"The uncertain road towards genomic medicine"

Hey guys,

My potluck for this week about the challenges we will need to overcome in genomic medicine.  It covers some interesting technology-in-progress examples, including discussion of a USB drive type of device that can give someone an accurate reading of his or her DNA.  The paper then discusses how genomic medicine is not just about predicting disease from genetic variation, but how it has a large influence by environmental effects as well.

http://ac.els-cdn.com/S0168952512000698/1-s2.0-S0168952512000698-main.pdf?_tid=a6f1ab4a-8111-11e2-a0bb-00000aacb360&acdnat=1361992539_611b32ee76769f2c598175e493390e95

2/27 Potluck -- Genetic Dsicrimination

Hey guys,

Here's a site by the National Human Genome Research Institute.  It talks about genetic discrimination and the Genetic Information Nondiscrimination Act which protects people from discrimination from potential employers and health insurance companies.  http://www.genome.gov/10002328

Potluck 2/27 Genes Role in Social Behavior

A new study found that genes can actually play a larger part in social behavior of species or groups of a specie than previously believed. This study addresses the question of nature versus nurture within primates. Initially, it was believed that environment was the primary reason for differences between species. It was also believed that even within species of primates, groups that live in different environments would behave differently. However, according to a new study, it is actually genes that have the most effect on different social behaviors between species rather than environment. The study, done by scientists at Oxford University, claims that even groups of the same species that live in different environments would have the same social behaviors. One example the study gives is Old World Monkeys. Although they live in environments ranging from savannas the the rain forest to alpines, the social behaviors amongst them are the same.

NY Times Article

Approaches to Genomic Privacy

My potluck for this week echoes and provides an update on the paper Elisa posted about individuals' detectability in large samples.  This paper in Science magazine a month ago determined that not only can SNP profiles of individuals be parsed out of large sample sets, but that personal identifying information can be matched up to anonymous samples by comparing those samples to genetic geneology databases.  This means that not only are consent issues prevalent when donating a sample to a biomedical research database, but even that private donations for one's own interest (for instance, in his or her family history) can be traced and linked to other genetic information.  And I know Joan already posted this paper, but since it is largely in response to the types of privacy concerns made explicit in the science article, I thought it would be worth while to post again.  It argues that since these types of privacy problems are exacerbated by claiming anonymity (which cannot be guaranteed), that it is better to tie personal information to the samples and thus claim protection under legislation designed to regulate genomics research.

Treatment-oriented medical benefits of personal genomics

This article discusses a few medical benefits of personal genomics in a treatment-oriented medical context (as opposed to a preventative-focused context). One patient sequenced her tumor's genome and was able to effectively fight her previously resistant cancer. (The tests revealed "abnormalities in genes not typically associated with breast cancer, including one that activates a cancer-associated protein called mTOR. The drugs [blocked] the growth-stimulating activity of that protein.") Such genomic sequencing is not regularly covered by insurance, which prompts questions about controlled access. Cancer patients often face lengthy trial-and-error periods with their treatment regimens... Assuming genomic sequencing will never be cheap, is there a point at which cancer patients with insurance should be able to get genomic sequencing performed to stave off ever-worsening diagnoses?

The parents of a different patient with an undiagnosed developmental disorder decided to undergo full exome sequencing along with their daughter with the hopes of identifying her condition. Such an identification would have positive benefits for the family including easier access to medical services or therapies. Are there any negative repercussions involved in this decision?

On a different note, one of the doctors in "Grey's Anatomy" (a popular modern soap opera medical drama) recently petitioned to genome sequence a patient's tumor... While this storyline did not occur in the most scholarly of contexts, I do think that it shows how genomics is slipping into mainstream culture. (Here is a link to an article written by the show's medical researcher explaining genome sequencing for the masses.)

