Backed by the Obama administration, the Brain Activity Map (BAM) project will span a decade with the goal of determining how brain cells collectively process information.

The U.S. already has one brain-mapping initiative under way, the Human Connectome Project. Launched in 2009, the goal of the Human Connectome Project is to construct a map of the complete structural and functional neural connections in vivo within and across individuals. The BAM project would go beyond an organizational and operational map and chart brain activity at the level of individual neurons.

“We propose to record every action potential from every neuron within a circuit,” write scientists, laying the groundwork for the BAM project in the journal Neuron last year [1]. To achieve this goal the scientists will need to study the connections between thousands to millions of cells while they are still alive — not something easy to accomplish.

With approximately 100 billion neurons, the brain is by far the most complex organ known. Although there is a good deal of knowledge regarding whole-brain activity patterns and single-cell structure and function, how “circuits” or “networks” of brain cells work together in both normal and disease states remains mostly a mystery. Scientists have not yet found a way to record the activity of more than a small number of neurons at once, non-invasively in living tissue.

Discussed in the March 2013 issue of the journal Science, the BAM research program is primarily technology-building and will develop three types of tools: those that can help simultaneously image or record the individual activity of neurons within a network; those that can control the activity of every neuron individually; and those that can store, manage, analyze, model and share large-scale imaging and physiology data [2].

Researchers suggest that these tools might include molecule-size wireless microcircuits that could be deployed, untethered, in living brains to monitor neuronal activity. DNA molecules could be synthesized to serve as a “ticker-tape” record.

The hope is that the BAM project will be an open, international collaboration of scientists, engineers and theoreticians throughout academia and industry. The plan is to start with small-brained invertebrates such as the worm, fly or leech, and then move up in brain complexity, ultimately working in humans. The authors write that within five years, it should be possible to monitor and control tens of thousands of neurons, and within 15 years, 1 million neurons — with “markedly reduced invasiveness”.

Although it is not yet clear how much federal money will actually be approved for the project, it won’t be cheap — at least $300 million a year, or $3 billion over a decade. However, during his 2013 State of the Union address, President Obama highlighted brain research as a leading candidate for government funding and alluded to the positive effect a project like BAM could have on the economy. He likened the BAM project to the Human Genome Project, which cost taxpayers $3.8 billion, but had a significant return on investment, returning $140 for every dollar invested.

Ray Suarez from PBS NewsHour recently interviewed Dr. Francis Collins, Director of the National Institutes of Health, which would coordinate much of the BAW project. You can watch the interview below.

The organizations slated to participate in the planning and funding of the BAM project include the Office of Science and Technology Policy, the National Institutes of Health, the Defense Advanced Research Projects Agency (DARPA), the National Science Foundation, and private foundations, such as the Howard Hughes Medical Institute.

References

1. Alivisatos et al. The brain activity map project and the challenge of functional connectomics. Neuron. 2012 Jun 21;74(6):970-4. doi: 10.1016/j.neuron.2012.06.006.
   View abstract
2. Alivisatos et al. The Brain Activity Map. Science. 2013 Mar 7. [Epub ahead of print]
   View abstract

Working with material from rat brains, the researchers found some expanses of DNA contained the information that generate biologically active molecules. The levels of these molecules rose and fell, in synchrony with 24-hour cycles of light and darkness. Activity of some of the molecules peaked at night and diminished during the day, while the remainder peaked during the day and diminished during the night.

The material came from the brain structure known as the pineal gland. Located in the center of the human brain, the pineal gland helps regulate the body’s responses to day and night cycles, the researchers explained. In the evenings and at night, the pineal gland increases production of melatonin, a hormone that synchronizes the body’s rhythms with the cycle of light and dark. In many species, the pineal gland also plays a role in seasonally associated behaviors, such as hibernation and mating, as well as in sexual maturation.

The biologically active material arising from the pineal gland DNA is called long noncoding RNA (lncRNA). The lncRNA is distinct from the better-known messenger RNA (mRNA), which serves as a kind of template to translate the information contained in DNA for the manufacturing of proteins. The lncRNAs appear instead to be involved in activating, blocking or altering the activity of genes or influencing the function of the proteins, or acting as scaffolds for the organization of complexes of proteins. The researchers’ use of next-generation sequencing methods detected the lncRNA activity in addition to the mRNA they originally targeted, which helped them in making their discovery.

