Biomedical research conducted in the last decade has impressed upon society that mental illnesses such as schizophrenia, alcohol dependence and major depression can have genetic bases. Unfortunately, the public’s scientific knowledge has not necessarily translated into social acceptance.

“The landscape surrounding mental illness has changed a great deal over the last decade. Support for medical treatment has grown, but tolerance for the mentally ill … remains low.”

University of Pennsylvania sociologist Jason Schnittker came to that conclusion after comparing the results of nationwide surveys given in 1996 and 2006, looking at the data provided by 1,400 respondents in each case on the public perception of mentally ill people.

His work was published online earlier this month in the journal Social Science and Medicine.

The General Social Survey tracks social and demographic trends and is conducted every other year. Schnittker chose to study the results of the mental health sections of the survey only.

The respondents were presented with three short stories, each involving a person described as having schizophrenia, alcohol dependence or major depression — though the survey did not identify them as such. After reading about the characters, the respondents were asked how likely they thought each person’s mental illness was to be caused by reasons ranging from environmental factors such as stress, to a genetic problem, to God’s will.

The results suggest that genetic associations for these conditions lead to increased support for medical treatments, but have little positive effect on respondents’ tolerance for the mentally ill.

For example, Schnittker found respondents strongly supported medical treatment for the character with schizophrenia, even to the point of legally requiring it, in part because their increased understanding of the illness as genetically based was correlated with their perception of schizophrenics as dangerous. On the other hand, survey respondents did react react somewhat more favorably toward the character with depression in 2006 compared to 1996, and were more socially accepting.

“In this case,” Schnittker wrote, “depression is no longer seen as a sign of personal weakness, but rather is seen as a disease to be nurtured, treated and perhaps accepted as natural.”

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The opening bars of “Who are You” crash through the speakers, the credits roll and the lead actors of “CSI” pull up at the crime scene to investigate yet another murder.

Since “CSI” premiered in 2000, the show, its spin-offs and imitators have hammered home the idea that a person’s genetic material can readily establish his or her presence at a crime scene. The programs’ popularity has even led to the “CSI effect,” where real juries have come to expect that such information is part of the evidence provided at all trials.

But reality is rarely as simple as TV. According to the President’s DNA Initiative, DNA labs across the country saw a 73% increase in their casework from 1997 to 2000, while their backlog was nearly double that figure. One contributor to lab backlogs: samples containing more than one source of DNA. Picking out each individual from such mixed samples can be extraordinarily costly and time-consuming.

Researchers from the Translational Genomics Research Institute (TGen) and the University of California at Los Angeles have developed a new way to detect whether a specific individual’s DNA is part of a mixed sample, even when that person’s genetic material makes up as little as one one-thousandth of the total. As detailed in PLoS Genetics, this method developed by Nils Homer and his colleagues could help forensic investigators determine just who was at a crime scene.

“By employing the powers of genomic technology, it is now possible to know with near certainty that a particular individual was at a particular location,” TGen researcher and study author David Craig said in a statement. “Even with only trace amounts of DNA and even if dozens or even hundreds of others were there, too.”

The researchers used high-density SNP arrays, much like those used by 23andMe, to genotype a specific individual, a DNA mixture, and a reference DNA sample. They then used statistical methods to compare the individual to both the DNA mixture under investigation and the reference sample. These statistics allowed them to determine if a person had in fact contributed to the DNA mixture.

The researchers demonstrated the utility of their method by testing it on DNA mixtures composed of anywhere from two to 200 people of Caucasian ethnicity, with each single person contributing as little as one-tenth of a percent of the total sample material.

“It opens up a whole new can of worms of what’s possible to do forensically,” said Stanley Nelson, a UCLA-based co-author of the study (and 23andMe advisor), in a statement. (23andMe was not associated with this research.

The ability to distinguish an individual’s DNA from a mixture also has implications for genome-wide association studies. Such projects require large quantities of genetic information, and genotyping the thousands of individuals participating is a costly process. When researchers try to make the data publicly available for use in other studies, they often pool the information in order to maintain each individual participant’s confidentiality. Homer and his colleagues argue that their technique for picking one individual’s DNA out of a crowd could strip away that pretense of anonymity.