The Warrior Gene and Genetic Determinism

This article is one of many contributing to an intense debate about a controversial scientific publication associating "warrior-like" or aggressive tendencies (including alcoholism) among the Maori with their genes. Not only has this "finding" been criticized as downright bad science, it has also been passionately discussed as a seed of scientifically justified racism. Most of the early articles associated with this finding overlooked the socioeconomic factors (of which there are many) that are much more clearly responsible for some of the complicated social and familial issues that have been statistically prominent among the often oppressed Maori communities of New Zealand and Australia. This is a crucial example of the risks associated with the dispersal of genomic information in the technological age and reminds us of the importance of very carefully considering the social implications of the research published in the field of primate genetics/genomics.

http://www.tandfonline.com/doi/abs/10.1080/14636778.2011.597985

2/27 Potluck

THIS article by David Craig shows that an individual can be identified in a large population's SNP data.  This has important implications because, before this article, conglomerated SNP data was being made openly available online.  Using a program and an individual's SNP profile, you can tell if that individual is present in a larger sample. This has important implications for privacy.

MHC, Mate Choice, and Fitness

In light of our discussion of adaptive variation and MHC last week, I thought this might be an interesting article:

http://rspb.royalsocietypublishing.org/content/275/1634/555.full.pdf+html?sid=e5ace2c2-e9e3-4029-b9b3-ab75a6b17dd8

Based on study of the promiscuous grey mouse lemur in a wild population, the authors conclude that while no pre-copulatory MHC driven mate choice was evident, it was clear that there was post-copulatory mate choice in favor of MHC diversity between the mother and potential fathers. They further propose that some degree of cryptic female choice may be at play to promote immune diversity among offspring.

DNA Test for Rare Disorders Becomes More Routine

DNA Analysis, More Accessible Than Ever, Opens New Doors
Here is another NYTimes article, this one directly related to tomorrow's readings.  In it, a family whose two sons have been affected by serious and rare genetic disorders.  Their first son, Jacob, has Angelman syndrome while their second son, Eli, has an extremely rare condition (less than 10 cases have ever been documented) which resulted from a single base mutation in the CASK gene.  While their first son has severe developmental delays, Eli's condition will require life long dependent care.  Eli's condition was repeatedly misdiagnosed until his parents learned of DNA sequencing.  The parents have since made it their mission to promote genetic sequencing to other parents of children with developmental delays.  They say it will lessen the confusion, stress, and costs of repeated misdiagnoses, cross-country visits to multiple experts, and failed treatments.

A Letter from Francis Crick

A DNA Lesson, From the Expert's Pen
I found this article this morning in the NYTimes Science Section and thought I would share it.  It's not exactly relevant to what we're learning, but relevant to genetics very broadly and just really cool!  There is a letter from March 19th 1953, 2 weeks after Crick & Watson discovered/realized how the bases of DNA pair up in the double-helix structure, on auction (estimated $1-$2million).  In it, Francis Crick explains DNA's structure and function, with special attention to replication, to his 12 year old son and sketches out a picture of the double-helix.  He begins the letter "Dear Michael, Jim Watson and I have probably made a most important discovery" and signs it "Lots of love, Daddy".  Here is a transcript to the full letter

This Week in Science

THIS Science News article shows coevolution between the human microbiome and human culture.  It shows how the agricultural revolution changed the bacteria that colonized the human mouth, leading to increased cavity causing bacteria.

Other than that, there were many articles on human health policy (that didn't seem very applicable) as well as THIS really cool article about how the evolution of behavioral immune responses in fruit flies.

"Our Robust Intellect"

Hey everyone,

I am monitoring Trends in Genetics this semester for our class.  I found a paper released on Monday February 18^th that is sort of relevant to some of our class discussions (FOXP2 gene, transposon mutagenesis and scientists bashing the works of other scientists are found here).