Senior author David Klein, Ph.D., head of the Section on Neuroendocrinology at the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), where much of the research was conducted, said:

These lncRNAs come from areas of the genome that we thought were quiet. But current research in the field makes it unequivocally clear that the information-carrying capacity of the genome is a lot greater than we realized previously.

The study was a collaboration between Dr. Klein and NIH colleagues at the NICHD; the National Human Genome Research Institute (NHGRI); the NIH Intramural Sequencing Center, administered by NHGRI and the Center for Information Technology. In addition, researchers from King’s College London; the University of Copenhagen, in Denmark; the Genomatix Software company, in Munich contributed to the study.

To conduct their analysis, the researchers examined RNA from the pineal glands of rats exposed to cycles of 14 hours of light and 10 hours of darkness. The researchers identified 112 lncRNAs with 24 hour cycles. For nearly 60 percent of these lncRNAs, the rats’ DNA produced twice as many lncRNA molecules at night as during the day. In addition, nearly 90 percent of the lncRNAs were produced in significantly greater quantities in the pineal gland than in other tissues of the body, most of which did not have detectable levels of these lncRNAs.

The researchers also disrupted the rats’ regular day-night light cycle by turning on a light during a typical dark period. Within 30 minutes of the light going on, most of the lncRNAs decreased by half.

The role of the pineal gland lncRNAs is unclear; however, they have circadian patterns of activity. Dr. Klein previously documented hundreds of genes in the pineal gland with consistent day-night cycles of activity [2].

Dr. Klein said:

The lncRNAs show such strong activity, they obviously have something to tell us about the biology of daily body rhythms. We are only beginning to understand how the pineal gland helps maintain the body’s 24 hour rhythms.

Source: NIH News

References

1. Coon et al. Circadian changes in long noncoding RNAs in the pineal gland. Proc Natl Acad Sci U S A. 2012 Aug 14;109(33):13319-24. Epub 2012 Aug 3.
   View abstract
2. Klein et al. Night/day changes in pineal expression of >600 genes: central role of adrenergic/cAMP signaling. J Biol Chem. 2009 Mar 20;284(12):7606-22. Epub 2008 Dec 22.
   View abstract

Image credit: DNA structure via Shutterstock

A recent article published in Clinical and Experimental Allergy notes that epigenetic factors can help explain the significant increase in food allergy prevalence in developed nations [1]. The mechanism by which the rate of food allergy has increased so rapidly has been puzzling to researchers; it’s happened too quickly to be accounted for purely in genetic terms. However, food allergies appear to have a strong genetic component, since they run in families and co-occur with a number of other related disorders, including eczema and asthma. In fact, it appears that there are two influences that increase the likelihood of an individual having a food allergy: genetic predisposition (family members with allergies), and a “modern lifestyle” [2].

How does the environment influence genetics? Simply put, an individual’s characteristics are encoded in genetic material — DNA — but not everything encoded in DNA is actually expressed.

Some genes remain “silent,” and researchers are increasingly realizing that environmental factors may cause the expression of genes that, in the absence of that environmental trigger, would have remained inactive. In a very real sense, the environment can turn genes on and off, changing physical characteristics, influencing health, and affecting behavior. Furthermore, it seems that the prenatal period — the time during which a fetus is developing in utero — is particularly important with regard to epigenetic influences [3].

While the scientific understanding of food allergies (and of epigenetics in general) is still in its infancy, it appears that researchers will increasingly focus on the effects of environmental triggers on gene sequences that predispose individuals to develop allergies. In so doing, it might someday be possible for those individuals from families with high risk of allergies to avoid the environmental triggers that turn allergy-related genes on in the first place.

References

1. Tan et al. The role of genetics and environment in the rise of childhood food allergy. Clin Exp Allergy. 2012 Jan;42(1):20-9. doi: 10.1111/j.1365-2222.2011.03823.x. Epub 2011 Jul 19.
   View abstract
2. Jackson, M. Allergy: the making of a modern plague. Clin Exp Allergy. 2001 Nov;31(11):1665-71.
   View abstract
3. Bird, A. Perceptions of epigenetics. Nature. 2007 May 24;447(7143):396-8.
   View abstract

Folic acid is one of the many vitamins pregnant women need to take in order to ensure normal fetal development. In fact, it may be the most critical prenatal supplement, both because many women don’t consume enough folic acid in food, and because deficiencies can lead to serious developmental problems, including neural tube defect, which is associated with spina bifida.

