Fattened monkeys as a proxito human obesity

Fattened monkeys as a "proxi" to human obesity?

BEYOND. In today's edition of The New York Times (cover page) was published an article about using monkeys in different primate research centers to study obesity in humans. The main centers are the Oregon National Primate Research Center and the Southwest National Primate Research Center in San Antonio, Texas. Some studies are reporting results on how high fructose corn syrup appears to accelerate the development of obesity and diabetes. While these results sound promising, we should ask if this animal model (closer to us than rats) and the treatment applied (specific diet and intake) is a real "proxi" to human diet / lifestyle and human reaction to that particular experimental conditions. Monkeys (macaques and baboons) are pushed to changed their diets and lifestyles (wild vs. cage) in a short (really short) period of time; while humans are dealing with lifestyle and diet changes since the agriculture revolution (approximately 12,000 ya). In my graduate class (last Fall) about human evolution in health and disease (ANTH 650), and a recent seminar in a colleague's class (ANTH 612) we discussed human obesity taking into consideration the evolutionary perspective, where not only today's diet and lifestyle must be analyzed but past environments and habits must be included in the discussion.
I was happy when reading in the same article (NYT) a colleague's comment where he points out that he "prefers animals that become naturally obese with age, just as many humans do".

Types of Gene therapy and general strategies

Types of Gene therapy and general strategies

Gene therapy may be classified into two types

1) Germ line gene therapy

2) Somatic cell gene therapy

a) Incase of germ line gene therapy germ cells that is sperms or eggs are modified by the introduction of functional genes, which are ordinarily integrated into their genomes.


Therefore the change due to therapy is heritable and passed onto the later generations. This approach, heretically, is highly effective in counteracting the genetic disorders. However this option is not consider, at least for the present for application in human beings for a variety of technical and ethical reasons.

b) In the case of somatic cell gene therapy the gene is introduced only in somatic cells, especially of those tissues in which expression of the concerned gene is critical for health. Expression of the introduced gene relieves symptoms of the disorder, but this effect is not heritable, as it does not involve the germ line. It is the only feasible option, and clinical trials have already started mostly for the treatment of cancer and blood disorders.

GENERAL GENE THERAPY STRATEGIES

1) Gene augmentation therapy (GAT): -

It is done by simple addition of functional alleles has been used to treat several inherited disorders caused by genetic deficiency of a gene product. It is also involved in transfer to cells of genes encoding toxic compounds (suicide genes) or prodrugs (reagents which confer sensitivity to subsequent treatment with a drug). It has been particularly applied to autosomal recessive disorders where even modest expression levels of an introduced gene may make a substantial difference.

2) Targeted killing of specific cells: -

Artificial cell killing and immune system assisted cell killing have been popular in the treatment of cancers. It can be done by two ways.

a) Direct cell killing: - it is possible if the inserted genes are expressed to produce a lethal toxin (suicide genes), or a gene encoding a prodrug is inserted, conferring susceptibility to killing by a subsequently administered drug. Alternatively selectively lytic viruses can be used.

b) Indirect cell killing: - It uses immunostimulatory genes to provoke or enhance an immune response against the target cell.

3) Targeted mutation correction: -

The repair of a genetic defect to restore a functional allele, is the exception, technical difficulties have meant that it is not sufficiently reliable to warrant clinical trails.

4) Targeted inhibition of gene expression: -

It is suitable for treating infectious diseases and some cancers. If disease cells display a novel gene product or inappropriate expression of a gene a variety of different systems can be used specifically to block the expression of a single gene at the DNA, RNA or Protein levels.
REFERENCE

1) Tom strachan and Andrew P. Read, Human Molecular Genetics, Second edition.

2) T.A. Brown, Gene Cloning an introduction, Third Edition.

3) S.N. Jogdand, Gene Biotechnology.

4) B.D Singh, Biotechnology.

Human Gene Therapy

Human Gene Therapy
Human beings suffer from more than 5000 different diseases caused by single gene mutations, e.g., cystic fibrosis acatalasis, hunting tons chorea, tay sachs disease, lisch nyhan syndrome, sickle cell anemia, mitral stenosis, hunter's syndrome, haemophilia, several forms of muscular dystrophy etc. In addition, many common disorders like cancer, hypertension, atherosclerosis and mental illness seem to have genetic components.

The term gene therapy can be defined as introduction of a normal functional gene into cells, which contain the defective allele of concerned gene with the objective of correcting a genetic disorder or an acquired disorder.
The first approach in gene therapy is: -

a) Identification of the gene that plays the key role in the development of a genetic disorder.

b) Determination of the role of its product in health and disease.

c) Isolation and cloning of the gene.

d) Development of an approach for gene therapy.

The genetic material may be transferred directly into cells within a patient, which is referred as in vivo gene therapy or else cells may be removed from the patient and the genetic material inserted into them, which is referred as invitro gene therapy. Apart from the two methods mentioned above there is one more method that is ex-vivo gene therapy in which genetic material is inserted into the cells just prior to transplanting the modified cells back into the patient.

Major disease classes under gene therapy include: -

a) Infectious diseases: - infection by a virus or bacterial pathogen

b) Cancers: - uncontrolled and enormous cell division and cell proliferation as a result of activation of an oncogene or inactivation of a tumors suppressor gene or an apoptosis gene.

c) Inherited disorders: - genetic deficiency of an individual gene product or genetically determined in appropriate expression of a gene.

d) Immune system disorders: - includes allergies, inflammation and also autoimmune diseases in which immune system cells appropriately destroy body cells.

Telomerase: A Cancer Therapeutic Target

Telomerase: A Cancer Therapeutic Target


Although Elizabeth Blackburn had identified telomerase in 1980, it took 29 years for her work to be truly recognised. In 2009, Blackburn and her esteemed colleagues were awarded the Nobel Prize in Physiology or Medicine based on the successful ‘discovery of how chromosomes are protected by telomeres and the enzyme telomerase’ (Nobelprize.org, 2012).


As a result of this initial discovery, many scientific studies and research projects have aimed to further understand telomerase and the way in which it is related to degenerative diseases, aging and cancer (Reece, 2011). One such study was conducted by Jian Hu from the Dana-Farber Cancer Institute, Boston, USA. Titled ‘Antitelomerase Therapy Provokes ALT and Mitochondrial Adaptive Mechanisms in Cancer’, the study looked at modeling telomerase reactivation through the use of an inducible telomerase reverse transcriptase allele (Hu, 2012).

The starting point for a mutation has been found to be related to a problem which can arise during cell division if the subject (mouse) has levels of the enzyme which are low or nonexistent. When this factor is married with conventional DNA polymerases exhibiting an end-replication problem a normal or premalignant cell can lose the essential telomere sequences and uncapping can occur (Hu, 2012). This leads to the activation of cellular checkpoints not unlike those caused by DNA double-stranded breaks and ultimately results in telomere dysfunction (Hu, 2012). Flow on effects of dysfunction can be seen with records of induced p53 (tumor suppressor protein), cellular senescence and apoptosis (Children’s Medical Research Institute, 2006). Mutational inactivation of the p53 protein allows for cell cycling to continue and provides a procarcinogenic mutator mechanism for cells with telomere dysfunction via translocations, amplification and deletions (Hu, 2012). However, continual dysfunction and uncontrolled chromosomal instability can restrict full malignant progression.

