Rubbing Up the Gene Genie

Gene Genie Logo by Ricardo Vidal at My Biotech LifeSciencebase is this week proud to play host to the Gene Genie Blog Carnival thanks to an offer from Bertalan “Berci” Meskó over on the excellent ScienceRoll. For those who don’t already know, a Blog Carnival doesn’t usually involve a lot of be-costumed revellers dancing through the streets to the sound of the samba band, but is a gathering of like-minded bloggers brought together through the power of the tubular Interwebs to share their latest posts on a given subject.

The Gene Genie carnival has an obvious theme. No, it’s not the songs of aging but outlandish popster David Bowie. No, it’s not the magical character of Arabian Nights entombed in a lamp, and no it’s nothing to do with quasi-sci-fi-retro-fit BBC cop show Ashes to Ashes. It’s about genes. See, I told you it was obvious.

Anyway, the carnival (from the Latin carnis, meaning meat, and levare, to put away) covers some of the hot topics in the world of genes, genetics, DNA and all things inherited.

So, here we go:

  • Gene Found for Ghosal Hematodiaphyseal Dysplasia Syndrome: A Rare Syndrome with Increased Bone Density (DNA And You)
  • Home DNA tests on the up, ‘safer’ clinic DNA tests on the down (Genetics and Health)
  • Gene Plays a Role in Hair Loss Identified (The Biotech Weblog)
  • Extinction Fears of the Red-Headed Homo Sapien (GNIF Brain Blogger)
  • Where are brown people short? and Shadows of the Past in Genes (Gene Expression)
  • Genetics Cause of Smell Perception (ArticleBiz.com)
  • Why do we have common risk variants for metabolic diseases? (Genetic Future)
  • Researchers Discuss MEGF10 Gene Assocation To Schizophrenia (Scientificblogging)
  • Differences of gene expression between human populations (Anthropology)
  • Brain scan reveals cultural differences (Sciencebase)
  • Scientists Link Gene That Promotes Long Lifespan to Cholesterol (Biosingularity)

In the realm of personalized genetics:

  • NY Times: Insurance Fears and DNA Testing (DNA Direct Talk)
  • Ann Turner on Personal Genomics Companies 23andMe vs deCODEme and deCODE Launches PrCa Prostate Cancer DNA Test (Eye on DNA)
  • One Fifth of GDP! (Gene Sherpas)
  • Why should you get a free 23andme test? (bbgm)
  • 23andMe Adds Paternal Ancestry and an Updated Gene Journal (Genetic Genealogist)
  • New York Times: Genetics and insurance (Tracing the Tribe)
  • SNPwatch: One SNP Makes Your Brown Eyes Blue (Spittoon)
  • Global Awakening in Genetic Counseling (Scienceroll)
  • Your Future IS Your Genes: Diagnosing Bipolar Disorder from a Blood Sample (Living the Scientific Life)

    Genetic Futre ThumbnailThe next edition of Gene Genie will be hosted by DNA Direct Talk, watch out for it! For more information about the Carnival here.

Don’t Poison Your Dog This Holiday

Theobromine structure

‘Twas the night before Christmas, when all through the house
Not a creature was stirring, not even a mouse

Well, that may not be quite true, do you know what your dog is doing right now? What about the cat? They’re not rummaging through the presents under the tree are they? You didn’t leave any luxury plain or dark chocolates under there did you? If you did, you could wake up to a quite horrible surprise when Christmas morning comes around. Chocolate makes pets ill! That’s the important seasonal warning being delivered by vets everywhere.

Poisonous chocolatesSo, what’s the problem? Surely a little chocolate snack in the night isn’t going to harm good-old Fido? Well, our vet begs to differ and so do the veterinary toxicology sheets for the chocoholics’ favourite fast-food. Man’s best friend, and several other animals, you see lack a particular liver enzyme that their owners do possess, that breaks down a toxin found naturally in chocolate – theobromine.