Researchers from the Norwegian Institute of Public Health, Oslo, and colleagues carried out a study to investigate whether a woman’s use of folic acid supplements was associated with a reduced risk of severe language delay among offspring at 3 years of age. The scientists tracked the use of folic acid supplements and other supplements in nearly 40,000 expectant women and followed up with them and their children at 3 years of age. They found that children of women who took other supplements — but no folic acid — were significantly more likely than children of women who took folic acid alone, or folic acid in combination with other supplements, to have severe language delay.

Folic acid is one of the B vitamins; specifically, it’s vitamin B9. In reality, there are several different forms of the vitamin, where folic acid is the form most commonly found in supplements. There are many different folic acid derivative chemicals, collectively called “folates,” which are found in foods and which are the forms used by the human body. Because they’re less stable than folic acid, however, they’re generally not used to produce supplements. Still the human body can use the folic acid in supplements to make physiologically active folates. Chemically-speaking, folates are coenzymes, and are critical participants in reactions in the body that involve amino acids and nucleic acids (biological molecules essential for life that include DNA and RNA).

While folic acid supplementation is recommended throughout pregnancy, it’s actually most critical in a pregnancy’s earliest days. The neural tube, a structure that eventually becomes the brain and spinal cord, develops during the third week post-conception (the fifth week of pregnancy). Because this crucial developmental step takes place so early, many women are not yet aware that they’re pregnant. Further, low folic acid status can be subclinical (that is to say, it’s possible to be somewhat deficient in folic acid without realizing it). Consequently, the American Academy of Pediatrics recommends that all women of childbearing years who could potentially become pregnant take 4 mg of folic acid daily [2].

While the importance of folic acid supplementation pre-conception and during early pregnancy has been known for some time, the Norwegian study is the first to scientifically evaluate whether folic acid supplementation continues to have an impact on neural development beyond the formation of the neural tube. The large size of the study and great significance of the results (the difference in outcomes between the groups was large) indicate that folic acid likely continues to play important developmental roles beyond the end of the fifth week of pregnancy. The researchers did not attempt to determine how long women needed to continue taking folic acid supplements in order for their children to reap the benefits; the women included in the “folic acid supplementation” group took folic acid supplements from at least four weeks prior to conception through at least eight weeks after conception, but they were not told to stop taking supplements after that time, and many may have continued to do so. As such, it’s wise to continue folic acid supplementation throughout pregnancy in order to maximize its potential benefits to fetal development.

References

1. Roth et al. Folic acid supplements in pregnancy and severe language delay in children. JAMA. 2011 Oct 12;306(14):1566-73.
   View abstract
2. Folic acid for the prevention of neural tube defects. American Academy of Pediatrics. Committee on Genetics. Pediatrics. 1999 Aug;104(2 Pt 1):325-7.
   View abstract

“The pilot studies of the 1000 Genomes Project laid a critical foundation for studying human genetic variation,” said Richard Durbin, Ph.D., of the Wellcome Trust Sanger Institute and co-chair of the consortium. “These proof-of-principle studies are enabling consortium scientists to create a comprehensive, publicly available map of genetic variation that will ultimately collect sequence from 2,500 people from multiple populations worldwide and underpin future genetics research.”

Genetic variation between people refers to differences in the order of the chemical units — called bases — that make up DNA in the human genome. These differences can be as small as a single base being replaced by a different one “” which is called a single nucleotide polymorphism (abbreviated SNP) — or is as large as whole sections of a chromosome being duplicated or relocated to another place in the genome. Some of these variations are common in the population and some are rare. By comparing many individuals to one another and by comparing one population to other populations, researchers can create a map of all types of genetic variation.

The 1000 Genomes Project’s aim is to provide a comprehensive public resource that supports researchers aiming to study all types of genetic variation that might cause human disease. The project’s approach goes beyond previous efforts in capturing and integrating data on all types of variation, and by studying samples from numerous human populations with informed consent allowing free data release without restriction on use. Already, these data have been used in studies of the genetic basis for disease.

“By making data from the project freely available to the research community, it is already impacting research for both rare and common diseases,” said David Altshuler, M.D., Ph.D., deputy director of the Broad Institute of Harvard and MIT, and a co-chair of the project. “Biotech companies have developed genotyping products to test common variants from the project for a role in disease. Every published study using next-generation sequencing to find rare disease mutations, and those in cancer, used project data to filter out variants that might obscure their results.”

