Pathways to smoking behaviours: biological insights from the Tobacco and Genetics Consortium meta-analysis

Pathways to smoking behaviours: biological insights from the Tobacco and Genetics Consortium meta-analysis




          By running gene and pathway analyses for several smoking behaviors in the Tobacco and Genetics Consortium (TAG) sample of 74 053 individuals, 21 genes and several chains of biological pathways were implicated. Analyses were carried out using the HYbrid Set-based Test (HYST) as implemented in the Knowledge-based mining system for Genome-wide Genetic studies software. Fifteen genes are novel and were not detected with the single nucleotide polymorphism-based approach in the original TAG analysis. For quantity smoked, 14 genes passed the false discovery rate of 0.05 (corrected for multiple testing), with the top association signal located at the IREB2 gene (P=1.57E-37). Three genomic loci were significantly associated with ever smoked. The top signal is located at the non-coding antisense RNA transcript BDNF-AS (P=6.25E-07) on 11p14. The SLC25A21 gene (P=2.09E-08) yielded the top association signal in the analysis of smoking cessation. The 19q13 noncoding RNA locus exceeded the genome-wide significance in the analysis of age at initiation (P=1.33E-06). Pathways belonging to the Neuronal system pathways, harboring the nicotinic acetylcholine receptor genes expressing the α (CHRNA 1-9), β (CHRNB 1-4), γ, δ and ε sub-units, yielded the smallest P-values in the pathway analysis of the quantity smoked (lowest P=4.90E-42). Additionally, pathways belonging to ‘a subway map of cancer pathways’ regulating the cell cycle, mitotic DNA replication, axon growth and synaptic plasticity were found significantly enriched for genetic variants in ever smokers relative to never smokers (lowest P=1.61E-07).
          This article was interesting to me because it was relating genes to smoking and to cancer. It talked about genes in smokes versus non-smokers and how smoking can lead to cancer. It was very cool to find out the genomic loci were associated with people who smoked.

Microbes With Limited DNA May Reveal Secrets of Life

Scientists recently deleted nearly half the genes in a microbe, which created a stripped-down version that still fully functions. This achievement can potentially reveal secrets of life and how life works. This finding may also help researchers create new bacteria specially made for pumping out medicine and other valuable substances. 

This newly created bacterium contains less genetic information than any other natural free-living counterpart. This bacterium had 531,000 DNA building blocks, and 473 genes, while humans have more than three billion DNA building blocks, and more than 20,000 genes. Unfortunately, scientists still consider this simple microbe as a mystery, because they are still unsure what one third of their genes actually do. 

Some of these mystery genes could possibly reveal unknown fundamental processes of life, which Clyde Hutchinson III and J. Craig Venter said in an interview, the two authors of a paper on the project release in the journal Science. The brand new genome, or DNA code, is contained in a brand new bacterium called JCVI-syn3.0. 

This is not the only set of minimal genes needed for life itself. If the researchers had paired DNA from a different bacterium, they probably would have gotten a different set of genes. The minimum genome an organism needs would depend on its environment in which it lives. Additionally, the genome includes genes that are not essential to life, because they help the bacteria populations grow fast and this makes it easy for lab work. 

A goal of this work is to find out what every single gene living cell does, which would give a very good understanding of how cells work and function. Another goal is to use minimal-DNA microbes as a chassis for adding genes to make the organisms produce medicines, and other substances for uses like nutrition and agriculture. 

This work began with a man-made version of a microbe found in sheep, called M. mycoides, which has about 900 genes. The scientists identified 428 non-useful genes, and built their genome without it but was still complete enough to let the bacterium survive. 

I believe this work is only the beginning to a huge finding in genetics. With this information, scientists can get closer to defining each and every gene in a living cell and understand what the function is of each. It is hard to believe that more than half of the genes in a microbe could be non-essential, yet not understood. With this study, there will be advances in medicine and public health research. 

New Lightweight Champion of Genomes

Chris Venter, a genome sequencing pioneer of San Diego, California, and his team have released a report describing their recently engineered bacteria with the smallest genome of any freely living organism ever recorded.