Theobromine has nothing to do with the element bromine, rather it is a bitter alkaloid from the seed of the cacao tree, known scientifically as Theobroma. The basic chemical skeleton is a xanthine unit, same one on which several other more well-known natural chemicals are based. The stimulant caffeine (from coffee beans) is a xanthine, for instance, so too is theophylline (found in tea and used in treating COPD and asthma).

Non-chocolate Labrador

Lacking the enzymes to metabolize theobromine leaves dogs exposed to the toxic action of the compound, which can cause vomiting, diarrhoea, hyperactivity, tremors, seizures, abnormal heart rhythms, and in extreme cases death.

So, what are the first signs of chocolate poisoning, what’s the lethal toxic dose, and what should you do if you think your dog has been at the chocolatier’s produce? Well, the first signs of chocolate poisoning are vomiting and diarrhoea, increased frequency of urination, and nausea. A toxic dose that will cause symptoms is about 100-150 milligrams of theobromine per kilogram of body weight, toxic dose could be approximately 250 and 500 mg/kg. A kilogram of milk chocolate will contain about 2 grams of theobromine. So a greedy, little dog is at greater risk of a serious digestive upset than a big gluttonous dog if he or she snaffles a 250 g bar of milk chocolate.

There is no direct way to treat chocolate poisoning in dogs, although inducing vomiting if the animal is caught “brown-pawed” (best left to the vet) is probably a good idea. A dog that has eaten a lot of chocolate will almost certainly require hospitalisation for at least the four days while the theobromine is naturally excreted (It takes about 17 hours for a dog to excrete half of the theobromine in its system, which means this toxin will reach vital organs repeatedly via the blood stream). But, who needs that, or worse, at Christmas? As they say: a gram of prevention is worth a kilo of cure.

For lovers of cats (small, domestic, big, wild) keep the aspirin out of reach. It’s deadly poisonous to felines.

Male Semen is Redundant

Male sperm

You’ve seen the kind of thing: “Warehouse Razed to the Ground in Fire”, as if razing didn’t already mean the building was levelled. Worse, “Balloon Ascends Up into the Air”, ascending down is very difficult, simultaneously, at the same time, if not impossible; so too is descending up.

However, the award for the most redundantly tautological headline of the year has to go to Scientific American for Male Semen Makes HIV More Potent, that’s male semen as opposed to the female variety, is it? It’s an important discovery, nevertheless that a chemical constituent of semen affects the immune system facilitating viral infection.

Scientific American is probably not the first and original nor the ultimate and last publication to use this phrase though. DoctorNDTV ran a story with the title: Male semen loss concerns and risky sexual behaviour. Then there’s a research paper in the Journal of Avian Biology that discusses bacteria found in the “male semen” of red-winged blackbirds. Even the venerable and well-respected New Scientist recently published an item on insect courtship and egg laying. Apparently, the trigger for egg laying “is a small protein called sex peptide (SP) in the male’s semen.” Again, the word male, while perhaps making the sentence smoother, is totally redundant and not needed.

A search for the phrase “male semen” on PubMed produced not hits, although “male sperm” came up several times in various journals. So as not to appear sexist, I also did the equivalent searches for “female semen” and “female sperm” and quite surprisingly got several PubMed hits. One paper on mythology mentions how at one time in human history a godly being or other supernatural entity was thought to intervene in the merging of male and female semen to bring about conception. Not quite a modern biomedical reference point, then. The phrase “female sperm” gave absolutely no hits, unsurprisingly.

Maybe the clue as to why these various publications qualify the word semen lies in those papers discussing the mythology of reproduction. A quick Google shows that there are many references to religious and proto-religious texts that discuss both male and female semen as if they were both real. Perhaps by qualifying semen as male in modern writing, rather than simply discussing semen, there is some referential nod to humanity’s misconstrued understanding of reproduction. But, modern understanding of reproductive biology defines semen as a product of the male reproductive organs that acts as a transport medium for sperm, so, like I said, it’s redundant.

I asked linguistic guru Steven Pinker of Harvard University, whose book The Stuff of Thought I reviewed on Sciencebase recently, about this apparent paradox. Pinker told me that he suspects that, “the cause is not a nod to the ancients, but a desire to call the reader’s attention to the fact that it’s
the naturally occurring fluid that encourages the potency of the virus, not some externally administered product.