The project has studied populations with European, West African and East Asian ancestry. Using the newest technologies for sequencing DNA, the project’s nine centers sequenced the whole genome of 179 people and the protein-coding genes of 697 people. Each region was sequenced several times, so that more than 4.5 terabases (4.5 million million base letters) of DNA sequence were collected. A consortium involving academic centers on multiple continents and technology companies that developed the sequencing equipment carried out the work.

To process these data required many technical and computational innovations, including standardized ways to organize, store, analyze and share DNA sequencing data. Launched in 2008, the 1000 Genomes Project started with three pilot projects to develop, evaluate and compare strategies for producing a catalogue of genetic variations. Funded through numerous mechanisms by foundations and national governments, the 1000 Genomes Project will cost some $120 million over five years, ending in 2012.

When the work began, sequencing was very expensive, so the project began with two approaches aimed at increasing efficiency: One strategy — called “low pass” — combines partial data from many people; the second only focused on the part of the genome that encodes protein-coding genes. By comparing these strategies to “gold standard” data produced at great completeness and accuracy, the project was able to show that both the alternative approaches work well and have complementary strengths. Researchers will use both strategies in the full-scale project because, although sequencing costs have decreased, it is still relatively expensive.

“We have shown for the first time that a new approach to sequencing — low coverage of many samples — works efficiently and well,” said Gil McVean, Ph.D., professor of statistical genetics at the University of Oxford. “This proof of principle is now being applied not only in the 1000 Genomes Project, but in disease research, as well.”

The resulting map of human genetic variation includes about 15 million SNPs, 1 million short insertion/deletion changes, and more than 20,000 structural variations. Many of the genetic variants had previously been identified, but more than half were new. The project’s database contains more than 95 percent of the currently measurable variants found in any individual, and continuing work will eventually identify more than 99 percent of human variants.

Richard Gibbs, Ph.D., director of the Human Genome Sequencing Center at the Baylor College of Medicine (one of the projects sequencing centers) said: “What really excites me about this project is the focus on identifying variants in the protein-coding genes that have functional consequences. These will be extremely useful for studies of disease and evolution.”

The improved map produced some surprises. For example, the researchers discovered that on average, each person carries between 250 and 300 genetic changes that would cause a gene to stop working normally, and that each person also carried between 50 and 100 genetic variations that had previously been associated with an inherited disease. No human carries a perfect set of genes. Fortunately, because each person carries at least two copies of every gene, individuals likely remain healthy, even while carrying these defective genes, if the second copy works normally.

In addition to looking at variants that are shared among many people, the researchers also investigated in detail the genomes of six people: two mother-father-daughter nuclear families. By finding new variants present in the daughter but not the parents, the team was able to observe the precise rate of mutations in humans, showing that each person has approximately 60 new mutations that are not in either parent.

With the completion of the pilot phase, the 1000 Genomes Project has moved into full-scale studies in which 2,500 samples from 27 populations will be studied over the next two years. Data from the pilot studies and the full-scale project are freely available on the project website, http://www.1000genomes.org/.

Researchers studying specific illnesses, such as heart disease or cancer, use maps of genetic variation to help them identify genetic changes that may contribute to the illnesses. Over the last five years, the first generation of such studies (called genome-wide association studies or GWAS) have been based on an earlier map of genetic variation called the HapMap. Built using older technology, HapMap lacks the completeness and detail of the 1000 Genomes Project.

“The 1000 Genomes Project map fills in the gaps between the HapMap landmarks, helping researchers identify all candidate genes in a region associated with a disease,” said Lisa Brooks, Ph.D., program director for the Genetic Variation Program at the National Human Genome Research Institute, a part of the National Institutes of Health. “Once a disease-associated region of the genome is identified, experimental studies must be done to identify which variants, genes and regulatory elements cause the increased disease risk. With the new map, researchers can just look up all the candidate genes and almost all of the variants in the database, saving them many steps in finding the causes.”