This synthetic organism has been strapped down to only the bare minimum of potentially the only genes necessary to survive and reproduce. Unlike the genome of 20,000-25,000 possessed by humans, or the heavyweight champion Japanese flower that is comprised of 50 times more DNA than humans, this new bacteria known as Syn. 3.0 is comprised of only an astounding 473 genes.Venter's previous work had created the Syn 1.0, which had a genome of 901. In an attempt to shrink the genome smaller than the leading minimal genome of 525 in Mycoplasma genitalium, Vetner's large team of colleagues broke up into teams for each section of the bacteria's genome and kept stripping genes from Syn 1.0 with functions that were either nonessential or duplicated the function of another gene until they had a viable organism with a smaller genome than the previous leader.   

Venter claims him and his team designed and tested "multiple hundreds" of constructs until they settled on Syn 3.0. Compared to M. genitalium which can take weeks for a population of its cells to double, Syn 3.0's slimmed down genome is able to double in 3 hours. The function of 149 of Syn 3.0's 473 genes still remain unknown, which leads way to further investigations and insights into the basic biology of life. Evolutionary biologists and biotechnologists are claiming to also start adding genes back to the genome of 3.0 to study their effects. 

This is extremely exciting stuff, as it basically tells us that biologists have been paved a path for new discoveries. Syn 3.0 seems like the key to a new doorway of genetics which could potentially help lead to discoveries that just might end up in the school textbooks of the future. 

  

You Share 70% of Your Genes with This Slimy Worm

Many of us do not realize how much we may have in common with some creatures that are found in the deep blue sea. After researchers observed the sequenced genomes from two marine worm species, it had been suggested that humans and acorn worms may be distant cousins. When analyzing the genes from two acorn worm species, it was discovered that acorn worms share about 14,000 genes with humans, comprising approximately 70 percent of the human genome. Not only do these genes exist in humans, but also in deuterostomes such as sea stars, cephalopods, and various other animals with backbones. The 570 year old acorn worms are able to help scientists understand how genes that first appeared almost hundreds of millions of years ago control the development of different, but related physical features across animal species. Additionally, after the sequencing of the worms' genomes, scientists found 8,716 gene families in the acorn worms that are shared across all deuterostomes. There was one unique family that contained a gene cluster that was linked to feeding and breathing in acorn worms, and scientists were interested because acorn worms have special slits that they use for feeding and allow water to pass through the worm's mouth, but pass it's digestive tracts. It was found that these genes could possibly be linked to gill development and even these genes could play a role in the development of the pharynx. I believe it is truly amazing that we can have a large amount genes connected to a worm found in the sea. I still think more research should be done  before we get so excited to call acorn worm our cousin, but the breakthroughs we are capable of in this generation is riveting.

Link to this article:

http://news.discovery.com/human/genetics/you-share-70-of-your-genes-with-this-slimy-worm-151119.htm

Link to alternate article:

http://www.dispatchreview.com/slimy-marine-worm-shares-70-of-your-genes/2249/

New Parents Favor In-depth Genetic Testing

A Boston survey found that new parents are interested in having their newborn baby undergo in-depth genetic screening to learn about potential health risks.  Newborn babies currently get blood tests that screen for about 30 heritable and treatable conditions. The researcher's found that 83% of parents surveyed within the first 2 days of their baby's birth were interested in in-depth genetic testing for their baby. In-depth genetic screening is also well known as genomic testing, which has the potential to provide more comprehensive personal information than normal blood tests. The parents who took the survey were all similar regardless of age, gender, race, ethnicity, level of eduction, family history of genetic disease, or if it was their first child.

Harvard found that as whole-exome and genome sequencing is integrated into clinical practice, researchers are becoming more interested in providing in-depth health information for newborns that is not already known from standard blood screenings.
I believe advancements in newborn genetic testings is a step in the right direction. If parents find out the genetic sequence of their child at birth that can help treat a medical condition before it gets out of hand.



Article: http://health.usnews.com/health-news/articles/2014/12/04/new-parents-favor-in-depth-genetic-testing-survey-finds

Genetic Match? People Marry Those With Similar DNA

New research supports the idea that people tend to pick spouses in which their genetic profile is similar to their own. Based on the journal Proceedings of the National Academy of Sciences, mating isn't truly genetically random. Benjamin Domingue from the University of Colorado, analyzed genetic information from 825 non-Hispanic white american and found that married people have more similar DNA segments than random pairs of people. It was found that people tend to marry others who are similar to them in education, social class, race and body weight; this is called assortative effect. The assortative effect based on education was three times stronger than sorting based on genes.