“Our findings make it very clear that such an approach realistically does not conceal identity,” they wrote in their study, suggesting that researchers should confidentially share their data in its entirety instead.

Image from the National Forensic Science Technology Center

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In the current issue of Nature Genetics though, Massachusetts Institute of Technology-based researcher Robert Hoffman argues that scientists who write for wikis aren’t getting due credit for their work. While wikis like the one Huss and his colleagues have on Wikipedia are useful, he says, the individual contributions must be recognized.

In other words, contrary to the old adage, there does need to be an “I” in “Team”, especially when working in wikis.

Hoffman’s solution is to launch yet another gene wiki, this one creatively named WikiGenes. Unlike most wikis though, this one comes with the ability to attribute every line written to its author.

A scientist’s life isn’t just about satisfying curiosity and collaborating with others, says Hoffman in his commentary. Rather, it’s about “recognition by others, which translates to employment, grants, and ultimately, the privilege of being a scientist.” (See the recent post by 23andMe director Esther Dyson for another take on the significance of personal interest in science.)

To make sure each contributor gets his due, Hoffman’s WikiGenes has something called “authorship tracking technology.”  The software allows readers who like a particular line or phrase on one of the WikiGenes pages for, say, BRCA1, to identify the author and correctly attribute the quote to him or her. Theoretically this is also possible on Wikipedia, but there the authors are listed in the change log, which appears under a separate tab.

There are a few other differences between the Wikipedia-based gene wiki and WikiGenes.

Editing the WikiGenes site is fairly intuitive, which is good for first-time collaborators. Instead of having to go to the edit tab as on Wikipedia, WikiGenes has an “Edit this Page” option at the upper right corner of the page that allows registered users to make and save changes.

WikiGenes also has a demo account option where people can sign up and play with edit the content, though only changes made by registered users will appear on the site. This is probably a good thing; you wouldn’t want someone to edit the page on a gene as clinically important as BRCA1, for example, without having to sign their name to it. Still, it is a wiki and therefore an open-access and editable collaboration.

Perhaps the most glaring difference between Hoffman’s WikiGenes site and Huff et al’s gene wiki, however, is that the format isn’t as easy on the eyes  the WikiGenes entries don’t have colorful graphics to break up the text. Perhaps Lewis Carroll said it best at the beginning of Alice’s Adventures in Wonderland : “Once or twice she had peeped into the book her sister was reading, but it had no pictures or conversations in it, ‘and what is the use of a book,’ thought Alice, `without pictures or conversation?’”

Photo credit: WikiGenes.org

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The daily rigors of tying and untying would soon render our shoelaces frayed and useless if it weren’t for those protective plastic aglets on the ends. Roughly the same situation exists for the chromosomes in your cells. Without protective pieces of DNA on their ends called “telomeres”, repeated rounds of DNA copying would lead to chromosomal breakdown.

The cellular machinery that replicates DNA before cells divide isn’t able to make it to the very end of chromosomes. If it weren’t for the disposable buffer created by the thousands of repetitive DNA base pairs that make up telomeres, critical bits of genetic information would be lost with every cell division.

This protection only can last only so long, however. After 50 or so generations, a cell’s telomeres get so short that they can no longer maintain the genome’s integrity, signaling the end of the line for the cell.

Studies have shown that the “normal” telomere length varies from person to person, but is genetically influenced . In the August 15 issue of Human Molecular Genetics, Massimo Mangino and his colleagues from the University of Leicester identify a gene variant that could play a role in determining telomere length among people with European ancestry.

The researchers found that people with the C version of rs2630578 have telomeres in their white blood cells that are between 400 and 800 base pairs shorter than people with two copies of the other version of this SNP. The authors estimate that this is the equivalent of having cells that are comparatively about 15 to 20 years older, though no actual effects on aging or health were associated with this SNP in the study.

(While rs2630578 is not in 23andMe’s database, customers can check their data using the direct substitute rs2668301. The T version of rs2668301 is equivalent to having the C version of rs2630578.)