Organizations that committed major support to the project include: 454 Life Sciences, a Roche company, Branford, Conn.; Life Technologies Corporation, Carlsbad, Calif.; BGI-Shenzhen, Shenzhen, China; Illumina Inc., San Diego; the Max Planck Institute for Molecular Genetics, Berlin, Germany; the Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK; and the National Human Genome Research Institute, Bethesda, Md., which supports the work being done by Baylor College of Medicine, Houston, Texas; the Broad Institute, Cambridge, Mass.; and Washington University, St. Louis, Missouri. Researchers at many other institutions are also participating in the project including groups in Barbados, Canada, China, Colombia, Finland, the Gambia, India, Malawi, Pakistan, Peru, Puerto Rico, Spain, the UK, the US, and Vietnam. Additional information about the project, including a list of all participants and organizations, can be found at http://www.1000genomes.org/.

Source: NIH News

Two women, Elizabeth H. Blackburn, age 61, at the University of California in San Francisco, and Carol W. Greider, age 48, at Johns Hopkins University School of Medicine in Baltimore along with one man, Jack W. Szostak, age 57, at Harvard Medical School, will share the $1.4 million prize.

Telomeres are regions of repeating DNA sequence at the ends of chromosomes (picture the aglets, or plastic sleeves, at the ends of a shoelace). These unique sequences serve to protect the chromosomes from being degraded as cells divide. The enzyme that forms telomeres is called telomerase. If the telomeres are shortened, cells age. In contrast, if telomerase activity is high, telomere length is maintained and cellular senescence (meaning the processes of deterioration) is delayed.

Increased telomerase activity is observed in cancer cells. Modestly reduced telomerase activity is implicated in bone marrow failure and pulmonary fibrosis [1]. Accelerated shortening of telomeres in peripheral blood lymphocytes, including T cells, has been observed in a number of diseases, including Down syndrome, rheumatoid arthritis and cardiovascular disease [2-4]. Research also suggests that telomere shortening occurs in mood disorders [5].

A brief history of telomere and telomerase research

Elizabeth Blackburn was studying a unicellular organism called Tetrahymena in the early 1980s and observed that a DNA sequence was repeated several times at the ends of chromosomes. At the same time, Jack Szostak had observed that a linear DNA molecule, a type of minichromosome, was rapidly degraded when introduced in yeast cells. Blackburn and Szostak collaborated to couple the repeated Tetrahymena DNA sequence to the minichromosome. Surprisingly, the repeated DNA sequence — now recognized as a telomere — protected the minichromosome from degradation [6]. Szostak went on to identify mutations in yeast that led to a progressive decrease in telomere length and increased frequency of chromosome loss [7]. In subsequent years with further research, it became clear that telomeres, with its characteristic repeated DNA sequence, is present in most plants and animals.

Carol Greider was a graduate student of Blackburn, who in 1984 provided evidence for an enzyme that could form telomere DNA. Greider and Blackburn purified the enzyme and called it telomerase. They showed that telomerase extends telomere DNA necessary for the replication of chromosome ends [8-9].

NIH Director Francis S. Collins, M.D., Ph.D., said [10]:

The question of how cellular aging relates to abnormal cell division, such as cancer, and the aging of organisms continues to be the focus of rigorous study, thanks to the insights of Drs. Greider, Blackburn and Szostak. These NIH grantees’ discoveries offer a classic example of how basic science research driven by investigators’ curiosity can illuminate our understanding of health and disease.

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References

1. Lansdorp PM. Telomeres and disease. EMBO J. 2009 Sep 2;28(17):2532-40. Epub 2009 Jul 23.
   View abstract
2. Vaziri et al. Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes. Am J Hum Genet. 1993 Apr;52(4):661-7.
   View abstract
3. Koetz et al. T cell homeostasis in patients with rheumatoid arthritis. Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):9203-8.
   View abstract
4. Fuster and Andres. Telomere biology and cardiovascular disease. Circ Res. 2006 Nov 24;99(11):1167-80.
   View abstract
5. Simon et al. Telomere shortening and mood disorders: preliminary support for a chronic stress model of accelerated aging. Biol Psychiatry. 2006 Sep 1;60(5):432-5. Epub 2006 Apr 11.
   View abstract
6. Szostak and Blackburn. Cloning yeast telomeres on linear plasmid vectors. Cell. 1982 May;29(1):245-55.
   View abstract
7. Lundblad and Szostak. A mutant with a defect in telomere elongation leads to senescence in yeast. Cell. 1989 May 19;57(4):633-43.
   View abstract
8. Greider and Blackburn. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell. 1985 Dec;43(2 Pt 1):405-13.
   View abstract
9. Greider and Blackburn. The telomere terminal transferase of Tetrahymena is a ribonucleoprotein enzyme with two kinds of primer specificity. Cell. 1987 Dec 24;51(6):887-98.
   View abstract
10. NIH Grantees Win 2009 Nobel Prize in Physiology or Medicine for Telomere Research. NIH News. 2009 Oct 6.