As a result, clinically derived inhibitors with oligonucleotide changes enable maintenance of telomeres through homologous recombination. The alternative lengthening of telomeres (ALT) mechanism is one such inhibitor. By engineering an allele, TERT (a reverse transcriptase catalytic subunit) which can be inserted into the genome, and using mice mutant for Atm, the development of high penetrance and T cell lymphomas was able to be modeled. Results showed that mice from either the parental or first generation with the allele 4-Hydroxytamoxifen (4-OHT)-inducible Telomerase Reverse Transcriptase-Estrogen Receptor (TERTER) developed T cell lymphomas at synonymous penetrance and latencies. In comparison, the third and fourth generation mice presented lymphomas with lower penetrance and longer latency (Hu, 2012), refer to Figure 2.

Several key genes including those that were regulated from a master regulator possessed deviant expression in relation to oxidative and mitochondria pathways. The PGC-1ß, believed to control mitochondrial oxidative energy metabolism by activating specific target transcription factors including estrogen-related receptors (Sonoda, 2007), was found to be a major driver of the adaptive response to telomere dysfunction (Hu, 2012), refer to Figure 3.


The pressure for a cell to maintain mitochondrial function is directly relatable to the ROS (reactive oxygen species) levels and may be of great importance to telomeres due to ROS destroying telomeric G-rich sequences. Thus confirming the PGC link (refer to Figure 4) between mitochondria, telomeres and carcinogenic cells (Hu, 2012).


Furthermore, rendering genetic modelling crucial in the desire to understand tumor cell response, and quite possibly providing the answer to curing cancer.

Genetic Testing

Genetic Testing

This last century has seen an escalation in advancement of technology. In about one hundred years, man has gone from the horse and buggy to super sonic flight. These advancements have also been implanted in the health industry as seen in the almost doubling of the life expectancy of man.It also appears as though this escalation will only continue. One field where these advancements are moving at a very high speed is the field of genetics and biotechnology. The last ten years have seen some of the greatest landmarks in genetic genealogy research. The pattern in this field indicates that the discoveries and applications of those discoveries will continue to grow at an exponential rate.

With the increase in genetic knowledge there has also been an increase in the variety and ease of genetic testing available. Genetic testing refers to any sort of test which involves the study of the genome. When genetics was in its infancy, tests were expensive and took a long period of time to perform. Recent advances have significantly decreased the costs and time needed to perform genetic testing. This decrease in cost and time has made genetic testing available to more of the general public.

Genetic testing has also been used for determining family relationships. The simplest relationship to determine with a genetic test is a paternal or a maternal relationship. Today, genetic testing can also be used to determine other, more distant relationships. Genetic testing is available for full siblings, half siblings, grandparents and cousins. This allows family relationships to be determined even if one or more of the family members is deceased. As research continues, the ability to dive deeper into your family tree is becoming possible. With the use of Y-chromosome and mtDNA (mitochondrial DNA) testing more can be learned. The use of these genetic tests has allowed genealogists to verify their family trees and in some cases discover new branches that were not previously known. Genetic testing is even being used to understand the roots of family trees. This includes the use of genetic tests to look for Native American ancestry, and ancestry from different parts of Europe and Asia.

As knowledge and research in the area of genetics and biotechnology continue to advance, genetic testing will become even more accessible. This increase in use of genetic tests will give people more access to information. This information can be used to help solve crimes, increase the quality of health care, and provide information into your personal or family history.

Gene Therapy - Viral Vectors

Gene Therapy - Viral Vectors

In both types of therapy, scientists need something to transport either the entire gene or a recombinant DNA to the cell's nucleus, where the chromosomes and DNA reside. In essence, vectors are molecular delivery trucks. One of the first and most popular vectors developed were viruses because they invade cells as part of the natural infection process. Viruses have the potential to be excellent vectors because they have a specific relationship with the host in that they colonize certain cell types and tissues in specific organs. As a result, vectors are chosen according to their attraction to certain cells and areas of the body.

One of the first vectors used was retroviruses. Because these viruses are easily cloned (artificially reproduced) in the laboratory, scientists have studied them extensively and learned a great deal about their biological action. They also have learned how to remove the genetic information that governs viral replication, thus reducing the chances of infection.

Retroviruses work best in actively dividing cells, but cells in the body are relatively stable and do not divide often. As a result, these cells are used primarily for ex vivo (outside the body) manipulation. First, the cells are removed from the patient's body, and the virus, or vector, carrying the gene is inserted into them. Next, the cells are placed into a nutrient culture where they grow and replicate. Once enough cells are gathered, they are returned to the body, usually by injection into the blood stream. Theoretically, as long as these cells survive, they will provide the desired therapy.

Another class of viruses, called the adenoviruses, also may prove to be good gene vectors. These viruses can effectively infect nondividing cells in the body, where the desired gene product then is expressed naturally. In addition to being a more efficient approach to gene transportation, these viruses, which cause respiratory infections, are more easily purified and made stable than retroviruses, resulting in less chance of an unwanted viral infection. However, these viruses live for several days in the body, and some concern surrounds the possibility of infecting others with the viruses through sneezing or coughing. Other viral vectors include influenza viruses, Sindbis virus, and a herpes virus that infects nerve cells.

Scientists also have delved into nonviral vectors. These vectors rely on the natural biological process in which cells uptake (or gather) macromolecules. One approach is to use liposomes, globules of fat produced by the body and taken up by cells. Scientists also are investigating the introduction of raw recombinant DNA by injecting it into the bloodstream or placing it on microscopic beads of gold shot into the skin with a "gene-gun." Another possible vector under development is based on dendrimer molecules. A class of polymers (naturally occurring or artificial substances that have a high molecular weight and formed by smaller molecules of the same or similar substances), is "constructed" in the laboratory by combining these smaller molecules. They have been used in manufacturing Styrofoam, polyethylene cartons, and Plexiglass. In the laboratory, dendrimers have shown the ability to transport genetic material into human cells. They also can be designed to form an affinity for particular cell membranes by attaching to certain sugars and protein groups.

Early migration of modern humans into Arabia.....but from where?

Early migration of modern humans into Arabia.....but from where?

TOOLS. Stone tools (hand axes) were unearthed in the Arabian peninsula in a rock shelter called Jebel Faya. These tools were dated as old as 127,000 years as it was presented in Science last January. The authors suggest that this early expansion of anatomically modern humans took place from Africa and then added that "It is likely that populations expanded and moved through the interior of Arabia, as well as via the coastline, and used adaptive strategies incorporating terrestrial resources" But, other researchers do not share this idea. John Shea of Stony Brook University in New York pointed out that "stone points from Jebel Faya are shorter, thicker and less pointy than those found throughout Africa beginning 100,000 years ago" Moreover, he proposes that the stone tools similarities of Jebel Faya to Indian finds could reflect a different migration, one that came from Asia. Now the debate is open and waiting for more evidence.

Creative Explosion: European caves or South African Caves?

Creative Explosion: European caves or South African Caves?

TOOLS and BEYOND. Back again and trying to catch up with some news. An article published in the August issue of Scientific American magazine presents a general review from the work conducted in the last two decades by archaeologist Curtis Marean and his team on coastal South African sites. His main findings challenge the previous hypothesis that suggests that earliest modern human behaviors were all found in Europe around 40,000 years ago (and suggesting that this was the departure "place"). The authors wrote that at Pinnacle Point they found evidence that supports the idea that modern humans (at Pinnacle Point) "may be very well the ancestors of everyone in the planet". Marean an colleagues published similar findings in other South African sites such as Blombos Cave suggesting that modern human behaviors emerged earlier that previously accepted. Maybe we must recognize that the "creative explosion" leading to modern human behavior happened at different times in different regions....(by the way, what's the meaning of "modern human behavior?)
If you want to learn more about Pinnacle Point, and the findings presented by Marean and colleagues, you can check a very entertaining link created by Scientific American.

