KQED Public Broadcasting in San Francisco recently did a radio story about the UC San Francisco Canine Behavioral Genetics Project run in collaboration with the University of Pennsylvania. The aims of the project are:

1. To explore the relationship between genes and behavior, both normal and abnormal, in domestic dogs.

2. To assess the amount and nature of genetic diversity in domestic dogs, both within and between breeds. 

Melanie Chang of the CBG project

Anyone wishing to send in their dog’s DNA can visit the site:

http://www.k9behavioralgenetics.com/ 

Dog DNA samples waiting to be processed at the CBG project 

However, it is often said dogs and their owners resemble each other. Now, researchers within this project are looking for those connections on a whole new level. They’re searching for the genes that cause common psychiatric problems in humans - by looking at the DNA of dogs. Have a listen to this very interesting broadcast:

http://www.kqed.org/quest/radio/view/836

Elaine Warburton  www.geneticsandhealth.com

In January, The New England Journal of Medicine published an article criticizing the popularization of genetic testing by companies such as 23andme, deCode, Navigenics and Knome who doctors believe are introducing genetic testing prematurely into a commercial setting and confusing public and medics alike.  The authors of this article coined the phrase ‘recreational genomics’ for this type of testing.

While all of these companies claim that their tests should not be used as the basis for medical decisions, some physicians are concerned that customers for these tests will nevertheless begin seeking medical direction based on their results.  Doctors have been unprepared for the genetic advice they need to give their patients. 

The British Medical Journal has also published an equally critical article on the commercialization of genetic testing written by Exeter University Professor of Epidemiology and Public Health, David Melzer, whose own interest lies in research on genetic and conventional risk factors for chronic conditions of ageing.

Among the author’s concerns, is the need for strong regulatory oversight of genetic tests, tests based on empirical evidence, and public and physician education based on sound and transparent information.

“Although major scientific progress has been made, clinical applications are still mostly unclear,” Melzer wrote.

He suggests the key value of genetic markers may be in providing clues about disease mechanisms. On the other hand, he argues that few of the current markers are useful diagnostically, particularly those associated with moderately increased risk and/or with conditions for which no preventative interventions are available.

My personal belief is that introducing innovative genetic testing technology has to start somewhere.  With genetics we will never understand 100% of the complexities and interactions between our DNA and the environment - that is for the ‘divine being’ to know.  These genomic companies have taken a huge financial and clinical risk in bringing these tests to the market.  The tests are in their infancy and each of these companies are transparent in advising their customers of this fact.  That said, massive scientific research continues to take place to build on the knowledge base of these tests, so that they may be refined.  This process will never end.

Most people are fascinated by their own health and mortality.  Millions are spent on a plethora of mainly unproven herbal drugs and vitamins that have the potential to damage an individual. Many more millions are spent on early stage gadget technology.  If an individual wishes to understand more about their genetic risk of developing a disease and testing is available then it is also their right to purchase a test.  Surely commonsense dictates that raising an individual’s awareness of their risk of developing a disease is a good thing, particularly if that individual takes control of their health and well-being by perhaps eating more sensibly and taking more exercise?

In terms of patient education and support, these genomic companies are providing some pretty in-depth advice which customers have access to.  In terms of doctors providing more information and education on genetic testing, the question needs to be asked as to why medical schools are not preparing doctors sufficiently in this area? Genetics and the knowledge of the role it will play in diagnostics has been around for a good 30 years! Genetics and genetic testing should be part of the core medical training syllabus and ongoing professional education. 

… and for that matter it also needs to be taught as part of the school syllabus.  Genetics has come along way since Gregor Mendel’s pea plant experiments in the 1850’s and yet that is still the level of subject knowledge our kids are being taught!

Elaine Warburton  www.geneticsandhealth.com

‘Clover structure’ of Transfer RNA 

Transfer RNA (tRNA) is ancient. It is the most direct intermediary between genes and proteins. Like many other RNAs (ribonucleic acids), tRNA aids in translating genes into the chains of amino acids that make up proteins. The fact that tRNA is so central to the task of building proteins probably means that it has been around for a long time.

Professor Gustavo Caetano-Anollés and Feng-Jie Sung of Univeristy of Illinois-Urbana Champaigne had a hunch that understanding the structural properties of tRNA would shed light on how organisms and viruses evolved.

All tRNAs assemble themselves into a shape that, if flattened, resembles a cloverleaf. The team began by looking for patterns in this cloverleaf structure, using detailed data from hundreds of molecules representing virusesand each of the three superkingdoms of life: archaea (microbes that can survive in boiling acid, near sulfurous ocean vents or in other extreme environments), bacteria and eukarya.

“Perhaps in evolution there are things that are so fundamental that they are kept, held onto, for millions or even billions of years,”Caetano-Anollés said. “Those are the fossils, the molecular fossils, that tell us about the past. Therefore, studying these molecules can address fundamental questions in biology and evolution”.

