Boris Johnson, Fop or Geneticist?

boris johnsonFor Scousers, Londoners, fans of BBC’s Have I Got News for You satirical news quiz, and especially to everyone who watched this Beijing to London Olympic handover this week the name Boris Johnson likely drums up an image of some blonde, floppy haired, bedraggled and totally confused Tory toff, who just happens to be Mayor of London.

Well, it turns out that he has quite an interesting ancestry of which he was almost totally unaware until another BBC TV show (Who Do You Think You Are?, which is all about family history and genealogy of the rich and famous) helped him dig deep into the roots of his family tree. First off, not only was his great grandfather, Ali Kemal an outspoken journalist turned politician (like Johnson) who was apparently lynched by the state in the founding years of modern Turkey but his great-great-great-great-great-great-great-great grandfather was King George II of England (illegitimately due to a “wrong-side-of-the-sheets liaison between Johnson’s great grandmother and a descendant of George II. Such ancestry means Johnson is related to all the royal families of Europe.

How’s that for a bit of name dropping? Of course, there are probably tens of thousands of people who have illegitimate links to European royals, but it’s an interesting find nevertheless.

However, for those who think Johnson is nothing more than a blithering fop, it was his final words in this episode of “Who Do You Think You Are?” that were most poignant to lineage, heredity and most of all genetics, which is why I thought they warranted a holiday mention. I just hope they were spontaneous and unscripted.

We’re all just great, our genes just pulse down the lines. We’re not the ultimate expression of our genes. We’re the temporary custodians of these things. We don’t really know where they’ve come from, where they’re going, and the whole process is incredibly democratic.

You can view a segment from the show here, unfortunately, the closing quote is not included in this Youtube segment.

UPDATE: Following on from Mr Johnson’s genetic insights, I see there’s a paper in this week’s Nature from Cornell researchers that says: “One day soon, you may be able to pinpoint the geographic origins of your ancestors based on analysis of your DNA. The researchers describe the use of DNA to predict the geographic origins of individuals from a sample of Europeans, often within a few hundred kilometres of where they were born.”

Novembre, J et al (2008). Genes mirror geography within Europe Nature

Lighting Up Genetic Disease

Image analysisGenetic disease is a complicated affair. Scientists have spent years trying to find genetic markers for diseases as diverse as asthma, arthritis and cardiovascular disease. The trouble with such complex diseases is that they are none of them simply a manifestation of a genetic issue. They involve multiple genes, various other factors within the body and, of course, environmental factors outside the body.

There are some genetic diseases, however, that are apparently caused by nothing more than a single mutation in the human genome. A single DNA base out of the many thousands on a person’s genetic material, if swapped for another the wrong base means the production of the protein associated with that gene goes awry.

For example, sickle cell disease is caused by a point mutation in the gene for beta-haemoglobin. The mutation causes the amino acid valine to be used in place of glutamic acid at one position in the haemoglobin. This faulty protein cannot fold into its perfect active form, which in turn leads to a cascade of effects, that result ultimately in faulty red blood cells and their associated health problems for sufferers. There are many other diseases associated with single point mutations, including achondroplasia, characterised by dwarfism, in one sense, cystic fibrosis, although different single mutations may be involved, and hereditary hemochromatosis, an iron overload disease.

“To be able to study and diagnose such diseases with limited material from patients, there is a need for methods to detect point mutations in situ,” explains Carolina Wählby of the Department of Genetics and Pat Centre for Image Analysis, at Uppsala University, Sweden, and her colleagues Patrick Karlsson, Sara Henriksson, Chatarina Larsson, Mats Nilsson, and Ewert Bengtsson. Writing in the inaugural issue of the International Journal of Signal and Imaging Systems Engineering (2008, 1, 11-17), they pointed out that this is a problem that can be couched in terms of “finding cells, finding molecules, and finding patterns”.

The researchers explain that the molecular labelling techniques used by biologists in research into genetic diseases often just produce bright spots of light on an image of the sample. Usually, these bright spots, or signals, are formed by selective reactions that tag specific molecules of interest with fluorescent markers. Fluorescence microscopy is then used to take a closer look.

However, signals representing different types of molecules may be randomly distributed in the cells of a sample or may show systematic patterns. Such patterns may hint at specific, non-random localisations and functions of those molecules within the cell. The team suggests that the key to interpreting any patterns of bright spots relies on slicing up the image quickly, applying signal detection, and finally, analysing for patterns. This is not a trivial matter.