The biological basis of gene therapy

The biological basis of gene therapy
Gene therapy is a rapidly growing field of medicine in which genes are introduced into the body to treat diseases. Genes control heredity and provide the basic biological code for determining a cell's specific functions. Gene therapy seeks to provide genes that correct or supplant the disease-controlling functions of cells that are not, in essence, doing their job. Somatic gene therapy introduces therapeutic genes at the tissue or cellular level to treat a specific individual. Germ-line gene therapy inserts genes into reproductive cells or possibly into embryos to correct genetic defects that could be passed on to future generations. Initially conceived as an approach for treating inherited diseases, like cystic fibrosis and Huntington's disease, the scope of potential gene therapies has grown to include treatments for cancers, arthritis, and infectious diseases. Although gene therapy testing in humans has advanced rapidly, many questions surround its use. For example, some scientists are concerned that the therapeutic genes themselves may cause disease. Others fear that germ-line gene therapy may be used to control human development in ways not connected with disease, like intelligence or appearance.

The biological basis of gene therapy

Gene therapy has grown out of the science of genetics or how heredity works. Scientists know that life begins in a cell, the basic building block of all multicellular organisms. Humans, for instance, are made up of trillions of cells, each performing a specific function. Within the cell's nucleus (the center part of a cell that regulates its chemical functions) are pairs of chromosomes. These threadlike structures are made up of a single molecule of DNA (deoxyribonucleic acid), which carries the blueprint of life in the form of codes, or genes, that determine inherited characteristics.

A DNA molecule looks like two ladders with one of the sides taken off both and then twisted around each other. The rungs of these ladders meet (resulting in a spiral staircase-like structure) and are called base pairs. Base pairs are made up of nitrogen molecules and arranged in specific sequences. Millions of these base pairs, or sequences, can make up a single gene, specifically defined as a segment of the chromosome and DNA that contains certain hereditary information. The gene, or combination of genes formed by these base pairs ultimately direct an organism's growth and characteristics through the production of certain chemicals, primarily proteins, which carry out most of the body's chemical functions and biological reactions.

Scientists have long known that alterations in genes present within cells can cause inherited diseases like cystic fibrosis, sickle-cell anemia, and hemophilia. Similarly, errors in the total number of chromosomes can cause conditions such as Down syndrome or Turner's syndrome. As the study of genetics advanced, however, scientists learned that an altered genetic sequence also can make people more susceptible to diseases, like atherosclerosis, cancer, and even schizophrenia. These diseases have a genetic component, but also are influenced by environmental factors (like diet and lifestyle). The objective of gene therapy is to treat diseases by introducing functional genes into the body to alter the cells involved in the disease process by either replacing missing genes or providing copies of functioning genes to replace nonfunctioning ones. The inserted genes can be naturally-occurring genes that produce the desired effect or may be genetically engineered (or altered) genes.

Scientists have known how to manipulate a gene's structure in the laboratory since the early 1970s through a process called gene splicing. The process involves removing a fragment of DNA containing the specific genetic sequence desired, then inserting it into the DNA of another gene. The resultant product is called recombinant DNA and the process is genetic engineering.

There are basically two types of gene therapy. Germ-line gene therapy introduces genes into reproductive cells (sperm and eggs) or someday possibly into embryos in hopes of correcting genetic abnormalities that could be passed on to future generations. Most of the current work in applying gene therapy, however, has been in the realm of somatic gene therapy. In this type of gene therapy, therapeutic genes are inserted into tissue or cells to produce a naturally occurring protein or substance that is lacking or not functioning correctly in an individual patient.

BIOTECHNOLOGY AND ENVIRONMENTAL BIOSAFETY

BIOTECHNOLOGY AND ENVIRONMENTAL BIOSAFETY

Genetical modification of Agricultural Seeds- cotton, soya, maize, potato, rice and trees in the forest.

Prologue

The all encompassing big macabre issue discussed world wide today is the invasion of the good science, ‘biotechnology’ to virtually every nook and corner of the biosphere and practically turned to the bad science, ‘thanotechnology’ for every living element of concern and speeding up the rate to total annihilation of the biosphere.It all began with a little known episode in 1980, that is the US Supreme Court decision in the case, Diamond vrs. Chakrabarty, where the highest US court decided that biological life was legally patentable.

History

Anand Mohan Chakrabraty a microbiologist and employee of General Electric Company (GE) developed a type of bacteria that could ingest oil from oil spills. GE rushed for a patent in 1971 which was turned down as life forms were not patentable. GE sued and won. In 1985 the US Patent and Trademark Office (PTO) ruled that the Chakrabraty ruling could be further extended to all plants, seeds and plant tissues or to the entire plant kingdom.

US company W.R. Grace was granted 50 US patents on the Indian Neem tree which even included patenting indigenous knowledge of medicinal use of the Neem products (since been leveled ‘biopiracy’). In 1988 PTO issued patent on animal to Harvard Professors, Philip Lader and Timothy A. Stewart who had created a transgenic mouse having genes of the chicken and human being. In 1991, PTO granted patent to human stem cells and later to human genes. Biocyte was awarded European patent on all umbilical cord cells from foetuses and new born babies even without the permission of the ‘donors’. European Patents Office (EPO) received applications from Baylor University for the patenting of women who had been genetically altered to produce GE proteins in their mammary glands.

Baylor University essentially sought monopoly rights over the use of human mammary glands to manufacture pharmaceuticals. Attempts also were made to patent blood cells of indigenous people of Panama, the Solomon Islands and Papua New Guinea. Within a decade the ‘Chakrabarty ruling’ of the US Supreme Court revolutionised the research and developments in biotechnology involving microbes to human beings which led it to be branded as bad science, “thanotechnology” in the following decade and hated world wide. biotech companies engaged in biotech pharmaceuticals quickly moved to agriculture, obtained patents on seeds, buying up small seed companies, destroying their seed stocks and replacing the same with GE seeds. In the last decade several companies have gained monopoly control over such seeds world wide as soy, corn and cotton ( used in processed foods via cotton seed oil). As a result, nearly 2/3 rd. of such processed foods showed some GM ingredient in them.

However, even without any labelings, the concerned US consumers were aware of such pervasive food products of biotech companies. Immediately the companies knew that aware citizen kept away from GM foods and they organized to convince the regulators not to require such labelings. Somewhat shockingly the bureaucratic risk evaluators in the US turned a blind eye towards the ill motives of the bio-tech companies.

The point of concern

All genetical modifications are based on recombinant DNA technology. The present society is faced with unprecedented problems not only in the history of science, but of all life on earth. The GE technology enables the profit oriented biotech companies the capacity to redesign the living organisms, the products of three billion years of evolution. In the words of Dr. George Wald, Nobel Laureate in Medicine (1967), Higgins Professor of Biology at the Harvard University, “potentially it could breed new animal and plant diseases, new sources of cancer and novel epidemics”.

On Record

In 1989, dozens of Americans died and over several thousands were afflicted and impaired owing to the ingestion of a genetically altered version of food supplement L – tryptophan. A settlement of $ 2 billion was paid by Showa Denko, Japan’s 3rd. largest chemical company (Mayeno and Gleich, 1994)

In 1996, pioneer Hi-Bred spliced Brazil nut genes into soy beans. Some individuals are so allergic to this nut that they go into apoplectic shock which can cause death. Animal tests confirmed the peril and the product was soon removed from the market before any fatalities occurred. In the words of Marion Nestle, HOD Nutrition, New York University, “the next case could be less than ideal and public less fortunate.”

