Monday, October 31, 2011

Epigenetic clue to schizophrenia and bipolar disorder

Epigenetic factors have recently been implicated in certain psychological disorders, such as bipolar disorder and schizophrenia. Researchers noticed a difference in the methylation patterns of the gene ST6GALNAC1, which has been previously linked to schizophrenia, GPR24 which has been linked to bipolar disorder, and ZNF694 across 22 pairs of monozygotic twins. Interestingly, over-methylation of ZNF694 was associated with schizophrenia, and under-methylation with bipolar disorder. These new findings provide possible mechanisms of early diagnosis of psychosis, and further twin studies could allow greater resolution into the timing and causation of onset of psychiatric disorders.

A twin approach to unraveling epigenetics

This article from Trends in Genetics explores the significance of monozygotic twin studies in epigenetic research. Because MZ twins are identical in genetics, age, sex, maternal influences, and common environment, they provide a reliable, unbiased source for identifying epigenetic changes associated with complex traits. In particular, MZ twins showing disease discordance can be very helpful for disease research. The authors of this article lay out future direction and implications of twin studies in epigenetics, such as whether assisted reproductive technologies (which include IVF and can result in multiple births) affect epigenetics.

Epigenetics and stress

Professor Eva Jablonka of Tel Aviv University's Cohn Institute for the History and Philosophy of Science and Ideas reviews the current literature on epigenetics and concludes that it is possible to pass on acquired conditions such as stress and environmental damage to offspring.

Stressed dad = depressed children? Investigating the paternal transmission of stress

The article explored a study that explored the link between a father's stress level in his life and the effects that this would have on the children. The study wanted to know whether stress, anxiety, or depression would exist at higher levels if the father of the offspring was stressed. The study determined that the father's stress did play a role. Although environment was most significant factor for the development of stress, epigenetics did play a bit of a role--at least in mice. The next step is to see whether or not the finding will still hold true in humans. In the past, studies have looked at maternal stress levels only. The paternal stress levels had a greater effect on mice who were born naturally; this suggested that behavioral influence was more significant.

Sunday, October 30, 2011

Methylation Mutants = Phenotypic Diversity

Another A. thaliana epigenetics paper published a couple of months ago... and a different conclusion compared to that of Weigel's lab (see Shay's post on Epigenetics and Evolution). Ecker's team looked at epigenetic variation over 30 generations of A. thaliana and found an extremely high amount of epigenetic instability (high mutation rate), but also evidence for epialleles that induced phenotypic changes and were also metastable (heritable). Essentially, they concluded that epigenetic instability could be an important mechanism for generating phenotypic diversity.

Vaccine Cleared Again as Autism Culprit

One example of epigenetics that I think is very well represented in popular media is the vaccines and autism debate.  Many parents, supported by the pseudoscientific study done by Wakefield (described in this article), believe that the MMR vaccine caused autism in their children.  While most reputable science seems to point to the idea that the two are unlinked, the idea of this correlation lives on in the minds of many parents and continues to persist.  Basically the theory is that the vaccine epigenetically changes the expression of genes in the brain.

Great Website

The Learn Genetics website offered through the University of Utah has a bunch of great resources for epigenetics. Relevant to this weeks readings, you can "lick your rat pups" HERE, or watch a video about methylation changes across the lifespan in identical twins HERE.

BPA makes male mice less macho

BPA (bisphenol A) is a chemical found in many plastics that happens to mimic estrogen. Two recent studies have linked early-in-life exposure to BPA with feminized behaviors in adult male mice. In one study, BPA was fed to pregnant deer mice. The offspring were evaluated in terms of spatial and navigational abilities, as well as susceptibility to fear and anxiety. While males typically excel in such tests and females hesitate to explore, the male mice that had been exposed to BPA in the womb were "significantly compromised" in their abilities as compared to males that had not been exposed to the chemical. The female offspring did not appear to be affected by BPA. In the second test, mice were exposed to BPA in adolescence rather than in the womb. The male mice again exhibited feminized behavior, while females displayed abnormally exploratory behavior consistent with males. As one researcher commented, "These novel findings point to the fact that an early environmental exposure can manifest itself later in life...A likely mechanism is epigenetics."

Associations with early-life socio-economic position in adult DNA methylation

Related to Heijmans's paper we read for class, this study investigates ways in which poverty during childhood leads to certain epigenetic markers that might have an influence on adult health and risk for disease. These researchers studied the epigenome of 40 adult males who were involved in the 1958 British Birth Cohort Study, so characteristics of their childhoods and socioeconomic status are well documented among researchers. They used this data to see if there was any correlation between childhood socioeconomic status, and they found that indeed the adult's methylation pattern was more closely related to one's childhood socioeconomic status rather than one's adult socioeconomic status. Many of the regions where these associations occur in the epigenome are seen in "promoters of genes enriched in key cell signalling pathways," calling for more research to see how these altered methylation patterns affect one's adult phenotype and health results.