In a nutshell, this paper was a response to a paper by Gerald Crabtree, who claimed that our human intellect is inevitably declining over time due to retrotransposition events that cause a loss of heterozygousity in a beneficial variant of neuron-related genes.  Crabtree claims that this, therefore, makes intellect less heritable.  This paper proves that there is no link between changing intellect and heritability.

http://download.cell.com/trends/genetics/pdf/PIIS0168952513000206.pdf?intermediate=true

This week in Nature

Hey 420,

This week in Nature there were a few pieces that might pertain to our class material:

1.  A snapshot of some research on some single-letter mutations in the human genome that have been under selective pressure in the past 50,000 years, including mutations that seem to influence the immune system. http://www.nature.com/nature/journal/v494/n7437/full/494284b.html

2.  Another snapshot of some research done on the decline in egg-cell quality and the ability to repair DNA as women age. http://www.nature.com/nature/journal/v494/n7437/full/494284c.html

3.  One last snapshot of some research done on DNA-binding proteins.  http://www.nature.com/nature/journal/v494/n7437/full/494285b.html

4.  A bit of news on Gene sequencing technologies... making it cheaper and more practical to do sequencing more readily.  http://www.nature.com/news/gene-sequencing-leaves-the-laboratory-1.12454

This Week in Science

This week had a whole bunch of papers in Science that were at least mildly associated with the classes scope--or just pretty interesting.

1) A perspective on the creation of a molecular animal tree of life, including some of the surprises associated with its creation: HERE

2) A perspective on the role of new insights from biophysics into gene regulation--specifically the role of adjacent DNA bound proteins and their allosteric effects:  HERE
And the full length research article: HERE

3) A perspective on new ideas in gene therapy to create more targeted approaches using RNA-guided systems: HERE
And two full length research articles: HERE1 and HERE2

4) A comment and a response to a comment from a previous paper on "Evolutionary Trade-Offs, Pareto Optimality, and the Geometry of Phenotype Space" that showed how 'configurations of phenotypes may identify tasks that trade-off with each other': HEREC and HERER

Human Culture in Primates

It has been widely accepted that social interactions and culture that we experience is something that differentiates humans from primates. However, a recent study in South America shows that there are some monkeys who have been able to learn skills through social interactions. The example given is that when a predator is spotted, one monkey will begin banging a rock to make a loud noise. While this is seen as a way to scare off the predator, it also is a way to warn the other members of the group of the predator. However, it was also noticed that even without a predator in sight, older and younger monkeys were seen banging rocks as though the older monkeys were teaching the younger ones. The article highlights that this rock banging is seen as a way of communication between the monkeys as well as an example of social learning, which scientists were/are not sure is possible within primates.

http://www.eurekalert.org/pub_releases/2007-03/uoc-neo032307.php

Discovery of Genes that Make us Human

Gene Discovery

This article focuses on what it is about our genes that makes humans different from primates and all other mammals. The study found that while it is known that mutations in genes from duplication and rearranging is what creates new genes, one of the main reasons we may differ from primates is actually because of non-coding DNA. Looking at the genes of primates the study has found that some of the differences is actually that non-coding DNA in primates has actually become active within humans. So, while some of the same gene may be inactive in primates, when it was transcribed, it became active which helps account of differences between humans and primates.

This Week in Nature

Hey 420,

A few articles in this week's Nature issue pertain to some topics we've discussed in class.

Here is a piece, again, on the ethics of genome sequencing humans: http://www.nature.com/news/genetic-privacy-needs-a-more-nuanced-approach-1.12363

Next is a piece on environmental conditions influencing evolutionary change: http://www.nature.com/nature/journal/v494/n7435/full/494009c.html

Last is a piece on the possible effects epigenetic changes on sexual maturation in female mammals: http://www.nature.com/nature/journal/v494/n7435/full/494009d.html

Color Vision in Birds

Similar to Sam's post about ultraviolet sensitive vision in aye-ayes, I found an article tracing the genetic roots of ultraviolet sensitive vision in birds. Posted just a few days ago, a study conducted on 40 bird species reveals that ultraviolet vision in birds evolved due to single nucleotide changes. In birds, there are two amino acid alterations that can change color vision in birds, and one particular SNP occurred at least 11 different times!