SNP rs2630578 lies in the BICD1 gene, which is part of a cellular pathway regulating protein movements throughout the cell. Studies in yeast have found associations between transport genes like BICD1 and shorter telomeres, but this is the first time such a link has been seen in human studies.

Mangino and his colleagues found that the C version of rs2630578 decreased the amount of BICD1 protein made by cells, which they theorize might affect telomere length. Having either one or two Cs at this SNP seemed to have about the same effect on BICD1 levels, indicating that having two copies of this SNP version might not be any worse than having only one.

As the first study to associate a SNP with telomere length, further work is needed to confirm these findings — and to see if the same SNP might be involved in conditions where shorter telomeres are known to be a factor, such as premature aging syndromes and cancer.

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Tobacco use is the leading cause of preventable deaths in the United States — every year it kills nearly 440,000 Americans.

While about 70 percent of the 45 million Americans who currently smoke have said they want to quit, the Centers for Disease Control and Prevention estimates that only about 10 percent of them will succeed, due in large part to the addictive qualities of the active ingredient in tobacco, nicotine.

Researchers have been looking at the genetic basis of nicotine dependence, characterized by tolerance to the drug and the presence of withdrawal symptoms in its absence, with the long-term goals of better assessing a person’s risk for addiction and potentially developing targeted treatments.

Last year, Laura Bierut and her colleagues at the Washington University School of Medicine identified a single variant in a nicotine receptor that increases a person’s risk of developing nicotine dependence. A later study indicated the same SNP can actually reduce the risk of developing cocaine dependence. And now a study published this month by Bierut and her colleagues shows that the variant also influences how much pleasure a first-time smoker will experience from the first puff of a cigarette.

“The type of variant you have at this particular receptor — the alpha-5 nicotinic receptor — may actually predict whether or not you will do well on nicotine replacement therapy,” Bierut said in a statement at the time.

The version of SNP rs16969968 that can increase the risk for nicotine addiction is found at appreciable levels only in European populations. People with two copies of the less common A version of the SNP are twice as likely to develop nicotine dependence when exposed to smoking than people with two copies of the more common G version.

(This SNP isn’t in 23andMe’s database, but we do have data on an equivalent SNP: rs1051730, which has also been linked to nicotine dependence in European populations, as The Spittoon previously mentioned here. As with rs16969968, the rarer A version of rs1051730 is associated with increased nicotine dependence compared to the more common G version. Though both SNPs have the same effect on nicotine dependence, the size of the effect caused by rs1051730 may be slightly larger or smaller compared to the SNP Bierut and her colleagues study.)

A new study from Bierut’s group published this month in the journal Addiction shows that the same version of rs16969968 previously associated with nicotine dependence is also linked to the pleasurable rush some first-time smokers get. Each A at rs16969968 increased a person’s odds of having found that first puff pleasurable by 1.6 times compared to people with no copies of an A. This “buzz” was in turn associated with an 8-fold increase in odds of being a current smoker.

“The finding of a genetic association with pleasurable early smoking experiences may help explain how people get addicted — and, of course, once addicted, many will keep smoking for the rest of their lives,” said the study’s senior author Ovide Pomerleau in a statement.

“It appears that for people who have a certain genetic makeup, the initial physical reaction to smoking can play a significant role in determining what happens next. If cigarette smoking is sustained, nicotine addiction can occur in a few days to a few months.”

Bierut’s research on SNP rs16969968 also extends to addictive substances other than nicotine. Back in June, her group released a study that examined cocaine addicts and non-drug abusing controls to show that having the nicotine dependence-predisposing A version of this SNP actually decreases the risk for cocaine dependence. Having one A decreases the odds of cocaine dependence risk by about 33 percent; two copies decrease the odds by about 45 percent.

The involvement of this SNP in both nicotine and cocaine addiction, and its opposing effects, may seem perplexing. But Bierut and her colleagues suggest that the answer lies in how each addictive substance affects dopamine in the brain’s reward pathway – a key player in the pleasurable feelings produced by drugs that can lead to addiction.