logo credit: Ricardo @ My Biotech Life

Google Health launched publicly this week and to recognize the event, the last section of the carnival is devoted to articles specifically about the service. Google, financial backer of 23andMe, also funds the Personal Genome Project, which plans to unlock the secrets of common diseases by decoding the DNA of 100,000 people in the world’s biggest gene sequencing project [1]. With the vast number of genetic data points collected for each genome sequenced, a digital system for the movement and storage of personal health information is critical for the widespread use of individualized healthcare. Google’s entrance into the online personal health records market may thus help to accelerate the era of personalized medicine.

With these thoughts in mind, let’s get to this month’s edition of the Genie.

Genes and gene-related diseases

Dr Shock MD PhD

Rates of depression and other psychiatric disorders are higher in people who have two copies of a genetic variant of the serotonin transporter gene as a function of exposure to increasing levels of stressful life events. A recent study examined the biological reactivity to stress in people with two copies of the allele [3]. Dr. Shock asks How Can Genes and Stress Cause Depression?

Genetics & Health

Researchers in Canada recently tested the hypothesis that DNA methylation plays a role in alterations in gene expression in the suicide brain [4]. Elaine Warburton describes Suicide – Genetic Changes in Brain as a Result of Childhood Abuse.

Think Gene

Schwann cells insulate nerves in the peripheral nervous system and can dedifferentiate with injury to accelerate healing. A recent study demonstrates that c-Jun is an important regulator of this plasticity [5]. Josh Hill reports that c-Jun is Turning Back the Clock for Schwann Cells.

Eye on DNA

Hsien-Hsien considers the possibility of 23andMe showing personalized ads for personalized medicine, and hopes that the Parkinson’s Institute and Clinical Center will have compliant study participants when 23andMe Collaborates on Study of Parkinson’s Disease Genetics.

Retail Genomics

Simon Lin also writes about the collaboration between 23andMe and the Parkinson’s Institute. 23andme is Shaking up Clinical Research, and Simon’s happy to see the combination of consumer genomics and clinical trials.

The Skeptical Alchemist

Mice laking the glucose transporter gene Glut2 fail to control their food intake, suggesting a role for glucose sensing in the brain. Steppen Wolf reviews a study in humans showing that individuals with a genetic variant of the same glucose transporter, GLUT2, have a higher daily intake of sugar [6]. Now there’s Finally an Excuse for My Sweet Tooth!

The Spittoon

A recent genome-wide association study in Asians found an association between a SNP of the gene PSCA and an increased risk of diffuse-type gastric cancer [7]. Erin Cline reviews the study in SNPWatch: Researchers Find SNP Associated with Diffuse-type Gastric Cancer.

Genetics

Nimravid’s Weblog

The foundation of comparative genomics is that genes that are shared between closely related species have similar function and cause similar phenotypes when deleted from the genome. Nimravid reviews a systematic examination of this hypothesis [8]. Are You a Human or a Mouse?

Greg Laden’s Blog

A method for increasing the power of genetic studies in canines is to sample dogs of the same breed but from different geographic areas. A recent study assessed the genetic variation among dogs of the same breed collected from different geographic regions [9]. Greg Laden reviews the study and describes genetic variation, disease-connected alleles and dogs in his article Evolutionary Genetics of Canine Population Structure.

Adaptive Complexity

A review of genome-wide association studies highlights the knowledge gained and challenges that remain as researchers work to identify sequence variation and disease predisposition [10]. Adaptive Complexity covers The First Report Card for Genome Wide Association Studies.

PredictER Blog

Jere Odell writes about a genetic counselor’s response to a Nature article reporting the genomic DNA sequence of James D. Watson [11]. Dr Watson’s Genetic Counselor: Witty or Insulting?

Sciencebase

David Bradley discusses Genetic Manipulation and asks, “Do the GM pros outweigh the cons?”

Genomics

Genomicron

T Ryan Gregory explores the multiple meanings of the term genome, clarifying “what is a genome?” and “Whose Genome was sequenced?”