This Week in Science

This paper describes Harvard archaeologist John Shea who has proposed that human cognition has not changed much since the species homo sapien arose and that the more 'complex' culture that we see today is really just a product of different environmental challenges.

This paper called Fossils Versus Clocks details some of the challenges and benefits of using either method to determine dates of speciation and emergence of species.

This paper used molecular phylogenetic analysis to determine the placental mammal ancestor and the geographic spread and speciation of major clades of placental mammals after the Cretaceous-Paleogene boundaries.

This Science News article shows that the appendix evolved over 30 times in mammals.  They did this by mapping species with the appendix onto a phylogenetic tree and seeing that these species were spread out all over the tree.

Convergent Evolution of Lactase Persistance

I was reminded of This Nature Genetics article while reading the Zhang article. This shows convergent evolution in different human populations in response to lactose in the diet.  The actual mutation is not the same between the populations, but they do affect the same gene and arose at least twice (probably more) during human history.

Why Aye-Ayes See Blue

Why Aye-Ayes See Blue
This was a really cool article about why the Aye-Aye has not only retained its color vision (many primate species are colorblind) but also why its color sensitivity peaks in the ultraviolet region of the color spectrum.  Scientists are unsure why the Aye-Aye is particularly sensitive to the color blue, and are even more intrigued in their ability to see colors at night (all mammals were believed to be colorblind at night).  They believe this unique ability to detect colors at night might be due to the presence of albeit limited light at twilight and during full moons.

Transposable elements in pregnancy

http://bfg.oxfordjournals.org/content/early/2012/06/28/bfgp.els013.full This paper isn't as recent as some of the others we've looked at on pot lucks, but I think this is a really tangible example of a few mutations with profound adaptive effects. Professor Wagner discusses how transposable elements cut and pasted regulatory elements to the effect that many placental genes were expressed together to create placental pregnancies. Furthermore, he elaborates on how these types of mutations could respond quickly to environmental changes, thus allowing them to function uniquely in clades like primates. Scanning genomes for spliced regulatory elements by transposons might provide researchers with other examples of rapid adaptation by few mutations.

"Dynamic functional evolution of an odorant receptor for sex-steroid-derived odors in primates"

Hi all,

As we talked about two weeks ago, sensory elements account for most of the genetic differences between humans and the other primates.  One example of this is the OR7D4 gene, which is an odorant receptor for androstenone and androstadienone and produces physiological changes in humans.  This test was performed to see the effects in sensitivity of the OR7D4 gene in various species because little is known about the functional changes of individual odorant receptors during evolution.  What they found was a huge range of functions and responses for each primate.  However, it is not clear whether most of these changes are actually adaptive or not.

Link: http://www.pnas.org/content/106/50/21247.full?sid=a85e02fd-6bc5-4bc1-9bd1-5056b2f52d16

Michael Cruciger

Human pigmentation -- MC1R phenotypic variation

This article discusses the correlation of two SNPs upstream from the MC1R pigmentation gene with different spectra of pigmentation in human eye, hair, and skin color.

http://onlinelibrary.wiley.com/doi/10.1002/ajhb.22301/full

It is a nice example of the role of regulatory evolution in the expression of diverse phenotypic characters and highlights the influence of ecological and environmental factors on genetic processes of adaptive variation. These findings also have interesting implications for anthropology and forensics.

Proc. Royal Soc. B -- adaptive facial coloring

In light of our discussion of adaptive phenotypic variation, I thought this Proc. of the Royal Society B article would be an interesting point for discussion:

http://rspb.royalsocietypublishing.org/content/279/1736/2204.full.pdf+html?sid=673ed8bf-b85e-4b1a-8961-5bfbb8dc40c6

The article explores the convergence of evolutionary, social, and genetic factors in the discussion of what drives the remarkably diverse displays of primate facial coloring. The article suggests that facial coloring is powerfully driven by the need for more complex patterns of social recognition especially among sympatric groups with overlapping ranges and that some of the most diverse displays are observed under these conditions. It also proposes a more fluid model for understanding the genetic processes underlying changes in facial coloring. In the past facial coloring has been understood as a more "permanent" evolutionary adaptation, but the alternative biological pathways supported by these authors' data involve more evolutionary flexibility, allowing for more variation in phenotypic displays over time (as is observed in many of the Neotropical primates under consideration).