In 1994 US Food and Drug Administration approved Monsanto's r-BGH, a GE growth hormone, for injecting the dairy cows to enhance their milk yield in spite of experts warning that the resultant increase of IGF-1, a potent chemical hormone, linked to 400 – 500 % higher risks of human breast, prostrate and colon cancer. According to Dr. Samuel Epstein of University of Chicago, “ it induces the malignant transformation of human breast epithelial cells.” Studies on Rats confirmed the suspicion and showed damage to internal organs with r-BGH ingestion. Even FDA’s own tests showed a spleen mass increase by 46%, a state that is a prelude to ‘leukemia’. The argument that the substance get damaged by pasteurization was nullified by 2 of Monsanto’s own scientists, Ted Elasser and Brian Mc Bride who found only 19% of the hormone get destroyed after 30 minutes of boiling (pasteurization takes only 30 seconds). Inspite of Canada, EU, Australia, New Zealand and even the UN’s Codex Alimentarius refusing to endorse the GE hormone, the same is freely marketed in the US by Monsanto. It was found out that 2 US bureaucrats namely, Margaret Miller and Micheal Taylor in the US FDA who helped Monsanto’s r-BGH pass the risk factor barrier were in fact earlier Monsanto employees.

Several other GM products approved by US FDA involve herbicides that are commonly known as ‘carcinogenic’, viz – ‘bromoxiny’l used on Bt. Cotton and Monsanto's ‘round-up’ or Glufosinate used on GM soy, corn and canola. Sharyn Martin, a researcher, has opined that a number of auto- immune diseases are enhanced by foreign DNA fragments which come with G M food that are not fully digested in the human stomach and intestine. These DNA fragments absorbed into the blood stream mix with normal DNA through recombination and are, hence, unpredictable. Such DNA fragments have been found to be in GM soy and other GM products available in the market.

The fear factor

Professor Joe Cummins, Professor Emeritus of Genetics, University of Western Ontario said, ‘ Virus resistant crops are becoming the mainstay of biotech industries. These crops carry foreign virus genes which are genetically engineered to empower the plants to resist virus attacks. Most of the fruits, vegetables and baby food marketed in the US are of this category. Lab. experiments have shown that ‘the GE viral genes in food potentially give rise to new viruses – deadlier than the viruses that the crops are being protected from’, a fact that is quite alarming.
In 1986, it was reported that GE plants having TMV genes delayed the development of the disease and this report opened the flood gates to create resistance to a range of other viruses. But the fact is that viral coat protein production in GE crop does not block the virus entering into the plant cell rather the transgene is exposed to the nucleic acids of many viruses that are brought to the plant by insect vectors. A number of study results are there to show that plant viruses can acquire a variety of viral genes from GE plants through recombination.

For examples-
* Defective Red Color Mosaic Virus lacks the gene enabling it to move from cell to cell and hence is not infectious ,but recombined with a copy of that gene in GE Nicotina benthamiana plants, regenerated the infectious RCMVirus.
* GE Brassica napus and Nicotiana bigelovii containing “ gene- vi ”, a
translational activator from the Cauliflower Mosaic Virus (CaMV) which
recombined with the complementary part of a virus missing that gene, and
produced new infectious virus in all GE plants.
* N. benthamiana expressing a segment of the Cowpea Chlorotic Mottle Virus (CCMV) coat protein gene recombined more frequently with the defective virus missing that gene.
* N. benthamiana was transformed with 3 different constructs containing coat protein coding sequence of African Cassava Mosaic Virus (ACMV). The transformed plants were inoculated with a coat protein deletion mutant of ACMV that induces mild systemic symptoms in control plants. Several such inoculated plants of the transgenic lines developed severe systemic symptoms typical of ACMV confirming recombination had occurred between mutant viral DNA and the integrated construct DNA resulting in the production of recombined viral progeny with ‘ wild type ’ virulency.

The CaMV recombination, when and where ?

CaMV 35 s promoter gene, is the ubiquitous viral sequence in all the transgenic (GM) plants which are either already commercially released in the market or undergoing field trials. This gene is needed by all GM plant producers because it drives the production of gene messages from the genes inserted to provide herbicide tolerance, insect- pest resistance, antibiotic resistance and a range of other functions deemed to improve the commercial quality of the crop plant. In the absence of this ‘promoter gene’, the ‘inserted gene’ remains inactive, while in its presence the gene activity is maintained at a high level in all of the plant tissues irrespective of the changing environmental conditions which drastically affect the activity of ‘promoters’ native to the crop plant.

The 2 events which occurred in 1999 provoked Professor Cummins and other independent scientists to draw global attention to such alarming industrial scientific maladies that may have disastrous consequences. In fact Professor Cummins had in 1994 questioned the environmental safety of the release of CaMV 35 s promoter gene through the GM plants. Experimental evidences available indicated that the frequency of genetic recombination of CaMV 35 s promoter gene was much higher than those of other viruses. When recombinant CCMV was recovered from 3% of transgenic N. benthamiana containing CCMV sequences, recombinant CaMV was recovered from 36% of transgenic N. begelovii.

Event -1. Scientists of John Innes Research Institute published a paper showing that the CaMV 35 s promoter has a recombination ‘hot spot’ meaning it is prone to break and reassociate with other pieces of genetic material, may be of other viruses.

Event- 2. Dr. Arpad Pusztai, a senior scientist working in the UK govt. funded Rowett Institute in Scotland was sacked from his job because he revealed the results of feeding experiments suggesting that transgenic potatoes were unsafe. The lab. Rats fed with GM food showed increased lymphocytes in gut lining indicating damage to intestine from non specific viral infection.

Scientists Mae- Wan Ho and Angel Ryan published a paper in October 1999 issue of Journal of Microbial Ecology in Health and Disease warning that the CaMV 35 s promoter is interchangeable with promoters of other plant and animal virus and is promiscuous and functions efficiently in all plants, green algae, yeast and E. coli. Its recombination hot spot is flanked by multiple motifs and is similar to other recombination hot spots such as that of the Agrobacterium –T DNA vector, the other most commonly used gene, in making transgenic plants. They also claimed to have demonstrated in the lab. of the recombination between viral transgenes and infecting viruses.

In an article published in the online journal of European Food Research and Technology (2006) authors ( Marit R. Myhre, et. al. ) claimed to have constructed expression vectors with CaMV 35 s promoter inserted in front of 2 ‘reporter genes’ encoding firefly luciferase and green fluorescent protein (GFP), respectively and performed transient transfection experiments in the human enterocyte – like cell line, Caco - 2 and found that the CaMV 35 s promoter genes drive the expressions of both the ‘reporter genes’ to significant levels.

A Major development into the cause of Brain Cancer in children

A Major development into the cause of Brain Cancer in children

A recent breakthrough from a study on paediatric brain cancer, may be the key to finding a cure, or at least much more effective treatment. The study, spearheaded by the Research Institute of the McGill University Health revealed a significant genetic difference between this type of cancer and the adult equivalent (Jeremy Schwartzentruber, 2012). Brain cancer is one of the deadliest of cancers in children, and the most common form of brain cancer, GBM multiforme has an average survival of only 12-17 months even with aggressive treatment. 

