent on proteins as address labels and customizing new proteins for any new change to introduce in the DNA is a cumbersome process", says Charpentier. In 2012, while working at Ume University, she described what is now revolutionising genetic engineering: the CRISPR-Cas9 system.

It is based on the immune system of bacteria and archaea but is also of value in the laboratory. CRISPR is short for Clustered Regularly Interspaced Palindromic Repeats, whereas Cas simply stands for the CRISPR-associated protein. "Initially we identified a novel RNA, namely tracrRNA, associated to the CRISPR-Cas9 system, which we published in 2011 in Nature. We were excited when Krzysztof Chylinski from my laboratory subsequently confirmed a long term thinking: Cas9 is an enzyme that functions with two RNAs", says Charpentier.

Together the system has the ability to detect specific sequences of letters within the genetic code and to cut DNA at a specific point. In this process the Cas9 protein functions as the scissors and an RNA snippet as the address label ensuring that the cut happens in the right place. In collaboration with Martin Jinek and Jennifer Doudna, the system could be simplified to use it as a universal technology. Now the user would just have to replace the sequence of this RNA to target virtually any sequence in the genome.

After describing the general abilities of CRISPR-Cas9 in 2012 it was shown in early 2013 that it works as efficiently in human cells as it does in bacteria. Ever since, there has been a real hype around the topic and researchers from all over the world have suggested new areas in which the new tool can be used. The possible applications extend from developing new therapies for genetic disorders caused by gene mutations to changing the pace and course of agricultural research in the future all the way to a possible new method for fighting the AIDS virus HIV.

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Revolutionizing genome engineering

MPG Primer: Genome-wide association studies: past and present
Copyright Broad Institute, 2014. All rights reserved. The Primer on Medical and Population Genetics is a series of informal weekly discussions of basic genet...

By: broadinstitute

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MPG Primer: Genome-wide association studies: past and present - Video

Intelligent flash storage arrays

Most people have heard of the human genome project (HGP), few have yet heard of the human proteome project (HPP) but it is going to transform your life in a far more fundamental way than the HGP never did.

The human genome project was completed in April 2003 - we are currently the only species known to have deciphered its own code. Our genome is the code that defines us. In one sense we all share the human genome, but each of us has our own unique version (which is what makes us individuals and not clones) and a copy is to be found in every cell of our bodies.

Technically, the genome is held in the nucleus of the cell and not all cells have a nucleus (red blood cells do not, for instance), so it's more accurate to refer to every nucleated cell of our bodies". Also, identical twins share genomes so the genome isnt unique for every single individual.

The HGP was a massive effort, excellently documented by Nobel prize winner John Sulston and Georgina Ferry in The Common Thread: A Story of Science, Politics, Ethics and the Human Genome.

Genes are simply the blueprint of the body, so when you become ill, the blueprint isnt affected but your proteins are. Drugs that we take to cure illness or ameliorate symptoms do not work on your genes, they interfere (in a good way) with your proteins

I, and many other people, regard the HGP as one of the major pinnacles of scientific achievement. The guys who did it were working right at the forefront of what could be achieved at the time - both in terms of the biology and the computing. Not only that, they ensured that the rights to the human genome belong to all of us and not to a corporation (it was a close run thing, but read the book for more info.)

The HGP was also heralded as work that would change medicine forever by opening the floodgates for a whole new range of drugs and treatments. So why hasnt this happened yet? The simple answer is that most illnesses dont attack the genome, they attack the proteome.

Whats the proteome? Well, it's the sum total of all of the proteins in your body. So when you look at me you see the proteome not the genome. We can also say that the proteome is the expression of the genome because our genes tell our body what proteins to make and proteins are the functional molecules in a human body.

The genome isnt unique for every single individual (twins), but its still the code that defines us

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Beyond the genome: YOU'VE BEEN DECODED, again

A team of scientists has sequenced the genome of the centipede for the first time and found that it has around 15,000 genes -- about 7,000 fewer than humans do.

Arthropods -- the most species-rich group of animals on Earth -- are divided into four classes, including insects, crustaceans, chelicerates and myriapods. The latter group, which includes centipedes, is the only class for which no genome had yet been sequenced, scientists said in a study, published in the journal PLOS Biology.

With genomes in hand from each of the four classes of living arthropod, we can now begin to build a picture of the genetic make-up of their common ancestor, Frank Jiggins, of the University of Cambridge's genetics department, and one of the researchers involved in the study, said in a statement. For example, by comparing flies and mosquitoes with centipedes, we have shown that the innate immune systems of insects are much older than previously appreciated.

As part of the study, the scientists sequenced the genome of Strigamia maritima, a northern European centipede. They found that its genome is more conserved than that of many other arthropods, such as the fruit fly, suggesting that the centipede has evolved more slowly from their common ancestor. Despite their name, centipedes do not have hundred legs. Strigamia maritima, which lives in coastal habitats, can have between 45 and 51 pairs of legs, but the number of pairs is always odd.

The researchers also discovered that the centipedes have lost the genes encoding all of the known light receptors used by animals, as well as the genes controlling the circadian rhythm, or the body clock.