NY Times Article on COMT Gene

Why Can Some Kids Handle Pressure While Others Fall Apart?
The New York Times ran an article a few days ago about why some students succeed in stressful situations (ie standardized tests) and why others fall apart with worries and anxieties.  This division has been traced back to two different alleles for the COMT gene.  This gene produces the enzyme to clear dopamine from the prefrontal cortex to allow our brain to think, plan, make decisions, and anticipate consequences clearly.  There are two variants, one clears dopamine slowly while the other clears it rapidly.  In a non-stressed environment, test subjects with the slow removing enzymes performed better, indicating that a little stress can provide a cognitive advantage.  However, when 779 Taiwan students, having recently completed the Basic Competency Test (a high stakes placement exam), were tested for the variant, the data showed a very different result.  Students with the slow removing enzyme scored 8& lower than the students with fast acting genes.  In a more stressful environment, the slow removing enzymes were overwhelmed with dopamine in the prefrontal cortex and unable to remove enough.  This led to the students with these slow removing enzymes (nicknamed Worriers) becoming stressed, worried, anxious, and in the end, not performing as well as the students with rapid removing enzymes (nicknamed Warriors).  The article goes on to explain new attitudes to short term stress after studies found that professionals use stress in a more positive, energizing manner than amateurs.  I found it most interesting that students could actually be taught to see stress as beneficial, and thereby score higher on exams.  

Social Effects via Olfactory Sensory Stimuli

Social Effects via Olfactory Sensory Stimuli on Reproductive Function and Dysfunction in Cooperative Breeding Marmosets and Tamarins
This article describes how marmosets and tamarins rely on their olfactory sensory processing to interact and identify with family members.  This study investigates the effects of odor cues on the reproductive systems of these species and how the offspring use odors to ensure their basic needs are met by their parents, which is critical because these species live in a cooperative family environment.  Their high reproductive rate requires all family members to aid in infant care, as mothers may be pregnant or lactating while other infants are still dependent on them.  They have therefore formed social bonds between family members based upon odor cues.  I found it to be a very interesting read considering what we have learned so far about differing reproductive success and social groupings.

Female Hierarchies and Digit Ratios

Hello ANTH 420,

All of our papers this week focused on male hierarchies, mating success, etc. I thought that this article about "Digit Ratios and Dominance in Female Baboons" could provide an interesting, complementary perspective on this topic. As was mentioned in one of our readings, males tend to form hierarchies to maximize their access to breeding opportunities. Females tend to form hierarchies to maximize their access to resources. In this paper, low 2D:4D ratios (which are associated with high prenatal androgen effects)  were found to be associated with high-ranking females. 

-Abi 

Chinese Tree Shrew Genome

Last week we discussed how many genomes have been sequenced but stitched together or annotated. Yesterday an annotated genome of the Chinese Tree Shrew was discussed in this paper.  This genome is interesting because the shrew is closely related to primates and is being considered as an alternative to primate species in biomedical research.  The researchers identified several biological pathways shared between the tree shrew and humans, indicating that it could be useful both for medical research and also for comparative and evolutionary biological research.