Saturday, October 29, 2011

Epigenetics and Evolution

I'm going to take you through a couple of steps here, but I promise it ends with empirical research! If you click the title of my post you will be linked to a brief notification regarding a recent study published in Nature by the Weigel Lab at Max Planck. The author seems to think that the only thing worth mentioning is that "epigenetics may not be that big of a deal.....would not have much of an impact on evolution in general". (For a real good time, read the comments). This briefing links you to a real news article summarizing a very interesting paper. The new article can be found HERE, and the PDF of the paper HERE.

Basically, the Weigel lab looked at the mehtylome of Arabidopsis thaliana (mustard weed, the Drosophila of plants) across 30 generations in 10 separate lines. They found that methylation of individual cytosines changed three times more quickly than the rate of DNA mutation. By contrast, wholly methylated regions (for example, at transposable elements), mutated at the same rate as DNA mutation. Additionally, the different lines showed similar methylation patterns.

So what does this mean for evolution? Well, we have to think about methylation that affects functional genes versus methylation that supports architectural integrity. Methylation at transposable elements probably keeps them from jumping, whereas methylation at an individual cytosine might be affecting the functionality of an exonic region. We are still in the infancy of understanding exactly how epigenetic mechanisms impact evolution, but I find the claim that "epigenetics are not important for evolution" to be sadly misinformed. Even when epigenetic marks are not as heritable as DNA marks, they have very important implications for the (non)heritability of traits! And that, my friends, has everything to do with evolution.

Friday, October 28, 2011

Revised Archon Genomics X PRIZE

It's now the the Archon Genomics X PRIZE presented by MEDCO. The competition rules have been revised - "The $10 million prize purse will be given to the first team that accurately sequences the whole genome of 100 subjects within 30 days for $1,000 or less per genome, at an error rate no greater than one per million base pairs." The 100 subjects are centenarians. These changes were implemented in hopes of generating more public appreciation for the project and giving greater medical value to the competition. The judging process will emphasize accuracy and completion in the hope that a "medical grade" genome can be produced, based on the guidelines recently published in Nature Genetics, vol. 43.

The announcement can be found on the Archon X website

Tuesday, October 25, 2011

Epigenetic control of vasopressin expression is maintained by steroid hormones in the adult male rat brain

The authors explored how steroid hormones affect methylation in the adult brain using a rat model. They castrated male rats, effectively removing their endemic source of testosterone. Testosterone exposure is necessary for the synthesis of vasopressin, so castration decreases vasopressin. However, castration also increases estrogen receptor α. They found that castration increased methylation of the vasopressin promoter and decreased the ERα methylation. These results suggest that the methylation of some steroid-responsive genes in the adult brain is maintained by the presence of circulating steroid hormones (in this case, testosterone).

Monday, October 24, 2011

A golden age for evolutionary genetics? Genomic studies of adaptation in natural populations

This article addresses the 20th century debate between the gradualist, incremental and the discontinuous, jerky theories of evolution. With current genome-sequencing technologies, we are able to investigate the patterns of mutation that characterize adaptive change. While there is significant evidence that single loci affect adaptive phenotypes in the wild, researchers still want to answer the question of gradual or jerky evolution. By means of QTL (quantitative trait loci) mapping and population genomics studies, epigeneticists can detect genetic substitutions that over time contribute to adaptive change, a phenomenon termed 'adaptive walk'. Because both quantitative genetic and population genomic studies have their drawbacks, a combination of the two would be ideal. In conclusion, researchers found that, despite Darwin's theories, single mutations can significantly affect phenotype.

Genome duplication encourages rapid adaptation of plants

The study, done by biologist Justin Ramsey who is at the University of Rochester, found that the number of chromosomes in plants can alter adaptability. Ramsey chose a plant that existed in two different climates: one a dry one and the other more moist. He noticed that the plants in the more dry climate had more chromosome sets and tested to see if the plant with less sets would be able to thrive in that environment to the same degree. The results proved that adding sets of chromosomes to the plants that grew in the moist environment allowed for them to survive in the dry climate to a greater degree than plants that were not altered. The study is fascinating because the plants were able to yield the same effects that regular genetic mutation has, which occurs over many years, in such a short amount of time.