Strigamia live underground and have no eyes, so it is not surprising that many of the genes for light receptors are missing, but they behave as if they are hiding from the light. They must have some alternative way of detecting when they are exposed, Michael Akam of the University of Cambridge and one of the lead researchers of the study, said in the statement.

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Centipede Genome Sequencing Reveals Animal Has 7K Fewer Genes Than Humans

UW Genome Sciences - Wednesday Evenings at the Genome: Dr. Mary Kuhner
July 16, 2014 "Evolutionary Forensics: Where Did That Come From?"

By: UWGenomeSciences

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UW Genome Sciences - Wednesday Evenings at the Genome: Dr. Mary Kuhner - Video

UW Genome Sciences - Wednesday Evenings at the Genome: Dr. George Martin
July 10, 2013 "How Nature, Nurture and Chance Shapes How We Age"

By: UWGenomeSciences

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UW Genome Sciences - Wednesday Evenings at the Genome: Dr. George Martin - Video

Centipedes, those many-legged creatures that startle us in our homes and gardens, have been genetically sequenced for the first time. In a new study in the journal PLOS Biology, an international team of over 100 scientists today reveals how this humble arthropod's DNA gave them new insight into how life developed on our planet.

Centipedes are members of the arthropods, a group with numerous species including insects, spiders and other animals. Until now, the only class of arthropods not represented by a sequenced genome was the myriapods, which include centipedes and millipedes. For this study, the researchers sequenced the genome of the centipede Strigamia maritima, because its primitive features can help us understand more complex arthropods.

According to Prof. Ariel Chipman, senior co-author of the study and project leader at the Hebrew University of Jerusalem's Alexander Silberman Institute of Life Science, the genetic data reveal how creatures transitioned from their original dwelling-place in the sea to living on land.

"The use of different evolutionary solutions to similar problems shows that myriapods and insects adapted to dry land independently of each other," said Chipman. "For example, comparing the centipede and insect genomes shows that they independently evolved different solutions to the same problem shared by all land-dwelling creatures -- that of living in dry air."

According to Chipman, the study found that despite being closely related to insects, the centipede lacks the olfactory gene family used by insects to smell the air, and thus developed its own air-sniffing ability by expanding other gene families not present in insects.

In addition, Chipman said, this specific group of centipedes live underground and have lost their eyes, together with almost all vision genes and genes involved in the body's internal clock. They maintain enhanced sensory capabilities enabling them to recognize their environment and capture prey.

Published in the latest edition of PLOS Biology, the research is a collaborative effort by over 100 scientists from 50 institutions. Thousands of human-hours went into looking at specific genes in the centipede genome, with each researcher looking at a limited set of genes or at specific structural characteristics to address specific questions.

Other leaders of the international research effort include Dr. Stephen Richards, Baylor College of Medicine; Dr. David Ferrier, University of St. Andrews; and Prof. Michael Akam of Cambridge University. The research paper is titled "The First Myriapod Genome Sequence Reveals Conservative Arthropod Gene Content and Genome Organisation in the Centipede Strigamia maritima."

While early studies of genomics focused on humans, as sequencing equipment and expertise became more readily available, researchers expanded into animals directly relevant to human wellbeing. In the latest research, genomic sequencing has become more broad-based, investigating the workings of the world around us.

In explaining the purpose of the research, Hebrew University's Chipman said: "If we have a better understanding of the biological world around us, how it operates, and how it came to be as it is, we will ultimately have a better understanding of ourselves."

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Centipede's genome reveals how life evolved on our planet

By Geoffrey Giller

Researchers have sequenced the genome of a rare, ten centimetre-long, ribbon-shaped tapeworm that had been travelling through a man's brain for four years in a move that could lead to new treatments for tapeworm infections.

Tapeworms usually infect the gut, causing symptoms such as weakness, weight loss and abdominal pain. But the larvae of some species can reach the eyes, brain and spinal cord. The species in this case, Spirometra erinaceieuropaei, is one such parasite.

Human infections caused by the larvae from this and closely related species are known as sparganosis. Although these species are found worldwide, such medical cases are most common in Asian countries such as China, Japan, South Korea and Thailand.

Other tapeworm species have a greater worldwide impact, for example causing neglected tropical diseases such as seizure-causing neurocysticercosis and potentially fatal alveolar echinococcosis.

In the case at the heart of the new research, a man of Chinese ethnicity living in the United Kingdom but who frequently visited China sought treatment in 2008, complaining about headaches, seizures, memory loss and occasional episodes of altered smell.

An MRI scan showed small lesions in the man's brain. However, numerous tests for everything from HIV to tuberculosis came back negative.

Doctors monitored the lesions for four years and found something strange: they moved around. Only when doctors operated on the man in 2012 did they discover the ten centimetre-long tapeworm living in his head.

The reason it took so long to diagnose, says Hayley Bennett, a researcher at the Wellcome Trust Sanger Institute, United Kingdom, and the lead author of a paper on the research published last week (21 November) in Genome Biology, is that infection by this particular type of worm is exceedingly rare.

"That was the first time this worm has ever been seen in the UK," she says. "I think the clinicians were pretty surprised."

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Africa: Genome of Tapeworm Found in Man's Brain Sequenced