 As you may already know, cancer is a disease, which stems from damaged DNA, leading to uncontrolled cell division, and then tumours. Tumours, however, are not always cancerous, and are only malignant if they “invade nearby tissues and spread to other parts of the body” and may return even after being removed through surgical methods. (National Institutes of Health, 2012). Brain cancer is particularly life threatening as it is located in an essential organ of the body, which has limited space. The tumour in the brain may increase the intracranial pressure, which leads to headaches, vomiting, comas, and in children; large bulges in the fontanelles (soft spots which allow the skull flexibility to fit through the birth canal). Other symptoms of brain tumours include many neural dysfunctions ranging from impaired senses to changes in personality to epileptic seizures, which sadly can be explained by many other diseases, and brain cancer can be overlooked. (Charles Patrick Davis, 2012)

 This study sequenced the exomes of 48 children who had GBM and found two genetic mutations which accounted for up to 40% of the GBM in the sample (Science Daily, 2012). An exome is a specific area of the entire genome which are important the creation of particular types of proteins. This method is more efficient, as there are over 180,000 exons in the entire genome, and the “relevant” exons can be sequenced much faster and can detect variations or mutations much more successfully (Sarah B. Ng, 2009).


 Figure 1 MRI of a Glioblastoma multiforme (Eric M. Thompson, 2011)
 The two genetic mutations were:
1.     “Somatic mutations in the H3.3-ATRX-DAXX chromatin remodelling pathway in 44% of the tumours” (Jeremy Schwartzentruber, 2012)
2.     “Recurrent mutations in H3F3A, which lead to amino acid substitutions in critical parts of the histone tail in 31% of tumours” (Jeremy Schwartzentruber, 2012)

 According to Dr Jabado of the MUHC, it was not known why children and adolescent GBM patients did not respond to treatments as well as adult patients. The commonplace treatments of chemotherapy and radiotherapy had inexplicably been resisted by tumours in children, which were revealed by this study to be caused by the mutations preventing the treatments to properly target and differentiate cancerous cells from healthy cells. He continued to say that this results “(are) significant here … (as) the first time in humans we have identified a mutation in one of the most important genes that regulates and protects our genetic information. This is the irrefutable proof that our genome, if modified, can lead to cancer and probably other diseases.” (Science Daily, 2012)

This genetic mutation has been detected in other forms of cancer, and the researchers from MUHC are hopeful that this breakthrough will lead to new treatments for cancer in specific patients with these mutations (Hazell, 2012). Continued developments such as these will lead to the future of patient care, which will utilise personalised genome mapping and treatment plans based on the individual.

Genetics in Cancer

Genetics in Cancer

Hello, everyone. Today, I shall discuss the topic of cancer or, more accurately, a recent advance in genetics that should assist us greatly in the fight against cancer. Cancer currently afflicts 112,300 Australians, and causes 39,000 deaths every year (Australian Institute of Health and Welfare 2008). You can see that this is quite an intolerably large figure. Luckily, scientists are becoming able to identify the specific genetic mutations that lead to individual malignant neoplasms (that’s just the smart-people name for cancerous tumours). This innovation lets us give more effective treatment, and undergo greater in-depth analysis of the origins of a cancer.


The University of Colorado

This technique is still in the early stages of development, so scientists are not even close to identifying all of the genetic mutations that cause all types of cancer. However, researchers at the University of Colorado Cancer Centre performed a clinical trial in 2010 in which they did actually manage to link genetic anomalies to cancer. In this case, they studied a particular rearrangement of genes inside the cancer cells of thirteen different lung cancer patients. The study involved testing a drug designed to target this ‘gene rearrangement’ (Camidge 2010).

Diagram of human lungs containing a tumour

These researches managed to show that the identification of genetic mutations in cancer cells allows cancer to be treated very effectively. To see just how effective it is, you can look at the results of the trial for one of its patients, 60-year-old Ellen Pulhamus. Before the study, she had five malignant tumours, which shrunk by 62 percent after just six weeks! In addition to that, another round of treatment brought down their size by a further 50 percent! (Brown 2010) Results as fantastic as these mean that oncologists should soon be able to move on from prescribing drugs that will only work for about one in ten cancer patients, and charge forward to the stage where they can determine exactly which patients will benefit from which treatments, by looking at the genes of their tumours (Brown 2010).


Tumours in a lung


Another goal of the researchers in this field is to try to use gene identification to trace cancer cell mutation back to its origins. This could allow the primary prevention of some cancers by exposing the kinds of lifestyles and environmental conditions that lead to them (Brown 2010). It may even provide current cancer patients with some peace of mind, in that they could find out the reason or reasons behind them being so sick.




Cancer is a tragedy that most of us will have to experience at some point in our lives, whether it be through having to endure it ourselves or witness it in someone close to us. The work done by researchers like those at the University of Colorado Cancer Centre will allow us to extend, or even save, a considerable number of lives, from within our species and perhaps outside it. With cancer being the prevalent calamity that it is, such an achievement will have far-reaching positive consequences for our entire race.

Alcoholism - Is it a Genetic Mutation?

Alcoholism - Is it a Genetic Mutation?


Alcohol dependence, also known as alcoholism, is considered medically as a disease. Its symptoms, as listed by the American Association for Clinical Chemistry (2010), include increased tolerance, cravings, loss of control and physical dependence. For decades, sufferers of the disease have not only experienced its harsh physical and psychological effects, but also discrimination and stereotypes created by society. In recent years, however, scientific research has revealed that the likelihood of developing alcoholism is increased by the possession of variations in certain genes (Arbor 2011). When variation occurs in two specific genes, unc-79 and GABRA2, it is thought that it influences alcohol sensitivity (O’brien 2010) and impulsive behaviours (Arbor 2011).

 Gene mutations are permanent alterations to sequences of DNA sections of chromosomes (U.S. National Library of Medicine 2012). When mutations occur in genes, it can affect the cell or organism’s ability to function normal, therefore promoting alcoholism in humans.

The gene unc-79 in mice, as well as the human version of the gene, is a poorly understood gene thought to interact with a neuron called NALCN (O’Brien 2010). In studies with mice, the mice that possessed mutated unc-79 genes voluntarily chose alcohol over water when offered the two. The mutant mice also were highly more sensitive to the alcohol. When injected with pure ethanol, the mice blacked out for much longer than the non-mutant mice. These observations in mice are thought to arise from the unc-79 gene mutation, dubbed as Lightweight, altering the neuronal responses to alcohol governed by NALCN (O’Brien 2010).



The GABRA2 gene is responsible for the functioning of receptors in part of the mammalian brain called the insula (Arbor 2011). In a recent study, those with the variant GABRA2 gene demonstrated higher levels of impulsiveness when under distress, with high activation in the insula. This links to the idea humans, particularly females, turn to alcohol to relieve distress and anxiety (Arbor 2011).

Both unc-79 and GABRA2 gene variants are just some of the genes that contribute to the symptoms of alcoholism, but do not directly cause it. However, as alcoholics, their families and researchers attempt to discover its medical foundations, the discoveries of mutations in genes as alcoholism contributors is extremely significant for prevention, treatment and understanding of alcohol dependence.

DNA as a Data Storage Device

DNA as a Data Storage Device

In this day and age, we are all surrounded by technology, with gadgets and gizmos such as CDs, iPods, phones, computers, USBs – all driving us towards the ongoing quest for new and better ways to store information. With the past few years, scientists have been investigating every possibility, ranging from semiconductors to carbon “nanoballs” to even our very own DNA!
Deoxyribonucleic acid, or DNA, possesses many ideal characteristics of a data storage device for the future. Present in all living organisms, a key feature of DNA is its capacity to store significantly large amounts of information in its nucleotide sequences. The structure of a nucleotide consists of a sugar-phosphate backbone, attached to one of the four nitrogenous bases – Adenine, Thymine, Cytosine and Guanine.
Figure 1: The structure of a nucleotide, consisting of a phosphate group, deoxyribose (sugar) and a nitrogenous base.