Sunday, October 23, 2011

How evolutionary principles improve the understanding of human health and disease

One of the main differences across geography between different groups of people is their immune system and their resistance to disease. These types of differences lead to the question of whether these phenotypic changes between people is allelic or due to natural human plasticity. Epigenetics has confused this question: it now appears that there exist predispositions to certain diseases due to the inheritance of epigenetic markers that were added in very recent history to individuals faced with a certain situation in a certain time. These markers affect how children in very different environments may respond to stimuli despite the fact that these changes are not in the coding region of DNA and therefore will not be found by any SNP chip. Gluckman et al. argues that doctors, in looking to better understand diseases, will have to look at demographics, evolutionary biases, life histories, and family histories to begin to pull together a comprehensive theory of disease.

Population Genetic Analysis of the Uncoupling Proteins Supports a Role for UCP3 in Human Cold Resistance

Published this year, this study provides evidence that genetic variants related to temperature homeostasis in humans are correlated to climate. (It was actually cited in this week's Hancock paper!) By adjusting proton gradients within mitochondria, protein UCP1 helps regulate nonshivering thermogenesis (NST) in humans. This study set out to test whether SNPs associated with increased expression of UCP1 (and homologues UCP2 and UCP3) provide evidence of acclimatization. The SNPs were genotyped in 52 populations around the world, and correlations between allele frequencies and winter climate variables were calculated. The coding regions of the UCP genes were then resequenced in three different populations (Hausa of Cameroon, Han Chinese, and Italians) to clarify signals found in the genotype data. The results of the study suggest that climate adaptation shaped the distribution of UCP1 and UCP3 alleles.

Natural Selection Cuts Broad Swath Through Fruit Fly Genome

This article from a year ago describes an experiment on fruit flies that supports the hypothesis that evolution and adaptation is driven by multiple gene changes. Scientists at the University of California, Irvine, bred fruit flies through 600 generations and chose the ones that hatched first to be the parents of the next generation; such selection led to a 20 percent decrease in the time needed for hatching. After studying the genomes of hundreds of these flies, they concluded that this evolutionary change was driven by a soft sweep (where the trait is affected by many genes) rather than a hard sweep (where a single mutation is spread through the population). Following this view, Jonathan Pritchard of the University of Chicago explained that in human evolution, there seems to be many more soft sweeps than hard sweeps in adapting to new environments. This fruit fly experiment shows that such a mechanism is indeed possible for driving evolution.

Adaptive advantage of obesity gene

I thought the Myles article for this week was so interesting. If something even as ostensibly disadvantageous as obesity was specifically selected for by nature, it emphasizes the enormous role natural selection plays in who we (and all species) are today. Here is a study with rodents, which takes an opposite approach to the study of the origins of the obesity and the potential fitness the genes confer. They took rats, some genetically predisposed to obesity, and subjected them to strenuous exercise and starvation. All the rats under study lost weight, but the effects were much less severe and extreme in the rats with the obese genes, who also survived longer thus proving potential benefits of obese genes. In addition, they also found external influences had an effect on the expression of the obesity genes, particularly in homeostasis: rats that were exposed several times to the harsh, low-food, high-stress situations had a higher rate of survival, but tended to gain much more weight once normal conditions were regained. (Which explains the predicament of yo-yo dieters...) This study confirms the theory that obese genes were originally selected for to help individuals survive less abundant lifestyles than we are accustomed to today. Thus these genes, which are so valuable in environments with food instability, makes individuals in modern society far less fit, underscoring the fact that adaptation (and evolution) always has unfinished business.

Saturday, October 22, 2011

Recent evolution in response to natural selection in a contemporary human population

I just remembered this article I read from the NY Times earlier this month titled "Natural Selection Leaves Fresh Footprints on a Canadian Island". Parish records from the French-Canadian Island of Île aux Coudres have revealed an astonishing decrease in age at first reproduction (AFR, from 26 to 22 years) for women born on the island between the years of 1799 and 1940. Using powerful statistical tests, researchers were able to distinguish between cultural practices and natural selection, two potential drivers of this change. The unique social equality conditions of the island allowed for the detection of a clear genetic and heritable component to AFR. This is one of few studies to show convincing evidence for detection of microevolution over a few generations in a human population.

Climate change: Migration as adaptation

This study was part of the UK Foresight programme report on migration and global climate change. In the next 50 years, there will likely be increased migration of populations due to climate change. We need to give serious thought to our migration policies and consider the possibility that many people may not be able to migrate due to socioeconomic factors. The authors argue that "Migration may be the most effective way to allow people to diversify income and build resilience where environmental change threatens livelihoods. It is therefore necessary to make channels for voluntary migration available." Migration is adaptive in this changing world.