Nicotine triggers the release of dopamine, a neurotransmitter that activates pleasure pathways in the brain. In contrast, cocaine produces pleasurable feelings by preventing the dopamine that is naturally released in the brain from being reabsorbed when its job is done. Excess dopamine hangs around in the brain and produces the “high” associated with the drug.

The nicotine receptor that rs16969968 affects is involved in normal dopamine release, even in the absence of nicotine. So when the A version of this SNP dials down the receptor’s activity, natural dopamine release is reduced. This means there is less dopamine available for cocaine to keep around in the brain, and the amount of pleasure the drug can induce is diminished, possibly enough to keep a person from getting addicted.

Image from FreeDigitalPhotos.net

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A new paper by Venter and colleagues at his Rockville, Maryland-based institute provides a prime example. Writing in the September issue of Clinical Phamacology & Therapeutics, Venter et al. argue that knowing how genetic differences between ethnicities affect patients’ reactions to certain medications isn’t good enough. To make sure patients get the best healthcare, they say, doctors should be looking at how each person is likely to respond to a particular drug regimen based on his or her unique genetic makeup.

“Even the term ‘Caucasian’ can be deceptive,” the authors noted. “If a self-identified Caucasian originates from a founder population in which certain disease-specific alleles occur at higher frequencies (e.g. Quebec French Canadians or Ashkenazi Jews), his or her doctor may miss an important aspect of the patient’s medical history. One’s ethnicity/race is, at best, a probabilistic guess at one’s true genetic makeup.”

To further emphasize the differences between people within the same ethnic group, the authors compare the publicly available genome sequences of Venter himself and Nobel Prize winner James Watson, focusing on six genes involved in drug metabolism.

One of those genes revealed a substantial difference between the two men. CYP2D6 is involved in the metabolism of various drugs for high blood pressure, heart arrhythmia and depression. Venter’s genotype indicates that like most Europeans he is an “extensive metabolizer” of such drugs; but Watson’s genotype puts him in the “intermediate metabolizer” category, which is more common among Asians.

Using race as a guide, the authors noted, a physician would have no reason to expect Venter and Watson to react differently to drugs that are metabolized by CYP2D6.

Venter and his colleagues conclude by emphasizing the need for personalized health care based on genomic information, adding that the cost to do so is dropping rapidly.

“Given the complex nature of drug responses, it would ultimately better serve all to dissect the relevant factors of a drug response instead of categorically stereotyping a culture with a presumed genetic background.”

Images: Venter photo by Michael Janich; Watson photo courtesy of the National Library of Medicine

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Despite CNET’s assertion last week that Bigfoot couldn’t possibly be a hoax because people always bring their A game to Palo Alto, the carcass in the ice has turned out to be a rubber gorilla suit. And the freezer wasn’t that big either.

Sorry, Bigfoot believers, this means the DNA evidence presented at last week’s press conference almost certainly came from one or more non-Bigfoot sources, and probably not from a Giant Bipedal Possum of northern Georgia either.

With websites around the world gleefully spreading the news, it’s perhaps best to let professional Bigfoot hunter Tom Biscardi — who arranged last week’s Palo Alto press extravaganza — speak for himself. But as it seems Biscardi wasn’t present at The Thawing, he’s deferred the task to someone else.

Here then is part of the eyewitness account from Tom Kulls of SquatchDetective.com, as posted on Biscardi’s site:

“On August 17th, 2008 Searching for Bigfoot Team Director of Field Operations, TJ Biscardi [Tom's son] and myself, were up early to discover that some hair was now exposed. I extracted some from the alleged corpse and examined it and had some concerns. Bob Schmalzbach arrived and concurred. We burned said sample and said hair sample melted into a ball uncharacteristic of hair.

At that time we contacted Mr. Biscardi who gave us permission to begin an expedited melting process. We set up a salamander [portable] heater to heat the freezer. Within one hour we were able to see the partially exposed head, as I was now able to touch it, I was able to feel that it seemed mostly firm, but unusually hollow in one small section. This was yet another ominous sign. Within the next hour of thaw, a break appeared up near the feet area. As the team and I began examining this area near the feet, I observed the foot which looked unnatural, reached in and confirmed it was a rubber foot.”