They conducted the same analysis on the tRNAs of each of the superkingdoms, to see how far these groupings diverged from the overall tree. This comparison allowed them to determine the order in which viruses and each of the superkingdoms diverged.

The new analysis supports an earlier study that suggested that the archaea were the first to arise as an evolutionarily distinguishable group. The research also indicated that viruses emerged not long after the archaea, with the superkingdoms eukarya and bacteria following much later - and in that order.

This finding may influence the ongoing debate over whether viruses existed prior to, or after, the emergence of living cells, Caetano-Anollés said.

Elaine Warburton  www.geneticsandhealth.com

(Image courtesy of www.ustc.edu.cn) 

Latest news from the GenomeWeb:

“The Beijing Genomics Institute at Shenzhen announced that it is launching an International Giant Panda Genome Project.

Scientists at BGI-Shenzhen plan to sequence a panda to be selected from the Chengdu and Wolong breeding centers using high-throughput sequencing technology. They hope to have a draft genome sequence assembled within six months. The giant panda genome is roughly the same size as the human genome and contains some 20,000 to 30,000 genes.

The project is intended to provide new insights into panda ecology and evolution. This could shed light on the panda’s history, migration, and relationships to other animals, as well as information about panda fitness and diseases that may help protect the endangered animals. Eventually, the team plans to do panda transcriptome studies and studies on genetic variations in the panda population.

“It is the first genome project to be undertaken specifically to gather information that will contribute to conservation efforts for an endangered species,”Oliver Ryder, an endangered species researcher at the San Diego Zoo who participated in a Panda Genome workshop held in Shenzhen earlier this year, said in a statement. “The giant panda is a global conservation symbol and deserving of such an effort.” “

Elaine Warburton  www.geneticsandhealth.com

Galileo’s tomb 

Over 360 years ago Galileo died living as a recluse in Italy, a convicted heretic.  His crime - he fell foul of the religious authorities of the day by arguing that the Earth revolved around the sun and not vice versa.  His theory was subsequently found to be perfectly true.

Italian researchers, led by Prof Paulo Galluzzi, want to exhume his body from the city’s Basilica of the Holy Cross, for DNA tests to find the cause of the blindness that afflicted him. They also want to confirm, through DNA profiling, whether the body that shares his grave is that of Galileo’s beloved daughter, Sister Marie Celeste.

The rector of the basilica is having none of it - describing the plan as disrespectful.  The debate continues.

Elaine Warburton  www.geneticsandhealth.com

(The Smiling Faces of Boddhastavas, Cambodia)

Ever the eternal optimist, here’s a piece of research which I can really relate to … Psychologists at the University of Edinburgh working with researchers at Queensland Institute for Medical Research in Australia found that happiness is partly determined by personality traits and that both personality and happiness are largely hereditary.

Rating personalities with the ‘Five factor model’ the researchers found that people who do not excessively worry, and who are sociable and conscientious tend to be happier. The findings suggest that those lucky enough to have the right inherited personality mix have an ‘affective reserve’ of happiness which can be called upon in stressful times or in times of recovery.

Dr Alexander Weiss, of the University of Edinburgh’s School of Philosophy, Psychology and Language Sciences, who led the research said: “Together with life and liberty, the pursuit of happiness is a core human desire. Although happiness is subject to a wide range of external influences we have found that there is a heritable component of happiness which can be entirely explained by genetic architecture of personality.”

Elaine Warburton www.geneticsandhealth.com

Further to my various articles on our ancestry, differences in gene expression levels between people of European versus African ancestry appear to affect how each group responds to certain drugs or fights off specific infections, report researchers from the University of Chicago Medical Center and the Expression Research Laboratory at Affymetrix Inc. of Santa Clara, CA.

The researchers used lymphoblastoid cell lines derived from blood from 180 healthy individuals. They studied 60 nuclear families, including mother, father and child. Thirty of the families were Caucasians from Utah and 30 were Yorubans from Ibadan, Nigeria.

Mainly focusing on cancer treatments, the researcher sought to understand why different populations experienced different degrees of toxicity when taking certain drugs and also to learn how to predict who might be most at risk for drug side effects.

But in the process they saw several other differences. Some, including variation in the immune system’s response to microbial invaders, were expected. Previous studies have found that African Americans may be more susceptible than Caucasians to infection by certain bacteria, such as Porphyromonas gingivalis that causes periodontitis.

Others were unanticipated, including significant differences in expression levels among genes involved in fundamental cellular processes such as ribosomal biogenesis, transfer RNA processing, and Notch-signaling–part of a complex system of communication that governs basic cellular activities and coordinates cell actions.