One solution to this non-trivial problem could lie in employing data mining tools, but rather than extracting useful information from large databases, those tools would be used to extract information from digital images of cells captured using fluorescence microscopy. The spatial distribution patterns so retrieved would allow labelled molecular targets to analysed that builds on the latest probing and staining techniques.

Biological processes could thus be studied at the level of single molecules, and with sufficient precision to distinguish even closely similar variants of molecules, the researchers say, revealing the intercellular and sub-cellular context of molecules that would otherwise go undetected among myriad other chemicals.

The team has demonstrated proof of principle by developing an image-based data mining system that can look for variants in the genetic information found in mitochondria (i.e. mitochondrial DNA, mtDNA). They point out that MtDNA is present in multiple copies in the mitochondria of the cell, is inherited together with cytoplasm during cell replication and provides an excellent system for testing the detection of point mutations. They add that the same approach might also be used to detect infectious organisms or to study tumours.

Wahlby, C., Karlsson, P., Henriksson, S., Larsson, C., Nilsson, M., Bengtsson, E. (2008). Finding cells, finding molecules, finding patterns. International Journal of Signal and Imaging Systems Engineering, 1(1), 11. DOI: 10.1504/IJSISE.2008.017768

Genetic Manipulation

European corn borer

Are you happy to eat genetically modified foods? What about your friends and colleagues? Do the GM pros outweigh the cons?

I asked a few contacts for some answers by way of building up to a more formal response to those kinds of questions that will be published soon in the International Journal of Biotechnology (IJBT, 2008, 10, 240-259).

Plant geneticist Dennis Lee, Director of Research at mAbGen, in Houston, Texas, suggests that GM crops have several significant advantages. “Total cost per acre can actually be significantly less for GM crops,” he says. This is particularly true for crop species, such as maize, that have been modified to produce natural toxins that fend off insect pests or protect the crop from the herbicides need to keep weed growth at a minimum. However, he points out that, “In practice, this is often not the case – farmers tend to err on the side of caution and continue to use significant amounts of pesticides and herbicides.”

That said, crops can also be modified to grow in substandard conditions, such as strains of tubers grown in Kenya that are capable of surviving both drought conditions and high-salt soils. “Obviously, this is beneficial to yield – you can actually get some food out of places where you previously could not,” adds Lee. In addition, it could be possible to modify some crops to have greater nutritional content, such as the so-called “golden rice” project by Ingo Potrykus then at the Institute of Plant Sciences of the ETH Zurich.

One of the biggest perceived problems regarding GM crops is the possible contamination of other species. What if herbicide-resistant genes could jump into weed species, for instance? Lee points out that this putative problem can be overcome by using terminator technology to jumping genes. “However, in doing so, it creates a different problem,” Lee adds, namely that farmers must buy seed from the agbiotech company each year rather than save seed for planting.” One might say that this is an exploitative industry focused purely on maximizing profits, but at the same time it solves a serious technical problem that has been seen as one of the biggest stumbling blocks to the acceptance of GM crops.

Jeff Chatterton, a Risk and Crisis Communications Consultant at Checkmate Public Affairs, in Ottawa, points out that the pros are well documented: increased yield per acre, ease of use and perhaps, some day, increased ‘consumer level’ benefits such as higher nutritional values. But, echoes others’ comments on the hidden con of farmers the world over potentially being locked into the agbiotech company’s seed and having no recourse to produce their own from one year to the next.

“As traditional family farms are increasingly moving towards “Roundup Ready” corn or soybeans, you’re increasingly seeing a change in the business model of farming,” he says. “Rather than ‘family farms’ using traditional farming practices, agricultural operations are increasingly becoming factory farms.” It might be said that the emergence of factory farms is occurring outside the realm of GM crops, but with pressure being applied to produce more and more crops for non-food purposes, including, biofuels, unique polymers, and other products, the notion of a factory farm that doesn’t even feed us could become an increasing reality.

Lee also mentions an intriguing irony regarding the public perception of risk-benefits concerning GM crops and that is that the toxins produced by modified Bt maize is exactly the same toxin produced by the natural soil microbe Bacillus thuringiensis (Bt) itself and this is same Bt toxin that so-called “organic” farmers are usually allowed to use instead of “synthetic” pesticides.