Gene Sherpas: Personalized Medicine and You

Timing is everything. Steve Murphy highlights two major impacts on the future of Genomic Medicine last week when he writes about Timing, GINA is Law and the Future of Genomic Medicine.

Giovanna Di Sauro

A recent study used transgenesis to evaluate the function of sequences obtained from an extinct species in transgenic mice [12]. Giovanna Di Sauro tells us about Jurassic Park in the real world with her article Tasmanian Park: Extinct Mammalian DNA Back to Life.

Next Generation Sequencing

The NGS blog reports that the Genome Reference Consortium Launched. The consortium’s goal is to correct the small number of regions in the reference that are misrepresented, to close as many gaps as possible and to produce alternative assemblies of structurally variant loci.

Personalized Genetics

Scienceroll

Berci Mesko discusses the recent improvements of individualized medicine in his article Personalized Genetics: Privacy and the Virtual Gene.

PredictER Blog

How would personalized genetic information change the perceptions of risk and behaviors of people making retirement plans? Jere Odell ponders Retirement and Risk: Betting on Your Genes?

Think Gene

Personalized genetic services test for SNPs, DNA sequence variations that occur when a single nucleotide — A, T, C or G — in the genome is changed, producing different alleles. Most services test between 500,000 and 1,000,000 SNPs, yet interpret less that 100 traits. Kevin Fischer demonstrates how to get more information about your genome. Tell me Everything: How To Use SNPedia for 23andMe and deCODEme.

The Genetic Genealogist

How reproducible are the results of genome scanning services? Blaine Bettinger evaluates the Accuracy of Large-Scale Genome Scanning Services. He follows the article up by assessing the Reproducibility of SNP Testing.

DNA Direct Talk

After speaking about competition in the lab testing space at the Executive War College on Laboratory and Pathology Management, Trisha Brown reports that It’s Not Just the Test, It’s the Service.

Genetic Future

Daniel reflects on a panel discussion on direct-to-consumer genetic testing of 23andMe, deCODEme and Navigenics at Cold Spring Harbor.

Genome Alberta Education

In an on-going blog series that serves as a ‘consumer guide to personal genotyping’, Mike Spear describes Genomics at Quinpool, recounting some comments and questions from the Youth Forum on Personal Genomics where students and a panel of experts looked at his personal genome test report and SNP file.

Google Health

business | bytes | genes | molecules

Deepak Singh gives the service a quick synopsis in his article Your Personal Health: Google Health is Live.

TechCrunch

Techcrunch gives Google Health A Quick Hands-On Look.

ReadWriteWeb

Richard MacManus reviews the limitations of Google Health in his article Google Health Launches – Cautious, Non-Innovative Entry into Health 2.0.

e-patients.net

As Google Releases Google Health, John Grohol expresses concern that an individual’s Google Health record may be an ideal way for other companies to market to them based on their specific health concerns.

Pimm – Partial immortalization

Attila Csordas gives us some background of Google Health’s product manager, asking that we Meet Dr. Google Health: Roni Zeiger, right from Stanford!

Scienceroll

Berci Meskó hopes he will never get pharma ads or spams from doctors based on his health profile when he announces Google Health: The First Steps.

Conclusion

That concludes the 32nd edition of Gene Genie. My thanks to everyone who submitted an article. You can find more information about the carnival as well as the hosting schedule and past editions at the Gene Genie Website. The next edition will be hosted at Neurophilosophy on June 8th.