Friday, October 21, 2011

Why Your DNA Isn't Your Destiny

This is a really great TIME article that describes the basics of epigenetics as well as detailing the development of the theory of epigenetics as well as some key experiments in the field.  It especially details Bygren of Stolkholm's paper of the effect of starvation periods on lifespans of an individual's grandchildren.  It also describes a study of the effect of men smoking before puberty on their offspring.

Wednesday, October 19, 2011

Skeletal muscle function and gene regulation

This article describes the changes that skeletal muscle undergoes in response to physiological stimuli. Olson et al. identify the gene sox6 as a regulator of muscle constriction and metabolism. This was likely selected for in order to facilitate skeletal muscle function and dynamics.

Tuesday, October 18, 2011

Convergent adaptation of human lactase persistence in Africa and Europe

(This isn't my regular journal but a good article that I wanted to share, so I hope I'm not stepping on anyone's toes!)

The genes coding for lactose tolerance in Europeans is well known. However, there are populations in Africa that are also able to produce lactase beyond weaning but the genes coding for this have not been explored. Tishkoff and colleagues identify the SNPs associated with lactase persistence in these African populations, and find that it is different from those that code for lactase persistence in Europeans. This represents convergent evolution (and an adaptation) in humans as the result of strong selective pressure after the domestication of mammals.

Monday, October 17, 2011

Near Extinction for Humans

This National Geographic article describes a phenomenon that happened around 150,000 years ago before humans migrated out of Africa.  Because of drought conditions in Africa, the human population dropped to around 2,000 individuals.  These remaining individuals formed two population groups; one in south Africa and the other in east Africa.  These two populations lived in genetic isolation for nearly 100,000 years before recombining and moving out of africa around 40,000 years ago.

Ancient DNA sheds light on the origins of Early European Farmers

This article discusses a project undertaken by Professor Alan Cooper, Director of the Australian Center for Ancient DNA at the University of Adelaide. Cooper and his team analyzed ancient DNA from a neolithic graveyard in Germany, and found that the individuals interred there are genetically similar to Near Eastern populations, rather than European populations. This challenges previous beliefs that early neolithic farmers in Europe were descended from the European hunter gatherers that occupied the area prior to the establishment of agriculture.

Aboriginal Australians: The first explorers

The article discusses the origin and dispersal patterns of aboriginal Australians. After studying a hair from a modern day aboriginal man who lived in the early 1900s. Researchers discovered that the aboriginal Australians have no links to Europe and therefore are direct descendants of the first people who inhabited Australia. The researchers seem fascinated by the fact that these Australians have had ties to a specific region longer than any other group. People were also fascinated by the fact that these people had to be very skilled explorers to be able to get from Africa to Australia at such an early point in history. This study disproved the theory that Australians descended from Asian or European explorers because the aboriginal Australian dates back to about 24,000 years before early Asians and early Europeans differentiated from one another.

A negative perspective on the Genographic Project

This article is a bit older (sorry!), but I felt it warranted review. It is a response to the announcement of the Genographic Project from an indigenous rights attorney. In summary, the article is a classical sociocultural versus biological debate. She is worried that this project is too reminiscent of the Human Genome Diversity Project--a similar project from the '90s that failed to obtain national funding due to bioethical problems. While it is certainly important to protect the rights of indigenous peoples, I believe the author goes a bit too far in her claims that the Genograhic Project will harm these people and the cultures the people are trying to preserve. For example, she says "Despite the speculative nature of genetic research on human histories, the findings of the Genographic Project will carry the weight of science, which could be used to trump indigenous peoples' unique political status and rights".

There are two aspects of this statement that are troubling. The first is the claim that genetic research on human histories is "highly speculative". This shows a misunderstanding of what genetics can tell us. Admittedly, our methods are improving daily and have come a long way since 2005. This doesn't negate that in 2005 we still had quite a solid foundation for the Genographic project (much more solid than in the '90s, to be sure), which is being willfully ignored by the author. The second problem is the notion that big, bad science will come in and "challenge the 'indigenousness' or 'aboriginality' od certain indigenouse populations...". This reads to me like a case of sciencephobia. The notion that an institution like National Geographic will use science to harm indigenous populations is simply ludicrous. It also further reveals her misunderstanding of what kind of "genetic information" is being sought, and what it can tell us. Understanding migration patterns has no bearing on the sociopolitical concept of "indigenousness". In fact, the Genographic Project is directly assisting the preservation of indigenous culture, an example of which is shown HERE.