“Semen Makes HIV More Potent implies to me,” he said, “that adding semen increases the potency, rather than that the HIV exploits the properties of the semen it finds itself in.” He adds that it is peculiar that this may be the case. “Odd that the redundancy should do that,” he told me, “but somehow I think it does.”

Intriguingly, after I contacted Pinker, I saw that the journal Nature, as opposed to the popular science magazine, Scientific American, had covered the same story. In Nature, however, their piece was entitled – Semen boosts HIV transmission. So, for some reason they felt semen does not need a masculine qualification of any kind. The tautology of the phrase “male semen” may seem trivial, but it is an important issue.

Googling for Genes

Those clever people at Harvard are using Google‘s API to allow users to search for gene sequence fragments on the Web in combination with a text query. You’re limited to 1000 searches per day and have to enter your own API key to get the maximum benefit. But. that’s probably enough to be going on with.

From the site: Query Gene is distinctive because it is not limited to a single database. Instead it captures genetic information across the net using Google. It works by taking a gene sequence in combination with other search terms, finds similar sequences using NCBI’s MegaBlast, retrieves the descriptions of those matching genes from NCBI’s Entrez Nucleotide database, and performs a series of Google searches using the combination of your original search terms and each gene description. The percent sequence identity is indicated alongside each match: this indicates how much of your queried sequence is contained in the sequence it matches.

You might want to find out what disease states are associated with a specific nucleotide sequence. No problem. Paste in the sequence and enter a text phrase, such as “genetic disease associated with” and up pop the results. Well, actually, they didn’t with the test I tried, but that could be down to my browser configuration. I got “Sorry, we are under maintenance: Please try again in a few weeks”.

A sample sequence is given here. If someone else could confirm or refute the maintanance outage for ChemSpy readers that would be very helpful.

Murine faeces

I’m not sure whether I should admit to the following, but this morning I found little scatterings of murine faeces and could detect a musky yet strong smell of ammonia in the storage area where we keep our dog and cat food. Not nice. In case you haven’t guessed, we got mice.

Odd that these little critters should be so brave as to venture into the part of the house in which the cat spends some of its time and although he is getting on in years, he does still have the legs for a chase (especially when the dog slips her lead and chases him out of the door. Anyway, traps have been bought and placed, droppings have been removed and traces of murine urine have been mopped up (with a cotton bud) and the whole area disinfected.

I got to thinking about that word I used just now. Murine. The “ine” suffix means just means “of”, “like”, or “referring to”, while the “mur” was derived from “mus” then “mur” for mouse in an originating Indo-European language and thence to Latin – “murinus” meaning of mice. The root gives rise to the scientific group name for both mice and rats Muridae or sub-family Murinae. Others words of similar structure include porcine (pigs), bovine (cattle), ursine (bears), ovine (sheep), equine (horses), and of course feline and canine, but not supine.

Shopping for Genes

Leaning strongly towards the bio today, I thought I’d mention a new database for biologists that works like a shopping mall. An international team has opened a virtual bazaar, called PAZAR, which allows biologists to share information about gene regulation through individually managed boutiques. Customers may draw data for free from any boutique or extract information from the “superstores” that aggregate data of similar types.

In deciphering the human genome sequence, researchers hope to understand the “when and where” of gene expression because it could underpin novel cancer therapies, stem cells treatments for degenerative disease, and explain complex diseases such as diabetes.

Male-Female Crabs Split their Difference

Male-Female Crab

David Johnson and Robert Watson thought they had seen all there was to see in the Chesapeake Bay in almost three decades until they pulled out a crab from the way that had a male left half and a female right half. Now, that crab, acquired by Romuald Lipcius of the Virginia Institute of Marine Science at the College of William & Mary, has moved sideways into the world of natural metabolites where its gynandromorphic peculiarities have helped scientists, for the first time, discover that some molecules can be made only by one sex and not the other.