Further research from the LATimes compared 1.7 million single nucleotide polymorphisms and also found that married couples were more genetically similar than random pairs. Even though similarities in genes were found in married couples, it was only one third the magnitude compared to educational similarities found between couples.



Article: http://www.livescience.com/45674-genetic-match-marriage.html

New DNA Sequencing Method

     Genetics has come a long way in the past few years, but a new discovery by Evan Eichler, a professor of genome sciences at the University of Washington, and his colleagues, have discovered many new genetic variants by using new genome sequencing technology. The technique is called single-molecule, real time DNA sequencing (SMRT). Researchers may now be able to identify the genes and genetic mutations in some portions of genome mapping that have eluded scientists. Ultimately, this advancement in genetic mapping may explain the underlying genetic causes of some diseases and conditions.

Example of SMRT sequencing for 5-hmC gene.

     Standard genome sequencing methods are able to map about half of the genome precisely enough to know the genes related to about half of all known heritable diseases. The current way of mapping DNA involves cutting out small snippets of the DNA sequence and overlapping the segments and analyzing the sequence to map the genome. Even though this methods is very accurate and scientists have been able to identify many variation this way, they have been unable to use this method to detect variation that are 50-5,000 bases in length, leaving this part of the genome unknown to everyone.

      SMRT technology allowed Eichler and his colleagues to sequence and read DNA segments that are longer than 5,000 bases, something that cannot be done with standard gene sequencing technology. This technique allows researcher to create a much higher resolution and more well-structured map which leads to being able to detect more structure variation in base pairs. The researchers tested their new approach by doing the genome sequence of a mole. They were able to identify and sequence 26,079 segments that were different from the human genome and 22,000 of these variants had not been reported before. These results show that there is a lot of variation in the human genome that researchers can currently be missing. They were also able to identify 160 genome gaps that were not known before, close 50 gaps, and narrowed 40 others.

      I think that this is a very big advancement in DNA sequencing that will prove be extremely useful in the years to come. Being to to be more specific and uncover hidden genetic variants that can help identify the causes of certain diseases will be extremely helpful to the public, researchers, and doctors. The identification of more genetic variants will help us achieve and even better understanding of the human genome and will have very important, valuable implications for the future of disease diagnosis and prevention.

Original Article :New technology closes many human genome mapping gaps that have long resisted sequencing

Ancient DNA Used to Understand Europeans Today

From the beginning of humans venturing out of Africa to different parts of the world changes in genetic composition have occurred. As their environment changed so did their genetic traits, and those who ended up in Europe were no different. Their skin and hair becoming lighter were the most obvious traits to have changed but many other traits also changed and this can be easily observed from looking at living Europeans today.  However, due to the advanced biotechnology which has now recently been harnessed it is possible to extract DNA from bones of Europeans who lived thousands of years ago.

David Reich, a geneticist at Harvard Medical School and his colleagues have analyzed nine genomes of ancient Europeans, eight of which were hunter-gatherers believed to have been living 8,000 years ago, and one farmer who is believed to have lived 7,000 years ago. Comparing the genomes to Europeans living today the researchers revealed Europeans today have genes from three different populations. The oldest population is the first Europeans who were hunters-gatherers, the second being farmers from the near east who expanded into Europe around 8,500 years ago, and the third, surprisingly, from north Eurasia about 7,000 years ago. Most Europeans today carry all three genes. Most exciting of the study is that now there is a timeline created, describing when and how other areas, such as the east, has influenced Europe.

A 7,700-year-old skeleton of a woman found in Hungary has yielded DNA. Scientists have found that she belonged to a wave of early farmers who moved into Europe from the Near East.

This article was particularly interesting to me because I found the results of the European genetics being influenced by the east interesting. Personally I would have thought that it would be the opposite due to Europe’s huge influence on the entire world early in time. I also am always interested in the techniques which can be used to analyze ancient DNA, although this article did not give much information and detail on the process. 