Science in action.

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This is her account …

Bigfoot empresario Tom Biscardi held up a printed email that he said contained DNA results from the tall, hairy carcass that Matt Whitton and Rick Dyer found two months ago in Georgia.

“Bottom line,” he told the reporters and Bigfoot enthusiasts who assembled in a Silicon Valley hotel ballroom on Friday, “one of [the three samples] came back and it was messed up, inconclusive. One came back as human. And the other one came back that because where they took the sample  which was from the intestines, ok?  it came back possum, so that may be possibly what this thing had eaten. We don’t know.”

With those words, Biscardi’s much-publicized press conference in Palo Alto’s Crowne Hotel turned from confirmation of Bigfoot’s existence into, well, anything but. But it sure was fun. Consider this exchange between reporters and the discoverers of the alleged Sasquatch:

Media: So you’re just keeping it in a freezer – that’s it?
Dyer: Well not now.
Media: How big is the freezer?
Dyer: It’s big.
Media: It’s been on ice for two months?…. When was the picture taken that we’ve seen on the net?
Dyer: When the freezer was being filled up with water.
Media: Why’d you fill up the freezer with water?
Dyer: To put it in a block of ice.
Biscardi: That’s what I asked also. I said why would you put water in there? He said, “Well, that’s how you make ice.” I said, “No, it freezes the way it is.”… But they just kept dumping the water in.

Both Whitton and Dyer wore beige caps emblazoned with the words “Searching for Bigfoot,” the name of Biscardi’s Menlo Park, Calif., company. Both men appeared slightly uncomfortable. Maybe that’s because of the death threats they claim to have received since going public with the discovery.

“It seems to be that way in the Bigfoot world, that there are a lot of people that may be little delusional, and they may be a little jealous too,” Whitton noted.

The men declined to reveal the exact location of their discovery, citing their concern for still-living members of the species. The next step, Biscardi says, is to go back and do research on Bigfoots in the wild by capturing one.

“We’re not saying we’re gonna keep it in captivity. We’re gonna keep it, study it, put a tracker on it, send it back to the protected area – that’s what the real purpose of this whole thing is,” he said.

Sadly, the Bigfoot carcass itself was not present at the conference. Whitton and Dyer say they’ve turned it over to Biscardi, who’s apparently promised the first viewing rights to Fox News’ Megyn Kelly.

“When can we expect results of the [carcass'] autopsy?” a reporter asked.

“Tom Biscardi’s contacted lot of people in the scientific world. I don’t know them by name but we’re gonna have top-name scientists,” Whitton replied.

Biscardi hinted that Richard Klein, a Stanford professor of anthropological sciences would be on his Bigfoot “Dream Team.” And he offered a somewhat cryptic explanation for why he hadn’t asked anthropology professor and well-known Bigfoot researcher Jeff Meldrum to join the effort.

“In my opinion,” he said, “Jeff Meldrum is an associated anthropologist, not a true anthropologist that can really do what we need.”

One thing somebody needs to do is explain the creature’s unusual dentition, which was the subject of another inconclusive exchange with the media:

Media: So how many teeth are in that picture? It looks to me like six incisors.
Biscardi: There are exactly six.
Media: And you’re telling us that a primate has six incisors?
Biscardi: I’m not telling you that. I’m not the scientist. I’m telling you what the picture shows.

Then Biscardi showed a photo of a live Bigfoot in the woods, explaining that it was better than other photos because it wasn’t blurred. “You’re actually seeing a bipedal creature covered with hair,” he said. “You can actually see his ear, its nose and its eyes also.”

“Is this a hoax?” a reporter called out toward the end of the conference.

“This is as real as you’re standing right where you are sir,” Biscardi replied.

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In the movie Batman Begins, young Bruce Wayne attends the opera with his parents and becomes increasingly uncomfortable at the costumes that remind him of the bats he had encountered earlier that day.

German and American scientists have now found that the gene variant rs4680 is associated with regulating such anxious reactions to emotional images.

With more research, study co-author Christian Montag noted in a statement, “it might be possible to prescribe the right dose of the right drug, relative to genetic makeup, to treat anxiety disorders.”