The male-female crab is a unique example of the blue crabs. It turns out that the males of this species produce a natural metabolite that is absent in females. This suggests that some complex biochemistry is underway that is activated only in males. Robert Kleps of the University of Illinois at Chicago and colleagues have isolated this small molecule and identified it as 2-aminoethylphosphonic acid (AEP), an uncommon but well-documented natural metabolite.

We used low-field NMR using phosphorus-31, to observe the small molecule, explains Kleps. He points out that science tends to get lost in the rush for higher field NMR running hydrogen-1 and carbon-13 on 100 kilodalton proteins. However, he adds that, “Even low-field NMR spectroscopists can make interesting discoveries. I’m very happy to have stumbled over this metabolite, while doing basic research on invertebrate metabolism.”

So, why might the existence of a metabolite in the males of this blue crab species and not the females have any bearing on our everyday lives? Well, there are well known differences between the sexes in people, such as disease susceptibility, anatomy and drug metabolism. Kleps points out that these differences might in fact be due to the presence or absence of a crucial metabolite.

Now that the existence of a sex-specific metabolite has been found for one animal the search is on for others, including ones that might exist in people.

For more details on the NMR study check out my column on SpectroscopyNOW.com, the research paper itself is available in Plos One.

You can hear a description of the crab from Lipcius here and listen to Kleps’ podcast

MMR and Statistical Manipulation

Measles virus

When I was still at high school, way back in the late 1970s, there was a health scare that got a lot of media attention. Apparently, there was a perceived risk that the whooping cough vaccine could cause brain damage. The fall off in vaccination for this disease is claimed to have led to the widespread outbreaks of whooping cough in 1979 and 1982, there having previously been almost zero annual cases. At the peak there were some 60,000 cases.

Fast forward to the near present and you will recall similar scare stories about the combined measles-mumps-rubella vaccine, the MMR, and claims by researcher Andrew Wakefield (Lancet, 1998) that MMR could cause autism in some children. It’s a topic guest blogger Michael Marshall covered on Sciencebase in November 2004. It seemed that, at the time, the debate was pretty much over. However, despite repeated demonstrations of the apparent inadequacies of the original research into a link between MMR and autism, the issue is resurrected on a regular basis. Most recently in a cover story in The Observer, which drew much flack, but also left the chattering classes once more in a flap.

Right now, I’m looking at an article from the print edition of The Times offering an answer to the Question of the Week – “Measles or vaccine?” – the article talks of how measles has reappeared and it is apparently all down to many parents’ reluctance to have their children vaccinated with the MMR jab. The article talks of “herd immunity” and how enough children have had a double dose of MMR which should stave off an epidemic. The emergence of herd immunity, of course, will be little comfort for a parent whose child experience any of the potentially severe side-effects of vaccination.

In the article, pictured alongside a blow-up of the measles virus and an image of a nasty-looking hypodermic needle, are two charts, one showing the number of cases of measles in the UK from 1940 to the present day and the other showing the number of deaths over the same period. Incidence of the disease ebbed and flowed during the period up to the early 1970s whereupon cases began to fall rapidly from a peak of 800,000 a year in the early 1960s to just one or two hundred a year by the mid-1970s.

The MMR vaccine was introduced in the US in 1971 and later in the UK, thereafter incidence of measles has pretty much fallen to levels close to zero. It seems that the pre-vaccine drop had another cause, presumably reduced overcrowding, improved nutrition, better hygiene and healthcare. No one knows at what point this fall would have reached a plateau.

In contrast, the second chart of death rates shows an exponential decline in measles deaths since the 1940s, by about 1970 measles deaths were also close to zero. The risk of getting measles is about one in three, assuming no vaccination coverage at all. The risk of serious consequences to this disease, which personally I had in 1972 or thereabouts, is somewhere between 1 in 5000 and 1 in 15,000. Compare that to the risk of death in a road accident. According to Transport2000 , the UK’s national environmental transport body, each of us has a 1 in 17 chance of being killed or seriously injured in a road crash during our lives. Such figures damn the disease statistics somewhat. Of course, vaccination does come with some risks, but adverse reactions, such as seizures with an associated risk of brain damage, exist at the 1 in 10,000 level.