Sunday, October 16, 2011

Reconstructing the genetic architecture of the "extinct" Taínos

The Taínos were the first Native Americans to meet European explorers in the Caribbean, and as the all too familiar story goes, they were completely wiped out by European disease and violence. Carlos Bustamante from Stanford University has begun to elucidate the genetic structure of this extinct ethnicity from the genomes of modern Puerto Ricans. The inclusion of 70 modern Puerto Rican sequences in the 1000 Genomes project has revealed a mosaic of African, European, and Native American (Taíno) DNA. By estimating the length of African, European, and Native American DNA segments, Bustamante has been able to reconstruct the timing and duration of admixture events. As expected, segments unique to Taínos indicate a short burst of admixture which concurs with historical facts (Taínos were likely extirpated soon after the arrival of Europeans). The African and European segments are quite variable and suggest several waves of migration. The analysis is only in it's preliminary stages, and Bustamante hopes to gain further insight into the ancestral Native American genome.

Mitochondrial Eve vs. Biblical Eve?

Since the days of alchemists, science and religion have always been in conflict, as science always seems to be uncovering information which threatens a literary interpretation of texts like the Bible. However, the tension between science and religion is somewhat relieved in the mitochondrial Eve and the migration from Africa theory. This article describes how the estimated time line for the existence of "Eve", the first female human, is consistent between estimations from the Bible and the evidence from mtDNA. In addition, the amount of genetic variation and higher rates of linkage disequilibrium that exists in the world, assuming constant mutation, is far less that what one would estimate, which supports the idea of The Great Flood followed by subsequent bottle-necking.

Early human migration written in stone tools

This article from Nature discusses the recent discovery of ancient stone tools at Jebel Faya in the United Arab Emirates. Researchers unearthed three collections of broken and unfinished hand-held axes and leaf-like blades, the oldest of which has been dated to 95,000 to 125,000 years old. They believe these tools resemble those of early humans rather than those of our archaic relatives. With genetic evidence suggesting dispersal from Africa at around 60,000 years ago, the discoverers of the Jebel Faya tools incited controversy when they claimed the tools' makers may have actually been modern humans. Many archaeologists maintain that the tools must have been created by our archaic relatives, but as one Jebel Faya team member said, "The idea that they left Africa at 60,000 and ended up at Australia at 50,000--my God, did they ever stop running!"

Yersinia pestis genome sequenced from victims of Black Death

The DNA of Y. pestis, the bacterium responsible for Black Death (BD) that swept across Europe from 1347-1351, was isolated from the dental pulp of several BD victims (exhumed from an established BD burial ground). 30-fold sequence coverage was achieved for the genome, and phylogenetic comparisons with other modern Y. pestis genomes revealed that all strains of Y. pestis originated in medieval times, with the BD strain representing one of the most basal strains. Interestingly, there were no derived substitution positions in the BD strain suggesting that the seemingly increased virulence attributed to this strain's potency was likely due to other factors such as the host's genetic background, climate, social conditions, and vector dynamics.

Continents Influenced Ancient Human Migration, Spread of Technology

Researchers at Brown examined migration patterns across Eurasia and the Americas, trying to determine how population mixing varied between the two. It was known that in Eurasia, people tended to move in an east-west manner, taking advantage of the fact that climates are very similar as they moved laterally. However, the Americas are arranged in a more north-south orientation, spanning many climates from top to bottom. As suspected, this configuration appears to have limited migration and inter-group dynamics, as it was discovered that genes of isolated populations in the Americas varied more than those in Europe. It is thought that migrations occurred less in the Americas because it is more difficult to transverse different climates than to move along a temperature band.

Saturday, October 15, 2011

1920s hair sample reveals Aboriginal Australians' explorer origins

Eske Willerslev led a research team that sequenced the genome of an aboriginal Australian individual from a 90-year old hair sample. Genetic analysis led to the conclusion that "Aboriginal Australians descended from the first human explorers," said Willerslev. This Aboriginal Australian individual was shown to be a descendant of the first human migration out of Africa over 60,000 years ago, since genetic analysis of his genome points to a divergence from other human populations at 60,000 years. Willerslev calls this migratory population the first explorers and that they must have possessed "exceptional survival skills and bravery" to have traversed over such a long distance to reach Australia. Another article on this study ( discusses that the modern Aboriginal Australian population was very excited upon hearing the results of this study, since it validates their strong connection to Australian land by "[establishing] Aboriginal Australians as the population with the longest association with the land on which they still live today."

Wednesday, October 12, 2011

One Man Fathering 150 Children? Why Sperm Banks May Be Unethical

Here's an interesting article that discusses some of the issues we were talking about in class on sperm donations. One sperm donor, who donated anonymously, later found out that he has 74 biological children. He also found a website that helps donor-children find their biological fathers, and used his "donor number" to reach out to people looking for him.