For more information on this article, click on:

http://www.uchospitals.edu/news/2008/20080228-expression.html

Elaine Warburton  www.geneticsandhealth.com

Papers published in Nature and Science this week support the previously held theory that humans originated in East Africa, migrating outward until they reached all parts of the globe. But the genetic work from these studies brings a new level of precision to human migration studies, with each group finding subtle and intriguing details that shed light on different aspects of human genetic variation and ancestry.

Study 1 - University of Michigan:This study was based on the analysis of more than 500,000 SNPs and nearly 400 copy number variants — sections of DNA that are repeated or duplicated in the genome — for 485 individuals. These samples, representing individuals from 29 different populations around the world, were obtained as part of the Human Genome Diversity Project.

The results suggest East Africans are the most genetically diverse, while Native American genomes exhibit the lowest genetic diversity. Middle Eastern, Asian, and European populations, on the other hand, fall somewhere in between.  By following this decline in diversity, the Michigan team was able to retrace global human migration patterns. Consistent with previous archaeological date, language studies, and smaller genetic studies of mitochondrial DNA or autosomal or sex chromosomes, the research suggests humans originated in Africa, migrating first to the Middle East, then to Europe, Asia, the Pacific Islands, and — eventually — the Americas.

Study 2 - Cornell University: This study used comparative genomics to analyze 39,440 autosomal SNPs in 10,150 sequences from 15 African-Americans and 20 European-Americans.  Using the PolyPhen computer algorithm, they also assessed how many of the nucleic acid changes in each population were likely to produce amino acid changes that were “possibly” or “probably” damaging.

The researchers observed that the overall genetic diversity was higher in those of African descent, they found that those of European descent had more genetic variations that were predicted to be damaging. The authors attribute this to differences in population age and suggest European populations may have undergone a more recent population bottleneck — a decrease in population that leads to the selection of certain genetic traits — than their African ancestors.

Study 3 - Stanford Human Genome Center: This large study assessed 642,690 SNPs from 938 individuals from 51 populations and measured the genetic variation at each of the loci  and provided valuable information into human genetic variation both on a global scale as well as within relatively small geographic areas.

Specifically, the study found evidence for decreasing haplotype heterozygosity in populations as they moved further and further away from Addis Ababa, Ethiopia.  The study also found genetic evidence for differences in ancestry within populations. For instance, some individuals from the Middle East, such as Palestinians, Druze, and Bedouins, had ancestors from the Middle East as well as Europe and parts of South and Central Asia.

The results of these studies, while intriguing from a human ancestry perspective, may also provide insights into interpreting the genetics of some diseases, since they provide a framework for understanding genetic variation.

Elaine Warburton  www.geneticsandhealth.com
 

Our early human ancestors originated from a hot, humid climate where natural selection focused on dispersing heat.  As humans migrated to colder climates there would have been evolutionary pressure to adapt to their new settings by boosting the processes that produce and retain heat.

Genes involved in energy metabolism are therefore likely to be central to heat and cold tolerance. 

Researchers from the Dept of Human Genetics, University of Chicago, USA tested this theory by genotyping 873 tag SNPs in these ‘cold tolerance’ genes in 54 worldwide populations and found a correlation with climatic variations.

Among the results were strongest signals from several SNPs, that had previously been associated with body evolution directly related to cold tolerance.

One, a leptin receptor,  LEPR R109K, which is integral in appetite regulation and energy balance, was the source of one of the strongest signals of evolutionary selection. One version of this gene is common in locations with colder winters. This allele is additionally correlated with the increased capability to absorb oxygen and expel carbon dioxide, which happens when the body produces heat. The same genetic variation has also been linked to a lower BMI, a smaller amount of abdominal fat, and a lower blood pressure. This specific leptin receptor, therefore, is protective against metabolic syndrome.

However, not all of the genes related to tolerance of colder climates protects against the metabolic syndrome. For example, an increased blood glucose level might protect the body from cold weather by making energy more readily available for production of heat. However, this also raises the risk of type 2 diabetes. FABP2 A54T was a gene that was more prevalent in populations with lower temperatures actually increases BMA, promotes storage of fat in the body and increases levels of cholesterol. While this protects the body against the cold, it increases the risk of heart disease and diabetes, and thus metabolic syndrome.

Variation in climate may be correlated with other aspects of environmental variation. Nevertheless, the results are consistent with the idea that climate has been an important selective pressure acting on candidate genes for common metabolic disorders such as obesity, diabetes and heart disease.

Thousands of years later we live in an era that combines widespread central heating with an overabundant food supply, so those genetic alterations which protected us from cold have taken on a different sort of significance. They alter our susceptibility to a whole new set of diseases, such as obesity, coronary artery disease and type 2 diabetes.

For further information, please click on:

http://genetics.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pgen.0040032&ct=1

Elaine Warburton  www.geneticsandhealth.com