References

1. Google Backs Harvard Scientist’s 100,000-Genome Quest (Update2). Bloomberg.com 2008 Feb 29.
2. Pearson H. Genetics: what is a gene? Nature. 2006 May 25;441(7092):398-401.
   View abstract
3. Gotlib et al. HPA axis reactivity: a mechanism underlying the associations among 5-HTTLPR, stress, and depression. Biol Psychiatry. 2008 May 1;63(9):847-51. Epub 2007 Nov 19.
   View abstract
4. McGowan et al. Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain. PLoS ONE. 2008 May 7;3(5):e2085.
   View abstract
5. Parkinson et al. c-Jun is a negative regulator of myelination. J Cell Biol. 2008 May 19;181(4):625-37.
   View abstract
6. Eny et al. Genetic variant in the glucose transporter type 2 is associated with higher intakes of sugars in two distinct populations. Physiol Genomics. 2008 May 13;33(3):355-60. Epub 2008 Mar 18.
   View abstract
7. The Study Group of Millennium Genome Project for Cancer. Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer. Nat Genet. 2008 May 18. [Epub ahead of print]
   View abstract
8. Liao and Zhang. Null mutations in human and mouse orthologs frequently result in different phenotypes. Proc Natl Acad Sci U S A. 2008 May 13;105(19):6987-92. Epub 2008 May 5.
   View abstract
9. Quignon et al. Canine population structure: assessment and impact of intra-breed stratification on SNP-based association studies. PLoS ONE. 2007 Dec 19;2(12):e1324.
   View abstract
10. McCarthy et al. Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nat Rev Genet. 2008 May;9(5):356-69.
    View abstract
11. Roche MI. A case of genetic counselling for Dr Watson. Nature. 2008 May 15;453(7193):281.
    View abstract
12. Pask et al. Resurrection of DNA Function In Vivo from an Extinct Genome. PLoS ONE. 2008 May 21;3(5):e2240.
    View abstract

The all employ a widely used molecular technique called polymerase chain reaction or PCR.

The idea was conceived by Kary Mullis in the early 1980s and was first described, albeit briefly, in an article investigating the mutation that causes sickle cell anemia [1]. The details of the method and its uses were discussed in greater detail over the next two years [2-3]. PCR revolutionized molecular genetics by allowing rapid duplication and analysis of DNA.

The PCR method

PCR is used to amplify a specific region of DNA in order to produce a large number of nearly identical copies. The method uses a heatstable DNA replication enzyme called a DNA polymerase, the four deoxynucleotide building blocks of DNA and two small single-stranded DNA segments called primers, which flank the “target” region of DNA to be amplified and are complementary to each strand (meaning the matching strand to which its bases pair).

There are 3 basic steps in PCR that are carried out at different temperatures to create conditions optimal for:

1. DNA denaturation (meaning to separate the double-stranded DNA into single strands).
2. Primer binding or hybridization to each of the single strands of DNA at either the beginning or the end of the target sequence, depending upon the single-strand of DNA. Hybridization combines complementary, single-stranded DNA into a single molecule. This process is called annealing.
3. DNA polymerase elongation. The enzyme attaches to the primer-single-stranded DNA duplex and synthesizes the complementary strand of DNA, using the existing single-strand as a template.

Newly synthesized DNA strands can serve as additional template for complementary strand synthesis. PCR rapidly amplifies DNA; because both strands are copied, there is an exponential increase in the number of copies. Assuming there is only a single copy of the target gene before cycling starts:

After 35 cycles of PCR, there will be over 68 billion copies! In reality, PCR starts with many copies of the target gene, so the end result is typically higher. Each cycle only takes a few minutes. Factoring in the time to change temperatures, the entire process can be done in several hours.

More recently, a new method of PCR quantification called real-time PCR or quantitative real-time PCR (qRT-PCR) was developed [4]. qRT-PCR enables the detection and quantification of a specific DNA sequence using a fluorescent reporter (either a dye or a modified DNA oligonucleotide probe), which increases in direct proportion to the amount of DNA amplified in a reaction.

It’s easier to understand how PCR works with pictures. Visit DNA Interactive to view an animation of PCR. DNA Interactive is an award-winning educational web site created in 2003 to celebrate the 50th anniversary of the discovery of the DNA double helix structure.

The advent of PCR and recombinant DNA technologies have enabled numerous applications in basic and clinical research. PCR is often regarded as one of the most important scientific advances in molecular biology. Indeed, Kary Mullis holds the only Nobel Prize ever awarded to a scientist in the biotechnology industry. He received the Nobel Prize for Chemistry in 1993.

References

1. Saiki et al. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science. 1985 Dec 20;230(4732):1350-4.
   View abstract
2. Mullis et al. Specific enzymatic amplification of DNA in vitro: the polymerase chain reaction. Cold Spring Harb Symp Quant Biol. 1986;51 Pt 1:263-73.
   View abstract
3. Mullis and Faloona. Specific synthesis of DNA in vitro via a polymerase-catalyzed chain reaction. Methods Enzymol. 1987;155:335-50.
   View abstract
4. Higuchi et al. Kinetic PCR analysis: real-time monitoring of DNA amplification reactions. Biotechnology (N Y). 1993 Sep;11(9):1026-30.
   View abstract

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