Tuesday, October 11, 2011

Hunter-gatherer genomic diversity suggests a southern African origin for modern humans

Contrary to previous studies of genetic diversity in Africa, this study claims that the modern human origins can be traced to Southern Africa. The authors analyzed genome-wide SNPs of hunter gatherers (Hazda, Khoisan, etc.)and 21 other African populations. They found that the best fit model using linkage disequilibrium for location of origin is in southwestern Africa. This is a surprising results, as most other reviews of genetic diversity would place this origin in Eastern Africa.

Monday, October 10, 2011

Personal Genomics in 2011

This article looks at the 'personal genomics landscape' for 2011, and evaluates how the field has progressed since 2010. They raise some very interesting point, especially about the $1000 genome. Specifically, they address the costs of analysis. Sure, you can get a $1000 genome sequence but it will cost "another $100,000" to analyze the data for an individual person. Does this make the personal genome any more accessible for everyday, healthy people? They also address whether the personal genome will stay DTC, and the issues surrounding patents, legislation, and ownership of data. It is a nice starting place for a more updated version of our Gurwitz & Bregman-Eschet reading.

In general this looks like a great site for getting more information about the societal impacts of the genomics revolution (

Disclosure of individual genetic data to research participants: the debate reconsidered

In this article from Trends in Genetics, authors address the ongoing debate of whether or not researchers are morally and ethically bound to release data to participants of genetic studies. The question of disclosure becomes more difficult in genetic studies because the participants are not entering the study with the expectation that they will hear results, which differs from a personally-requested whole-genome sequence or specific gene sequencing from 23andme, for example. Debate currently stands in two fields, restrictive disclosure policy ('no, unless') and qualitative disclosure policy ('yes, if'). Key among this debate is the argument of beneficence, which says that researchers are morally obligated to reveal genetic results to participants if the results will prove valuable to the patient, i.e. life-saving. Authors note that it is interesting how the two extremes of "no disclosure whatsoever" and "full disclosure" are not included in this debate.

How 'personal' is personal genomics?

An editorial in Science this week addresses the 'gaping hole' that still exists in genomics - that is, our lack of knowledge of the biological mechanics behind genetic disease. Greater attention must be turned to systems biology, Chakravarti states, and asks the question: if each individual is genomically unique, then is each individual's biology and disease also unique? Does this lack of understanding of individual biological response to disease causing genetic mutations indicate that personal genomics is not quite as personal as some would hope?

Personal Genomics and Public Health Initiatives

This article reviews a report published by an international panel of experts from a wide variety of fields including medicine, law, bioethics and public health.They investigated the potential for the use of genomic medicine in global public health initiatives. The report concludes that international efforts to utilize personal genomics in medicine are called for, especially with regard to developing countries. They also call for the creation of a public, global database of personal genomic profiles for the purpose of furthering knowledge and investigations into genomic medicine.

6th Annual International Translational Medicine Symposium held at Penn

The article is a glimpse into a conference that is going to take place from October 18-19 at University of Pennsylvania's Medical School. The whole conference is not about personal genomics but a significant portion is--especially towards the beginning of the conference. The specific question that is being posed is: "As access to personal genomic information becomes more widespread, is there more to understanding disease risk and response than simply knowing your genome?" The question is going to be tackled by two different perspectives from across the world. The conference will be streamed online and potentially these speakers will be available for a conference call after their panel. The website to the conference is:

Gut bacteria affects the brain

Recent studies have suggested that the host's gut microbiota may affect the brain and behavior. A study's results showed that mice fed a broth containing Lactobacillus rhamnosus were less anxious than mice fed sterile broth. The bacteria-fortified mice also possessed a unique GABA receptor distribution profile in the brain as compared to that of sterile broth-fed mice. Interestingly, when they cut the vagus nerve in the mice fed bacteria, they returned to an anxious phenotype similar to that of their sterile broth-fed brethren. The vagus nerve may be an important pathway for inducing behavioral effects caused by gut bacteria.

Sunday, October 9, 2011

Nature - Personal Genomics

Here is a neat article about personal genomics that was published 4 days ago online in Nature. It basically contains statistical data on the opinions of their readers on similar ethical discussion questions to the ones we went over the first day: whether people would be interested in having their genome analyzed (only 15% said no outright), the majority said they would have it done out of curiosity, rather than as a test for a particular disease or concern. I was pretty surprised that 10% had gotten their whole genome sequenced, and 16% had gotten their exome sequenced, but as the article says, many of their readers are scientists themselves so the data is skewed. I was also taken by the author's choice of words in describing the decision to have one's exome sequenced and stored as giving our cells "immortality", because it really hits home the gravity of having our DNA sequenced and having that information exist on a server somewhere out in the world. (And eerie as the company is located in Tucker, Georgia, which reminds me of Tuck Everlasting...)