Using genome sequencing, these nucleotides can be connected to form synthetic oligonucleotide sequences containing data stored in the form of specifically ordered nitrogenous bases.
In a recent study conducted by Yachie et al. (2007) at Keio University, the practicality of using bacterial DNA for long-term, large-volume data storage was investigated. The researchers were able to store a short, alphanumeric message in the loci of a Bacillus subtilis genome and retrieve it successfully. To do so, their chosen message “E=mc2” was firstly translated into dinucleotides, using a 4-bit binary code encryption key.
Figure 2: Encryption keys used in the Yachie et. al (2007) study at Keio University, Japan.

These dinucleotides were then used to form long sequences that were then injected into the Bacillus subtilis cells. After an overnight incubation period, the data was then recovered.
Figure 3: The 4-bit binary codes translate into dinucleotides which make up synthetic oligonucleotide sequences.

 The most common data storage and recovery method for DNA is based on polymerase chain reaction (PCR), which involves the use of primers to amplify the coded regions of DNA. Encryption keys are then employed to decode each dinucleotide into its corresponding bit code and if necessary, into alphanumeric code for convenient use or interpretation.
Figure 4: Bacillus subtilis under a microscopic.

Not only can DNA significantly more bytes than our currently existing mechanisms, but it is also praised for its extreme durability in long-term data storage. Naturally, DNA is passed down from generation to generation of living organisms, and because of this, scientists postulate that any data inserted in an organism’s genome will last as long as the line of the host organism, which is often hundreds of thousands of years. 
However, if the organism undergoes genetic evolution or adaptation, there are several problems that may occur, including data transmutation or loss. Several methods have been suggested to reduce the effect of these mutation rates, such as the selection of a robust host organism that can survive in harsh environments. In addition, the study by Yachie et al. (2007) suggests storing the data in an “alignment-based” method, where several back-ups of the data are also inserted with the original information to increase the stability of DNA data and reduce the chances of data deletion.
The phenomenon of using genomic DNA to archive information is considered as a significant advancement in genetics. According to recent studies, the natural characteristics of DNA, such as compactness, heritability and durability construct it as an ideal data storage device – which may ultimately blur the line between nature and technology forever.

Can't stop eating? Blame it on your genes

Can't stop eating? Blame it on your genes

Obesity is a medical condition where excess body fat accumulates to the extent of causing adverse effect on health which may lead to reduced life expectancy with increased health problems. It increases the likelihood of different diseases especially the heart disease, cancer as well as type two diabetes. Obesity tends to run in families. Weights of adults selected during studies reveal that their weights are closer to their biological parents’ weights.
A recent study done by Guey-Ying Liao and his colleagues (2012) suggests that human obesity may possibly be caused by mutations in the Bdnf gene as it produces transcripts having either short or long 3’ un translated regions (3’ UTRs). However, in regulation of energy balance, the precise role of brain-derived neurotrophic factor (BDNF) is unknown. The relationship between Bdnf mRNA with along 3’ UTR which means long 3’ UTR Bdnf mRNA, leptin neural activation and the body weight is shown. Long 3’ UTR Bdnf mRNA has been found to be enriched in dendrites of hypothalamic neurons. It has also been found that insulin and leptin could possibly stimulate its translation in dendrites.
Mice harboring a truncated long Bdnf 3’ UTR furthermore developed acute hyperphagic obesity. However, this was completely reversed by viral expression of somewhat long 3’ UTR Bdnf mRNA found in the hypothalamus. The ability of leptin in activating hypothalamic neurons and inhibiting food intake was compromised despite the presence of leptin receptors, in the mice. The results obtained revealed a novel mechanism which linked leptin action to BDNF expression happening during hypothalamic mediated body weight regulation and this also implicated dentritic protein synthesis in the process.
Researchers claim to have found a single mutant gene is the one to blame for the inability of brain to tell obese people when to stop eating. The brain derived neurotrophic factor in mice either stops or slows passage of leptin as well as the insulin signals through the brain. In the humans the aforementioned hormones are released at somewhere at the time when one can see the bottom of the colonel’s sixteen piece bucket. It is not usually the guiltiness that tells one to stop but the brain dictates when the climax is reached. In cases where the signals fail to reach the locations that are of concern in the area in brain signaling satiety.
Such discovery may possibly open up novel strategies which help the brain control body weight. The Bdnf does not only control body weight, but notably in failure to development of one of Bdnf gene, there is a flow effect resulting in deficits in learning and memory in mice. Neurons rarely talk to each other in case there is a problem with Bdnf gene and as such, the leptin and insulin signals become effective without modification of appetite. Faulty transmission line can be repaired by the strategy where missing Bdnf would be produced using virus based gene therapy despite the difficult of delivering across the brain blood barrier.
 

The lack of a single gene has been found to cause obesity. Leptin appears linked to human disease in which case several childhood diseases have been associated with mutations in leptin genes. Leptin however plays a big role in the body of human beings today. As an issue of concern in human science, research findings should be well administered so as to ensure that the risks of obesity associated with gene mutations are effectively curbed.

Epigenetics in the Ice Age

Epigenetics in the Ice Age


Recent research highlighted by the New Scientist article “Fossil DNA has clues to surviving rapid climate change” suggests that epigenetics played a significant role in the adaptions animals made during the last ice age. It focussed on research by a team from the University of Adelaide and University of New South Wales, headed by Alan Cooper and Catherine Suter, who made the discovery after investigating the genetic sequence found in some specimens of extinct bison (Holmes 2012).


Epigenetic inheritance involves the inheritance of characteristics from one generation to another, by processes that do not involve the nucleotide sequence of DNA (Reece et al, 2011, p. 364). Therefore, Cooper and Suter’s team looked at the characteristics that animals developed, which may have been passed down to future generations, when the animals were exposed to the change in environment. This was done by finding the bones of a bison that lived around 26,000 years ago in the Canadian arctic permafrost (Figure 1), before extracting the DNA contained within these bones (Holmes 2012). Tests were then performed, using the bisulfate sequencing technique, searching for DNA methylation (Holmes 2012). DNA methylation is when a methyl group joins to a base of DNA, commonly cytosine (Reece et al, 2011, p. 364) (Figure 2). According to the website Sigma-Aldrich, “DNA methylation is an epigenetic modification that changes the appearance and structure of DNA without altering its sequence” (2008). Further research completed by the team of scientists proved that some of the DNA methylations they found in the bison were in the same places of modern cow DNA (Holmes 2012). This discovery is very important, as it shows that there was some form of epigenetics during the time period that the fossils lived. As for the similar methylations that were discovered in modern cows, Holmes suggests that this “is strong evidence that the ancient methylations were not the product of chemical damage occurring after the bison’s death” (2012). More tests on five other specimens of bison found gave the scientists no results (Holmes 2012), which proves that this area of research is very difficult. Noting that scientists currently have limited knowledge when it comes to understanding epigenetic signals (Holmes 2012), advances in this field are hard to make. There are a number of different techniques scientists can use to tell if epigenetic modification has occurred, like bisulfate sequencing, fluorescent insitu hybridisation and DNA adenine methyltransferase identification for example (Medindia, n.d.). Despite this, far more research is required to understand what that information is saying, and to get anything out of it.