Information Technology and Services Professional Bill Nigh of Bluenog, based in New York, provides perspective as a lay person. “We’ve been engaged in genetic manipulation for a long time now,” he says, “but it was limited by the technology at hand. With recombinant DNA it’s a remarkably more vast field of play and a whole new ball game.” He stresses that his main concern regarding GM crops is that, “We seem to be just smart enough to make drastic breakthroughs and inventions, and are driven by the dynamics of the marketplace and ego to produce a lot of new things quickly. However our systems of governance, oversight and coordination are not mature enough to work through the implications of those new things in a timely fashion, especially the unforeseen synergies the breakthroughs can unleash.”

All that said, an international team has now investigated the various issues and has assessed the public’s Willingness to Accept (WTA) GM foods based on experimental auctions carried out in France, UK, and USA. Lead author of the IJBT paper Wallace Yee now at the University of Liverpool, worked, while at Reading University, with colleagues in various disciplines, from agricultural and food to business and economics in Italy, New Zealand, UK and US to explore perceptions of risk and benefits, moral concerns and attitudes to the environment and technology.

“Trust in information provided by industry proved to be the most important determinant of risk/benefit perceptions,” the researchers conclude, “willingness to accept followed general attitudes to the environment and technology.” They also found that educational level and age could also enhance perceived benefits and lower perceived risks of GM foods. “Our research suggests that trust-building by industry would be the most effective approach to enhancing the acceptance of GM foods,” the team says.

“If the industry could educate people that GM technology does not pose any threat to the environment, but provides benefits to society as a whole and consumers as individuals, the attitudes of the public towards GM in food production would be favourable, and in turn increase their willingness to accept,” they conclude.

Computing professional Paul Boddie of Oslo, Norway, coming at the issue of GM crops from an indirect angle provides an allusion to computer programming that seems quite pertinent and was originally attributed to Brian Kernighan, which Boddie suggests readily transfers to other disciplines including genetic engineering: “Everyone knows that debugging is twice as hard as writing a program in the first place. So if you are as clever as you can be when you write it, how will you ever debug it?”

Yee, W.M., Traill, W.B., Lusk, J.L., Jaeger, S.R., House, L.O., Moore, M., Morrow, J.’., Valli, C. (2008). Determinants of consumers’ willingness to accept GM foods. International Journal of Biotechnology, 10(2/3), 240. DOI: 10.1504/IJBT.2008.018356

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.

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.

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.

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)

Ragworm Ragtime

RagwormWhen I was a youngster I used to do a spot of sea fishing on the freezing cold north east coast. It wasn’t so much a hobby as an obsession at one point. Key to success was a plentiful supply of lugworm which could be dug from the wet golden sand at lowtide and stored ready for the next angling venture, while ragworm, which have a nasty bite, came from the local fishing bait supplier. Never would it have occurred to my 11-year old self that these lowly creatures could harbour the secrets of our own evolution.

However, apparently it does. Detlev Arendt of the European Molecular Biology Laboratory has been studying the multifunctional neurones that sense the environment and release hormones in vertebrates (including ourselves), flies, and worms. The last common ancestor of all of these creatures must provide the evolutionary basis of our modern brains that endow us with the skills to varying degrees of success to dig up ragworm, take part in fishing trips, and ponder our origins.

Hormones control growth, metabolism, reproduction and other biological processes. In humans, as indeed in all vertebrates, the chemical signals are produced by the hypothalamus and other specialist brain centres and secreted into the blood for circulation around the body. This signalling system is not, it turns out, the preserve of those creatures with a backbone. Arendt and his colleagues now believe that the hypothalamus and its hormones have their evolutionary origins in an ancient worm-like creature that lived hundreds of millions of years ago and is the common ancestor of vertebrates, flies, and worms.

Hormones work slowly, on the whole, and have body-wide effects. Insects and nematode worms use hormones, but the specific molecules they use are very different from their vertebrate counterparts.

“This suggested that hormone-secreting brain centres arose after the evolution of vertebrates and invertebrates had split,” explains Arendt, “But then found vertebrate—type hormones in annelid worms and molluscs, indicating that these centres might be much older than expected.” Comparisons of two types of hormone-secreting nerve cells from zebrafish, a vertebrate, and the annelid worm Platynereis dumerilii, in Arendt’s lab have now revealed some stunning similarities that point to a shared and ancient ancestry for our hormonal systems.

“These findings revolutionise the way we see the brain,” says Kristin Tessmar-Raible who carried out the comparison, “So far we have always understood it as a processing unit, a bit like a computer that integrates and interprets incoming sensory information. Now we know that the brain is itself a sensory organ and has been so since very ancient times.” The research appears in detail in the journal Cell.

Bewildering to think that I used to skewer these little creatures on a barbed hook and cast them into the sea to catch scaly marine creatures. It almost makes no sense.