There has been one UK death from measles since 1992 (as opposed to the several hundred each year during the 1940s). The unfortunate victim was apparently suffering an underlying lung disease for which he required long-term immunosuppressant drugs. He was very unfortunate to be exposed to the measles virus, and when he contracted the disease he was very unlikely to have recovered. This is one fatal case. Even with near 100% vaccination, there would still be a finite risk of any random member of the population contracting the disease. Unfortunate, but true. The statistics would not lie surely?

Intellectual genetics

Tug of war

Two worthy legal moratoria – the Agreement on the Trade-Related Aspects of Intellectual Property Rights (TRIPS)
and the Convention on Biological Diversity (CBD) – are potentially in direct conflict when it comes to plant genetic resources and intellectual property rights, at least that is the conclusion of legal expert Megan Bowman. However, potential conflicts could be reconciled in this context by applying the common sense notion of remaining true to the over-arching principle of global welfare-maximisation in TRIPS and by utilising patent exemptions in appropriate circumstances. This, Bowman claims, will allow TRIPS and CBD to operate in a way that achieves both their objectives equally well so that intellectual property rights can be appropriately recognised and biodiversity can be sustained.

Writing in the International Journal of Intellectual Property Management (2007, Vol. 1, pp 277-292), who is a trained barrister and a lecturer in the Law School and Centre of Strategic Economic Studies, at Victoria University, Melbourne, Australia, points out that international recognition of intellectual property rights has grown, particular in the biotech arena, as biodiversity levels have fallen across the globe. Bowman points out that these two trends have become related since the creation of TRIPS and CBD in 1993 whose spheres of operation overlap significantly, particularly in relation to plant genetic resources and intellectual property rights. Bowman states that this is because biological diversity, at both genetic and physical levels, is being exploited as the key ingredient for lucrative biotech and pharmaceutical industrial creation. Patent protection of that creation raises questions about biodiversity sustainability and also access to the resultant benefits and technologies derived from use of a raw product ‘owned’ by source countries or communities.

Currently we are experiencing global biodiversity degradation and decimation due to causes such as global warming that may result in the extinction of nearly half the current lifeforms by 2050. Bowman comments: ‘Apart from the intrinsic value of biological diversity, without healthy and diverse ecological systems on this planet there is no quality of life for humans — no fresh air or water, no arable land or edible food, and exposure to devastating storms, floods and droughts. But at the same time, humans are evolutionary creatures and we see that clearly with technological innovation. We are also wed to the dollar and we see that, in the context of this discussion, in the jealous guarding of rent for patents, specifically in the growing sector of biotechnology and pharmaceuticals based on plant genetic resources. So the question is how do we marry these components in a way that honours each of them? I look at this question from a purely legal standpoint. Undoubtedly any solution is complex, multi-faceted and multi-disciplined. Nonetheless, the legal principles embedded in the key international treaties on protection of biodiversity and protection of intellectual property rights in plant genetic resources share a commitment to global welfare enhancement. So it becomes clear that the legal foundations exist for cooperation between these two sectors. This knowledge paves the way for productive dialogue and action in boardrooms, patent offices and parliaments around the world.’

Related article from the Sciencebase archives on corporate academia: Will publicly funded research become mired in patent protection and intellectual property rights or remain purely altruistic?

(Updated: August 21, 2007)

Mice and a slice

Raman brain sliceA new methodology for fibre-optic Raman mapping and FTIR imaging of secondary cancer cells, metastases, and detecting tumour cells has been developed by researchers in Germany. The technique facilitates imaging of samples thicker than 50 micrometres and could be used in detecting cancer cells, as a tool for molecular histopathology, in metabolic fingerprinting, general disease diagnostics.

Team member Christoph Krafft is currently in the Department of Materials and Natural Resources, at the University of Trieste, Italy, but will be returning to Dresden University of Technology with a new research grant in September. I spoke to him about the research and he told me that, “This fibre-optic Raman method will allow detecting tumour cells and tumour tissue in vivo and enable studies of tumor development.” You can read more details in the latest issue of SpectroscopyNOW.com in the Raman ezine.