 There is still a lot of work to be done on this before any major conclusions can be drawn. But this research has found that at the start of the last ice age, animals may have undergone epigenetic change to adapt to the changing environment. With the current climate change situation facing humans, this find in the remains of a 26,000-year-old bison could be important in the future.

Eye Colour in Humans – Not Just a One Gene Affair

Eye Colour in Humans – Not Just a One Gene Affair

Contrary to popular belief eye colour in humans is not just controlled by one gene in our DNA. High school biology teaches us about Gregor Mendel and his theories about inheritance patterns and how they relate to human eye colour. Prior to recent studies conducted into the genetics of eye colour it was thought to be a strictly mendelian trait (White and Rabago-Smith). However it is now known to be the product of multiple genes. This theory is used to explain why eye colour does not comply with Mendelian patterns of inheritance. For example blue-eyed parents are able to have brown-eyed children, which should not be possible in a Mendelian model where brown is dominant over blue (which can only occur with homozygous recessive genes and thus they would not be able to pass on the dominant gene to their offspring).  This model using a single gene is unable to explain the spectrum of eye colour and the fact that eye colour in humans shows both incomplete dominance and epistasis (University of Queensland).  This suggests that there is more than one gene that controls eye colour.


The colour of an individual’s eye is determined by the ratio of two pigments in the iris of their eye. These two pigments are called eumelanin (the yellow pigment) and phenomelanin (the black pigment) (White and Rabago-Smith). These pigments, melanin, and are produced in the melanocytes of your eye (Ibid). Blue eyes arise from low levels of melanin and increasing levels produce the rest of the eye colour spectrum (Stanford University). The amount of melanin in the iris also affects eye colour. The more melanin that is present, the darker the apparent colour of the eye as when light enters the eye it is largely absorbed rather than reflected back as colour (White and Rabago-Smith). So people with lighter eyes have less melanin than people with darker shades. Individuals may have red or violet eyes; this is due to a condition called ocular albinism and is caused by mutations in their gene sequence (Ibid). 

 Studies conducted by various institutions including the Institute for Molecular Bioscience at the University of Queensland have shown that there are 16 genes which affect eye colour (Ibid). However most of these genes have only a small effect, the two major genes are HERC2 and OCA2 (Ibid). HERC2 affects the way in which the code of OCA2 is expressed in the DNA sequence because of its position in the DNA (Ibid). Any changes in the sequence of these genes have large impacts on the eye colour of the individual. Changes in the OCA2 gene been shown to account for around 74% of variation in eye colour (Duffy, Montgomery and Chen; White and Rabago-Smith). If both copies of the OCA2 gene are missing it leads to ocular albinism (White and Rabago-Smith). Other genes which effect eye colour include agouti signalling protein, tyrosinase, membrane associated transporter protein, p protein oculocutaneous albinism II and melanocortin 1 receptor (Ibid).

 It is clear from the research that has been conducted in this area that the Mendelian model of inheritance is unable to explain the expression of eye colour in humans. There are multiple genes responsible for melanin production in the eye and the main two are HERC2 and OCA2 (Tyler).

Genetic Testing for Newborn Hearing Loss

Genetic Testing For Newborn Hearing Loss


As modern technology allows rapid progress in the field of genetics, genetic testing for various disorders is becoming increasingly common. One recent development in this area is genetic testing for a form of congenital hearing loss.

Currently, newborn hearing screening programs are in place in many countries to test all infants for hearing abnormalities. However, this in itself does not produce a diagnosis for newborns who fail the tests, and indeed most of them have to wait up to three months before any diagnostic evaluation is started. This is not in the best interests of the child, as evidence shows that “identification and habilitation of deaf infants before six months of age improves language outcomes.” (Schimmenti, et al., 2011)


Almost half of all infants with congenital hearing loss have underlying genetic causes for their condition. It has recently been identified that the most prevalent of these are mutations of the Gap Junction Beta-2 gene (GJB2). (Schimmenti, et al., 2011) GJB2 is responsible for directing the synthesis of Connexin 26, a protein that helps to create gap junctions in the cochlea through which potassium ions can flow, thus having an important role in the homeostatic regulation of potassium in this area. This process is essential for maintaining appropriate levels of potassium in the inner ear and thus preventing the malfunction and damage of cells vital for hearing. Connexion 26 may also play an important role in the maturation of certain cochlear cells. More than 90 mutations of the GJB2 gene have been identified thus far that produce a non-functional Connexin 26 protein and result in congenital hearing loss.  (Palmer & Boudreault)


All of these mutations studied to date are autosomal recessively inherited, however it is known that autosomal dominant mutations also exist. Of the afore-mentioned mutations, the majority exert their effects by deleting base pairs. This changes the sequence of amino acids produced and leads to the manufacture of a misshapen and unstable Connexin 26 protein.

Fortunately, a genetic test for the most common of these base pair deletion mutations has recently been derived. Blood samples can be taken from newborns and the appropriate segment of DNA isolated and amplified through PCR then sequenced using this genetic test to determine if the mutation is present. This test has been experimentally proven to detect the majority of infants with GJB2-related hearing loss amongst those that fail hearing screening tests. (Schimmenti, et al., 2011)

Schimmenti et al. (2011) believe that these genetic testing results could be available before traditional diagnostic testing begins and so would lead to an earlier diagnosis and therefore better speech and learning outcomes for many individuals. It is also anticipated that further genetic testing for many other hearing loss-associated mutations of this gene will become available in the near future. Considering that GJB2-related hearing loss is accountable for the majority of genetic hearing loss (and genetic conditions cause half of all deafness), undertaking genetic testing for mutations in this gene may therefore be very worthwhile. This process would involve taking a small blood sample from newborns who fail the hearing screening tests and analysing it for the presence of a mutated GBJ2 gene.

A Healthy Mind is a Healthy Body

A Healthy Mind is a Healthy Body

The world of genetics has evolved into new heights with the invention of personal genomics. This new technology allows practitioners to gather accurate data about a persons health status, which comes in handy when prescribing medication or preventing disease. Eric Nelson, a writer in the Washington Times, explains how a new company, Navigenics, can help you over come your worst health problems and perhaps even increase your life expectancy. This allows us to ask the question: Is there a definite link between the “mind” and the “body”? Questions like what is personal genomics; how does personal genomics work; and what sorts of benefits come with personal genomics, shall all be answered in this blog.

 So what is personal genomics you might say? Well personal genomics is basically the practice of reading or encrypting genetic codes, which tell us about a person’s life style (Nelson, 2012). By reading a persons genes, practitioners in this field can accurately pin point “faults” or “disorders” occurring in your body’s systems and hopefully can rearrange the persons life style in order to prevent such occurrences (Massachusetts General Hospital, 2008). Examples of changing a persons life style are changing a persons diet, exercising more or changing occupation due to too high stress levels (Nelson, 2012). 


So how does personal genomics work exactly? Well a study is the Massachusetts General Hospital in 2008, indicated that there was a direct link between the mind and body (Massachusetts General Hospital, 2008).  This study looked at a wide range of people, all with different life styles (Massachusetts General Hospital, 2008).  The study looked at the specific genetics codes of each individual and it was found that the people with the bad life styles, (ie: people who did not exercise much, ate the wrong sort of foods and people who had problems with coping with stress), were the ones who illustrated cell inflammation, increased programmed cell death and changes to how the cell deals with free radicals (Massachusetts General Hospital, 2008). It can therefore be concluded that a change in diet, increase in exercise and coping with stress levels all have an impact on the health of your mind and body (Massachusetts General Hospital, 2008).