Article: http://www.nytimes.com/2014/10/30/science/from-ancient-dna-a-clearer-picture-of-europeans-today.html?ref=science&_r=0
Related Article: http://www.cam.ac.uk/research/news/ancient-dna-shows-earliest-european-genomes-weathered-the-ice-age-and-shines-new-light-on

A research team at Washington University in St. Louis, MO lead by Dr. C. Robert Cloninger investigated the genetic influence on schizophrenic disorders.  Approximately 1% of the general population have schizophrenia, but it occurs in around 10% of individuals who have a first-degree relative with this disorder.

Previous research like a study done at Cardiff University of Medicine focused on identifying new genes linked to Schizophrenia. However, in this study, Dr. Cloninger and his team choose to take a more collaborative approach by considering the interaction of several genes.  "[Genes] function in concert much like an orchestra, and to understand how they're working, you have to know not just who the members of the orchestra and how they interact."

In this study the genomes of 4,2000 people with schizophrenia and 3,800 without the disorder were analyzed. The team examined nearly 700,000 areas of the genome searching for  single nucleotidepolymorpism (SNP). SNP occurs when there is a variation within a single unit of DNA.

                                         WHATS THE IMPORTANCE? 

The study found that genes that are linked to schizophrenia individually have inconsistent associations with the disorder, however; when working together as clusters, they created a risk of 70-100% for the development of the disorder.

In identifying the genetic variations and symptoms they produce, it may be possible to select more efficient treatments for specific pathways that are responsible for the disorder. Dr. Cloninger and his research team's approach appears to be an efficient and innovative way to examine the source of this disease. Considering a larger scale, the application of this research can expand and be groundbreaking in regards to understanding other common complex health issues such as heart disease, diabetes and hypertension. 

Article: http://www.medicalnewstoday.com/articles/282539.php 

Kids who don't cry

Is there honestly such thing as a little kid who doesn't cry? The Human Genome Project has begun to identify new genetic mutations, and it is getting very easy and cheap. When identifying a new genetic disorder, studying multiple patients with the same gene mutations is necessary. When new genetic mutations are discovered they are usually found by accident, usually when a mystery illness is being researched. This happened in a specific case dealing with a little girl named Grace.....

http://www.cnn.com/2014/03/20/health/ngly1-genetic-disorder/ 

... where a family was dealing with a problem with their daughter. They weren't sure what was going on with their girl, as she was dealing with strange symptoms for some time. She was refusing to eat, eyes were hollowed, and just wasn't acting herself. 

This family, was distraught when their baby girl was acting strange day in and day out and they wouldn't rest until they found an answer. They brought her to a doctor and the testing began. They really had no idea what was wrong with her from the start, until a little research was done. They looked into Grace's genes and realized that Grace's mutations of the NGLY1 gene were the destructive kind. The doctor wasn't sure what to think so he searched other work done with this gene and possible problems. The search was really going no where until the doctor found a case very similar to Grace's. The work done hadn't been exactly finished due to this research group had no other work to compare theirs too. So, naturally when Grace's case arose, the connection between the two lit the way. The biggest connection, at first, between the two cases was that both children had the inability to cry. When the doctors figured out the connection between the two it was a "Eureka" moment. The mutation of this gene was then able to be connected to 12 other cases and the mutation is now being researched further.

Genetics Breakthrough Enables Scientists to Edit Any Part of Human Genome

 A new and precise engineering technique has been brought to light that holds the potential to act as a treatment for cancer, HIV, and inherited genetic disorders. The technique is called Crispr and it allows for detailed alterations to any of the 23 pairs of human chromosomes with minimal to practically no risk of unintended mutations. It works by using RNA guide molecules that are programmed with any unique DNA sequence wanted from the human genome. This piece of RNA is attached to a cutting enzyme that will cut into the DNA double helix, attached the RNA guide molecule, and the unwanted DNA is removed. Crispr isn't just for human gene therapy. It can also be used in agriculture and livestock, though most experts are more impressed with the potential Crispr has with human beings. For example, using this technique, it could be possible to eliminate Down syndrome.