Ownership of Genes

This article discusses the 2010 court decision to make patents of genes illegal.  The specific court case was over the 'ownership' of the BRCA1 and BRCA2 genes.  Before this case, Myriad had a patent on these two genes which meant that they were the only institution allowed to sell tests for mutations on these genes.  The court decision said that such a monopoly would not be allowed.  However, this decision brought up interesting implications for the patentability of protein-based drugs and antibiotics.

Personal genomics: information can be harmful

This commentary asserts that while personal genomics information can be very helpful, its harmful potential deserves careful examination. The authors state that harms from information are extensive in clinical medicine (e.g. undesirable side effects fostered by "labelling"), and that the "net harm" or "net benefit" of such information must always be taken into consideration. They express concern that the typical careful examination of new biomedical technologies has not been applied to DTC marketing of genomic profiling, and that the assumption that information can only be helpful is far too common and must be corrected as we learn more about personal genomics.

Saturday, October 8, 2011

Faroe Islands' FarGen Project to Sequence Genomes of Entire Population

The Faroe Islands, a territory within Denmark, has plans to sequence the genomes of each of its 50,000 inhabitants in a new project titled FarGen. A pilot program will begin with 100 people, and the entire project is expected to cost $47 million. The project aims to connect each individual's genome with their health records and to make this information available, with certain restrictions, to physicians. This project is especially supported on the Faroe Islands due to the high percentage of genetic disease among their population. The project will also develop a genomics education program throughout the nation to "address the issue of informed consent." Eliasen, of the Faroese Ministry of Health who announced this project, explained "if successful… the Faroe Islands could serve as a global model for implementing whole-genome sequencing into a healthcare system."

Nature Survey on Personal Genomics

A few months ago, Nature opened a survey asking their readers about their attitudes on personal genomics and if they had been involved with personal genomic testing. Of the 1,588 people who took the survey, 18% have had some sort of genome analysis, and 54% of the respondents said that even though they haven't had genome analysis, they would do so if given the opportunity. 50% of those who had genome analysis used the services of 23andMe. Interestingly, intellectual curiosity was one of the highest motivators for genome sequencing, along with medical and general health concerns. More survey results appear on their website.

Britain to launch personalized medicine project

In the United Kingdom, the Cancer Research UK has begun a pilot program for mass genetic screenings of cancer tumors. They plan to take the excess component of biopsies and make a library of genes and mutations in the tumors in the hopes of gaining and understanding of which treatments will be effective on what cancer types. The benefit of a centralized system is that it allows for many researchers to have access to samples but also maintains standards of patient privacy. There also exists the hope that this will provide a model for bringing further personalized medicine into the British healthcare system.

Wednesday, October 5, 2011

Ethical Dilemmas of Genetic Research

At the 4th annual Personal Genomes conference, the ethical dilemmas surrounding genetic information disclosure to subjects involved in genome research was debated. Currently, federal law prohibits research facilities to reveal genetic information to subject unless a certified clinical lab has confirmed the results.

Very much relevant to next week's discussion on personal genomics!

Tuesday, October 4, 2011

Misfolded human tRNA isodecoder binds and neutralizes a 3′ UTR-embedded Alu element

The authors of this article demonstrate how two kinds of RNA, tRNA and Alu RNA, interact. tRNA binds to Alu RNA, causing a rearrangement of 3' UTR. Because of the large number of Alu elements and diversity of tRNAs in humans, they propose that this is a posttranscriptional regulation mechanism that might be unique to primates.

Monday, October 3, 2011

"Outbreak Detectives Embrace the Genome Era"

In Science this week: A team of scientists met in Brussels to discuss the creation of a global database where the genomes of disease-causing mircroorganisms could be shared as soon as they surface. In this way, it is hoped, the centre of disease outbreak can be pinpointed, antiobiotic effectiveness can be determined, and the evolution of microbes monitored.

Shows what the public fear of epidemics (seen 'Contagion' yet?) plus 'literally..more money than God' can achieve.