DNA Network

DNA Network logoSciencebase was recently invited to join the excellent DNA Network and as such our genetics news feed is now being pulled by the network’s feed system. If I had been a little slower off the mark, I could have been site number twenty in the list, but when I joined I think I jumped in at #18. There are, at the time of writing, nineteen members, no DNAying it.

So, here is a quick random selection of fellow network members. The links will take you to the individual RSS feed for each site whereby you can subscribe (for free) and get some great and timely information on DNA and the latest happenings and business news in genetics and DNA research.

VentureBeat Life Sciences

Discovering Biology in a Digital World

DNA Direct Talk

Epidemix

The Daily Transcript

henry: the human evolution news relay (genetics)

Mary Meets Dolly

Genetics News

Microarray and Bioinformatics

Gene Sherpas: Personalized Medicine and You

The Personal Genome

All excellent newsfeeds, all focused on one thing, DNA. You can find links to the others, including Eye on DNA, the owner of which led me to the DNA Network in the first place, via DNA Network. I’ll do another round-up of the remaining members later.

Genetic Research Hits Pay Dirt

DNAThe budget for the Human Genome Project and all that post-genomic, proteomic, metabonomic, immunomic…research was almost on a par with defense spending; it was almost c-omical really. Well, maybe not quite, but it stretches out with a lot of zeros nevertheless. At the time the grants were written and the funding given, we, as a society, were promised all kinds of medical miracles from gene therapies and new treatments to cure all those nasties – cystic fibrosis, sickle cell, thalassemia, cancer, heart disease and more.

We were promised personal medicine courtesy of pharmacogenomics. This would allow your doctor to profile your genome and tailor your medication to the particular set of enzymes running in your liver and whether or not you were likely to respond positively, suffer adverse effects, or simply not respond at all. We have even seen, this last few days, the sequencing of James Watson’s genome; an effort that cost less than $1m and took under four months. But do any of these promises add up to very much beyond myriad PhD theses and thousands of biotech startups many of which have already crashed?

Hopefully, the answer is yes. In the next few years, gene science will hit pay dirt as genes finally give up their real secrets and the true meaning of so-called junk DNA will become clear. Our understanding and ability to treat a wide range of disease from breast cancer and obesity to hypertension and bipolar disorder will come of age and perhaps finally succumb to all this genetic scrutiny and manipulation.

Nature, Science and the Wellcome Trust provided a useful summary of the genetic state of the art for a recent Times report by Mark Henderson on our genetic future. In the summary Henderson highlighted the latest “in press” results, most of which are now online, so I am providing here the hyperlinked executive summary:

Breast cancer – Three papers published in Nature and Nature Genetics at the end of May reported four new genes and one genomic region associated with increased risk. 10.1038/nature05887, 10.1038/ng2075, 10.1038/ng2064

Obesity – An obesity gene, the FTO gene, was published in Science in April and reported in Sciencebase at the time.

Diabetes – Again in Science (and 10.1126/science.1142382 and 10.1126/science.1142358, three common genes for increased diabetes type 2 risk were reported, bringing the total known genes associated with diabetes to nine.

Alzheimer’s disease – New results also published this week in Neuron discuss an Alzheimer’s gene

Data that were still under press embargo at the time Henderson’s feature appeared in The Times, however, meaning he could only hint at the true potential of human genome results were revealed today.

The largest ever study of genetics of common diseases in which almost 10 billion pieces of genetic information were analysed were published just one minute ago, so I can now outline the findings in a little detail. The new study compared 2000 cases each of seven common diseases with 3000 shared control patients, and reveals new genetic associations with these disorders. A pair of related papers in Nature Genetics (a and b) offer further insights into two of the seven diseases investigated.

In the Nature article, scientists from the Wellcome Trust Case Control Consortium report genetic variants associated with the development of bipolar disorder, Crohn’s disease, coronary heart disease, type 1 and type 2 diabetes, rheumatoid arthritis and hypertension. This is the first study from this large scope and it, the scientists found one genetic region newly associated with bipolar disorder, and another with coronary artery disease. A separate group of three markers have been found to be associated with rheumatoid arthritis. The researchers also identify nine new genetic associations for Crohn’s disease and ten chromosome regions that contain genes related to diabetes.

These new results would suggest a medical revolution is at hand and that the Human Genome Project and its spinoff -omics really are about to hit pay dirt. But, are we really on the verge of a new era in medicine, or are the various genetic revelations simply more grant-baiting hyperbole?