This technique will undoubtedly be attacked by people who do not believe in modifying with the way nature intended. Most likely the arguments that will arise will be that if a person is born with some sort of genetic complication, that they were meant to have it. They will dismiss the fact that Crispr could make a potentially painful and short life into a painless long life. It is of this blogger's opinion that these people might not fully understand that nature is all about testing and changing. Sometimes those tests fail and end up being something that kills instead of aids, so what's the harm in making nature's failures go away? As long as we respect nature and don't go power crazy, Crispr has the potential for greatness.

Article: http://www.foxnews.com/science/2013/11/07/report-genetics-breakthrough-enables-scientists-to-edit-any-part-human-genome/

Further Reading on Crispr: http://www.independent.co.uk/news/science/exclusive-jawdropping-breakthrough-hailed-as-landmark-in-fight-against-hereditary-diseases-as-crispr-technique-heralds-genetic-revolution-8925295.html

Recreating the History of Life Through the Genome

    The Spanish National Cancer Research Center has begun a new project to map the human genome as use it as a timeline for understanding evolutionary processes. They hypothesize that "old" genes replecate first, while "newer" genes replicate last. In this way, they expect to be able to discern a relative mutation timeline based on the order of gene replication within the genome. The Research Center also posits that the older genes are safer from mutation because they are deeper within the genome, a product of their order in replication. Conversely, "new" genes are more likely to mutate (because they are towards the end of the genome), thus providing speciation within affecting the traits that are essential to life.

     The hypotheses presented by the research center make a great deal of sense to me, and would go a long way towards explaining evolution and its relationship with genetics. My limited knowlege of the two subjects lead me unable to discern the credulity of their statements, but from my point of view they appear to be at least possible (if not extremely likely). I'd be interested in further evidence for these claims.

http://www.sciencedaily.com/releases/2013/11/131119101044.htm
http://www.technologyreview.com/news/521626/genomics-technology-races-to-save-newborns/

Report claims that scientists are able to edit any part of the human genome

In Great Britain a new technique known as Crispr, enables scientists to engineer parts of the genome with extreme precision. This type of precision holds the key to new treatments towards cancer, HIV, and inherited genetic disorders. Crispr operates by enabling the most detailed and specific possible alteration to any part of DNA of the 23 pairs of human chromosomes without introducing unintended mutation or flaws. 2006 Nobel Prize winner Craig Mello describes Crispr as, “incredibly powerful and it has many applications, from agriculture to potential gene therapy in humans.” Tofigure out the alterations that could take place Crispr works by using an RNA guide molecule that can be programmed to match any unique DNA sequence in the human genome. The molecule is attached to a special enzyme that cut both strands of the DNA double helix. The copied DNA then is inserted into the double helix and defective DNA is deleted. Some scientists are arguing that the technique could be used to eliminate certain genetic diseases like Down Syndrome and Huntington’s Disease by altering the DNA of an embryo before implanting it in the mother’s womb.

http://www.foxnews.com/science/2013/11/07/report-genetics-breakthrough-enables-scientists-to-edit-any-part-human-genome/

http://guardianlv.com/2013/11/genetic-crispr-radical-game-changer-against-incurable-conditions/

Famous "HeLa" Human Cell Line Gets Its DNA Sequenced

HeLa cells, immortal cells taken from the deadly cervical tumor form Henrietta Lacks, has been sequenced by researchers. The cells were established in 1951 after Lacks died of her cancer. These cells were the first cells to survive in the lab after more than a couple of days. The cells have contributed to much research including to the development of the polio vaccine as well as more than 60,000 research papers. These cells have been replicated in many labs around the world for six decades.

The genome of the HeLa cell line has been sequenced by a team at the European Molecular Biology Laboratory in Heidelberg, Germany lead by geneticist Lars Steinmetz. His team confirmed that HeLa cells contain one extra version of most chromosomes, with up to five copies of some. It was also found that large segments of chromosome 11 and many other chromosomes had massive rearrangements, which could be contributed to the cervical tumor. With the genome now sequenced and showing to be full of errors Steinmetz brings of the question of its continued use as models for human cell biology. Having been replicated for so long the cell has evolved, the cell has accumulated errors that are not present in the original tumor DNA.



http://www.scientificamerican.com/article.cfm?id=famous-hela-human-cell-line-gets-its-dna-sequenced&print=true