HGP is 10: the gene therapy challenge

This article addresses the implications of a completed Human Genome Project for gene therapy. It uses the case of cystic fibrosis, the "most common life-threatening single-gene disorder," to illustrate some hurdles to effective gene therapy. The benefits of using a human promoter sequence (rather than that of a virus) in the therapeutic plasmid are discussed, as well as how details down to the plasmid's exact DNA sequence can greatly affect the efficacy of the therapy. Dr. Deborah Gill of the UK Cystic Fibrosis Gene Therapy Consortium says that the HGP has "provided all the tools to make things really easy" and has "revolutionized gene therapy on a support basis." If greater efficiency in gene transfer and a longer response are priorities, how can the information of the HGP be exploited to indeed "revolutionize gene therapy"?

In quest for new therapies, clinician-scientist team unlocks hidden information in human genome

The article talks about how a science researcher and a physician team up in order to study genetic mutations in the human genome to see if these mutations caused diseases. The two, analyzed how the "lock and key" mutation takes place: "the 'lock' – a segment of DNA known as the CArG box – and the 'key' – a protein known as SRF – come together or bind, they unlock the ability of a cell to turn on a gene." The results of their research left unclear which disease the mutations affected although the two were able to link certain mutations to other health issues such as type 2 diabetes. The goal is to find out the issues and solve them at the molecular level so that people with not have to have certain life-threatening diseases.

Sunday, October 2, 2011

1000 Genomes: A World of Variation

The 1000 genomes project is working to sequence the genomes of at least 1000 individuals in the hopes of discovering 95% of the variation that occurs in at least 1% of the population. Already, it has located 15 million SNPs, 1 million short indels and 20,000 large structural variants, for a total of over 16 million variations, half previously unknown. Because many diseases are not the product of one gene, such a widespread database of variation could help researches connect many genes and allelic differences to any given gene. Some researchers also hope that by continuing the project past 1000 genomes and including related individuals could help clarify genetic components to these diseases.

Genomics and Human Disease

Using data from the 1000 human genome project, these researchers are suggesting that recent mutations are more involved in disease protection or susceptibility rather than ancient mutations.  They attempt to present a unified theory of genetic disease that encompasses both common and rare Mendelian, multiple allele, SNP, and copy number variation mutations.  Especially important in their observations is that many diseases are caused by rare alleles, signifying that mutations in the last two generations have a huge impact on disease.
Also, this is a news article that discribes the research as well.


Researchers at Stanford University School of Medicine have found that they were able to identify where on the chromatin regulatory RNA’s are acting. They utilized new techniques to elucidate the binding specificity of lincRNAs from fruit fly and two mammalian species. They found that these sites are “focal, numerous and site specific”.

The Human Genome Project, Then and Now

In this article, a researcher analyzed specific quotes from his own article, written in 1986, in which he discussed his optimistic predictions for the human genome project. In general, it seems that all of his goals for the project did come to pass, like a database and determining key genes involved in disease. It's interesting that we have even surpassed some of his predictions. (Although I wonder if they perhaps only chose his points which came to pass?)

Speed-bumps ahead for the genetics of later-life diseases

This article expands on the ideas of Eric S. Lander by investigating further into the genetic makeup of common disease, with a focus on later-life diseases. With age as the dominant risk factor for many diseases, researchers want to know what role genetics play in the aging process. Chance plays a large part in late-onset diseases because of the weakening of natural selection, the complexity of late-life traits, and the fact that aging is largely determined by molecular and cellular damage. While GWAS have revealed a number of genes associated with diseases such as Alzheimer's, researchers suspect that there are many more genes with smaller effects that collectively cause ageing.

Richard Resnick on the Genomic Revolution

Richard Resnick weighs in on moral issues associated with the genomic revolution. A decade has passed since our 2 cornerstone readings for this week were published, and the consequences of the Human Genome Project are unexpected and varied. Resnick goes through some of the reasons why this information has transformed our society (mostly through medicine) for the better. On the flip side he evaluates the realized negative consequences of this information, and predicts imminent problems that we, as citizens of humanity, will soon face. Can you think of anything that he did not cover in this talk that you feel exemplifies either the 'pros' or 'cons' of the genomic revolution?

Mouse genomic variation and its effect on phenotypes and gene regulation

This research team sequenced the genomes of 17 different mouse strains, creating the largest genetic database for any vertebrate organism. 56.6 million SNPs were identified in the mouse genome, and some of these mutations have been related to various disease phenotypes including heart disease and diabetes. Since mice are used in a lot of research for human disease and cancer, it is important to understand their genome and the mutations involved in order to relate this research to human disease. Now, researchers will be able to use a programmed computer mouse, instead of actual mice, to study mutations and particular genetic diseases. One of the researchers, Ian Jackson, said that this study "is transforming our understanding of how DNA sequence variation relates to gene function, and ultimately its association with biology and human health."