For the study, which appears online August 10 in the journal Behavioral Neuroscience, researchers measured the startle responses — blinking in reaction to unexpected loud noise — of 96 German women as they viewed various images. Each woman was shown happy images such as those of animals or family; threatening or fear-inducing images such as those of injured people or weapons; and emotionally neutral images like a hair dryer or power outlet. A few seconds after each image appeared, researchers randomly startled the women with short, loud blasts of white noise and recorded the their startle responses.

The researchers found when viewing unpleasant pictures, the startle response of women with an A at both copies of rs4680 was about six times stronger compared to those with only one A or none at all.

“This single gene variation is potentially only one of many factors influencing such a complex trait as anxiety,” said Montag in a statement. “Still, to identify the first candidates for genes associated with an anxiety-prone personality is a step in the right direction.”

The SNP is in the COMT gene, which is involved in regulating the “feel-good” hormone dopamine. It has also been linked with breast cancer risk — Asian-American women who have an A at one or both copies of rs4680 and also drink black or green tea appear to have a decreased chance of developing the disease. People with an A in both copies of rs4680 have been shown to break down dopamine less efficiently. Studies have also correlated the variant with behaviors such as obsessive-compulsive disorder.

The researchers think the stronger reaction to unpleasant images by people with two copies of the A version of rs4680 might be due to increased dopamine levels in some parts of the brain.

“Elevated dopamine in the prefrontal cortex could result in an inflexible attentional focus on aversive stimuli,” Montag and his colleagues wrote.

That’s a fancy way of saying that people with elevated dopamine in that part of the brain are more prone to respond like a deer in the headlights when faced with a potential threat. In their paper, the research suggest that evolution has created a trade-off. The A version of rs4680 appears to boost working memory and cognitive function compared to G — but it also hampers emotional control. Plus, being unable to take one’s eyes away from something unpleasant could be dangerous, especially if people stop paying attention to their surroundings.

Maybe that’s why Bruce Wayne chose to become a bat; having criminals momentarily distracted at the sight of something scary and terrifying might give him a valuable edge.

Image from: Don Pfitzer, US Fish and Wildlife Service

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Dogs suffer from a number of inherited eye conditions; the progression of their symptoms and gradual vision loss have been found to mirror various similar disorders in humans. One example: cone-rod dystrophies, which rob humans and dogs of their vision by destroying both the cone cells that pick out images and colors in bright light and the rod cells, which work best under low lighting conditions.

Norwegian and Swedish researchers have used a genome-wide approach to identify a genetic mutation in standard wire-haired dachsunds that is responsible for early onset cone-rod dystrophy, known as CRD. Their results, published online today in the journal Genome Research, could help researchers studying similar cone-rod disorders in humans to find the genetic basis of those conditions. About one person in 40,000 is affected by a form of cone-rod dystrophy.

The team used a family of dachshunds, several of whom had CRD. Lingaas and his colleagues used a genome-wide analysis approach on 26 full- and half-siblings, studying nearly 50,000 gene variants much the same way 23andMe uses an array of gene variants to analyze customer DNA. They studied the dogs in sibling pairs — where one litter mate had CRD and the other had normal vision — to find out what genetic differences might be responsible for the eye condition.

The researchers narrowed their focus to four candidate genes, and ultimately identified a deletion in part of the NPHP4 gene as the cause of the dogs’ blindness.

“This [NPHP4] gene has been associated with a combination of kidney and eye disease in human patients,” said lead researcher Frode Lingaas in a statement. “Here, we found a mutation that affects only the eyes, suggesting that this gene might be a candidate for human patients with eye disease only.”

Gene therapy treatments based on other associations have already been tried in dogs with cone-rod dystrophies. Researchers hope such treatments could some day be applied to similar conditions in humans.

“Assuming that NPHP4 has the same function in humans and dogs,” Lingaas and his colleagues added in their paper, “it will now be interesting to search for mutations in NPHP4 in human CRD patients without kidney disease.”

Image from: Frode Lingaas, Norwegian School of Veterinary Science

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