Pot Luck 2/06: Primate Immune System Differences

Primate immune system differences identified

This article discusses the findings of a study of the functional differences of genes associated with the immune system between primates and humans. It argues that the results have showed that human and more susceptible to various diseases such as HIV and hepatitis B. The 'core response' between the two species was shown to be the same but the genes that respond to certain diseases has difference responses between primates and humans. Regarding HIV/AIDS specifically, it shows that chimpanzees have a better ability to resist the virus than humans do. Focusing on this disease I found this article interesting because I wonder if it shows the future for humans to naturally become immune or become more resistant to the disease as well. Since the disease is know to have originated in primates, would it make sense they since the disease has existed for a longer period time within their species, they have have a longer time to adapt have through some form of adaptation or evolution or natural selection have been able to fight the disease. Because of the similarities between the initial 'core' immune systems between chimps and humans could it be possible that as time goes on that humans too could form this resistance to the disease. From this example could it be possible that, because primates have been around longer than humans, we could learn more about the future of human evolution especially in terms of responses to disease from the evolution of primates?

ANTH420: Pot-luck --> Human Pheromone TShirt Experiment

Whenever I think about reproductive strategies for a class I think about this kind of experiment.  I am not sure if any concrete conclusions have been made about the effect of pheromones in human mate selection but it's an intriguing possibility to think about.

http://www.pbs.org/wgbh/evolution/library/01/6/l_016_08.html

Potluck -- Genomics and Mental Illness

In light of our discussion last week about the utility of GWAS in developing treatment therapy for mental illnesses (among other clinical presentations), I thought the following article might be an interesting example of how GWAS and association studies in general can be useful in teasing out the differences between the physiological manifestations of certain clinical definitions of mental disorder.

http://www.sciencedirect.com/science/article/pii/S0165178110003094

While it is important to note that mental disorders constitute a much less 'cut and dry' category for which genomics research might be useful than many other areas of primate ecology, this article is a compelling example of how genomics can inform our understanding of pathophysiology and play an integral part in the fine tuning of pharmacological regimens for people suffering from mental conditions that often seem very difficult to pin down or effectively and wisely treat.

Prolonged Menopause in Killer Whales

In addition to humans, orcas are one of the only other species known to have a prolonged period during which they cannot reproduce.  A recent study in the journal Science reveals that the purpose of menopause in killer whales may be to ensure that females are able to care for their sons and guarantee that their genes are passed down to the next generation.  By investing more in their offspring, the females are able to improve their reproductive success.

Proc. of the Royal Soc. B -- Primate UV Spectrum Detection

Certain primates and other mammals have demonstrated the ability to push the boundaries of the detection of wavelengths of light beyond the V and into the UV range. This article:

http://rspb.royalsocietypublishing.org/content/279/1727/387.full.pdf+html?sid=ae2c449a-5f45-40f3-9bbc-bb94572d7f35 (see links on right side of page for PDF access)

explores the specific mechanism for spectral tuning in primates using the aye-aye as a case study and determines that primates undergo spectral tuning at a site distinct from the one correlated with spectral tuning in most other mammals. This finding does not preclude the possibility of similar deep evolutionary origins of similar spectral tuning mechanisms across primates and mammals but has interesting implications for the comparatively recent evolutionary history of primate spectral tuning.

This Week in Science

This was a slow week in Science for primate genomics, but there was one article.

HERE

Chimp research is being scaled back for ethical issues.  What are the implications for primate research?

Seminal Protein Evolution Paper for Potluck

paper
This paper shows the differences in the genes encoding seminal proteins in the different apes.  This project looked at mutational rates and differences in the genes themselves in order to determine the mating behaviors of the most recent common ancestor species as well as selection pressures on the different ape species in terms of sperm competition.

"Owl monkeys who stay true reproduce more than those with multiple partners"

This study was of an owl-monkey population in Argentina done by an Anthropology Professor at UPenn.  Owl-monkeys are relatively monogamous mammals, and they showed that when an owl monkey pair is broken by an intruding individual, the mate who takes up with a new partner produces fewer offspring than a monkey who stays with its original partner.  I found this article interesting because it might explain how human behavior of monogamy developed.

http://www.eurekalert.org/pub_releases/2013-01/uop-omw011813.php

Michael Cruciger