So what benefits come with personal genomics? Well as stated in the study, a person who is concerned about there health can visit a health professional and get tested for all sorts of diseases and/or problems occurring in there body (Nelson, 2012). This new power of genetics can then be used to either prevent or treat diseases that the person could have (Nelson, 2012). Therefore the link between the mind and body is very important when looking at the overall health of the person (Nelson, 2012).

Inheritance of Male Pattern Baldness

Inheritance of Male Pattern Baldness

What is Male Pattern Baldness (MPB)?

Male pattern baldness (MPB) is a condition which most men (and some women) will face during their lives. MPB causes in people a receding hair line and their hair will become a lot thinner. In the later stages of MPB complete baldness around the crown and possibly the middle section of the top of the head can occur. But what causes male pattern baldness?

What causes MPB?

Testosterone is a steroid hormone that affects many different areas of the body and their functions, however it is not often realized that testosterone is also the cause of hair loss. When testosterone is in the presence of an enzyme called 5-alpha-reductase, the enzyme will break down testosterone into dihydrotestosterone, which is often referred to as DHT.

Male pattern baldness occurs as a result of hair follicles being sensitive to DHT. If a hair follicle is sensitive to DHT it will miniaturize and eventually no hair will grow where that hair follicle grew. It can be seen that through the process of miniaturizing and loss of hair how the symptoms of MPB are so (Receding hair line, thinning of hair). (WebMD 2010)

How does a person’s genetics affect their chance of having MPB?
In 2005, German researches discovered a gene on the X-chromosome that affects baldness (Dr Barry Starr 2006). This gene (androgen-receptor gene, AR) instructs the making of androgen-receptors (also known as dihydrotestosterone receptors).   If the AR gene allows too many androgen-receptors to be made in the scalp or in hair follicles it can result in more testosterone being on the scalp. This in turn results in the creation of more dihydrotestosterone which then leads to greater loss of hair.

Some people who have MPB have an AR gene that performs normally. This means the AR gene is not the only factor that influences the development of MPB. Two independent studies were conducted to discover a common factor that people with MPB had that people without MPB did not have. Both studies came to the conclusion that people suffering with MPB have changes on their chromosome 20 compared to those without MPB.
Everyone has two chromosome 20s, one from each parent. This allows for one chromosome 20 to be unchanged even though the other is changed. This shows that there are three different combinations of chromosome 20s a person can have (and therefore three different likelihoods of having MPB):

1.       Two unchanged chromosome 20s (0 times more likely to develop MPB)
2.       One unchanged and one changed chromosome 20 (3.7 times more likely to develop MPB)
3.       Two changed chromosome 20s (6.1 times more likely to develop MPB)
(Melinda Beck 2008)

Not just one factor affects the likeliness of developing male pattern baldness.  An AR gene that allows for too many androgen-receptors to be in the scalp or hair follicles will increase the chances of developing MPB dramatically. Certain variations to the chromosome 20 also increase the probability of having MPB. Variations on one chromosome 20 will increase the chance of having MPB by 3.7 times and having variations on both chromosome 20s will increase the chance by 6.1 times.

A Cure For Obesity

A Cure For Obesity

Obesity is a major health concern all over the world. It can activate many other diseases including diabetes. Obesity is defined by the increased body weight caused by excessive accumulation of fat and the latest data recorded estimates that there are at least 300 million obese people in the world . Scientific researchers are constantly searching for efficient and effective ways to help reduce the risk of obesity. It wasn’t until recently that new research from the University of California, San Francisco suggested that ordinary fat cells can be reengineered to burn calories.
Image 1: Image of white fat cells.

Image 2: A scanning electron micrograph of
brown fat tissue .

Basically we have two different kinds of fat cells; white fat cells that store excess energy and, accumulate when weight is gained and brown fat cells which oxidize fuels and dissipate energy in the form of heat. Brown fat cells are the main interest, as experiments have shown they have the potential to counteract obesity. However these brown fat cells exist only in large doses in mice and infants. Adult humans do not have distinct brown fat, but they do appear to have small numbers of brown fat cells in white fat. So therefore to reduce the risk of obesity our bodies need to contain a larger amount of brown fat. Recently while investigating how a common drug given to people with diabetes works in mice, the University of California, San Francisco discovered a protein called PRDM16; found in both men and mice, can throw a switch on fat cells converting them from ordinary calorie-storing white fat cells into calorie-burning brown fat cells . This protein, PRDM16 also is encoded by a gene known as the zinc finger transcription factor that mediates protein-to-protein interactions . This protein can therefore assist the body in converting stubborn white fat cells into active brown fat. However to successfully complete this transition, the protein needs to be stabilized by a safe compound that enables PRDM16 to accumulate and activate receptors that induce brown fat cells before the protein breaks down .



Several experiments have been in place over the past few years to test this theory. As mentioned earlier mice contain large amounts of brown fat and therefore made the perfect test subjects. In the laboratory research, obese, male mice aged 3-4 weeks were injected with many types of drugs that had the potential to raise PRDM16 levels and therefore stabilizing the protein to promote the conversion of white fat cells into brown fat cells . One of the most effective drugs proven was the irisin hormone and within 10 days of treatment, the rodents’ blood sugar and insulin levels stabilized; preventing the onset of diabetes and they lost weight .

These experiments have not yet been tested on humans, however given that the mouse and human forms of the protein PRDM16 are quite similar there is a possibility that these same results will occur in humans; therefore will counteract obesity . The irisin hormone however being effective on mice still may have the possibility to prove ineffective on humans and therefore scientists are continually researching new drugs that target PRDM16 protein to raise and stabilize its levels and therefore offering new hope in the fight against obesity.

Genetic Information Provides Hope for Future in Treating Psychiatric Illnesses

Genetic Information Provides Hope for Future in Treating Psychiatric Illnesses

Genetics play a key role in the causation, development and heritability of many forms of diseases and disorders (Reece, 2011). Unfortunately, advancements in studies relating genomics to psychiatric illnesses have been slow in the past. This is due to the difficulty in identifying genes that contribute to such diseases. However, recent studies on a particular gene have revealed its connection with numerous psychiatric illnesses including ADHD, schizophrenia and autism (Ross RG, 2012).


The genetic component of diseases is associated with mutations of the gene which may induce an effect on the risk of developing illnesses (Reece, 2011). In the case of common non-psychiatric diseases, the risk of developing them can be linked to common variations of a few mutated genes that can be thoroughly analysed (which it has been). However, in the case of psychiatric diseases, it is a different story. A genome-wide association study (International Schizophrenia Consortium et al, 2009) produced novel results suggesting that psychiatric disorders are potentially affected by not a few, but thousands of gene variants, each having only a minute contribution to the disorder.
So how do researchers determine what genes are associated with psychiatric disorders if each gene has only a small effect? The method involves examining large alterations in the DNA nucleotide sequences which are replicated throughout the genome. These large alterations consist of DNA segments that are either missing or duplicated in the sequence. Because the number of altered segments varies as DNA is replicated, the genes are termed copy number variants (Henrichsen CN, 2009).



As genes are involved with many molecular activities such as protein synthesis, studying copy number variants (mutations in genes) is made simpler by recognising abnormal genetic activity.
Research conducted by Williams et al (2012) on 896 children with ADHD showed that the genome of those affected by ADHD exhibited a greater amount of copy number variants. Among the duplications of altered genes was the CHRNA7 gene, which encodes a7 nicotinic receptors. These receptors are crucial in the nervous system and are involved in many mental functions (Mazurov, 2006). Therefore, duplications of the CHRNA7 gene affects a7 nicotinic receptors, which in turn affect cognitive functions and ultimately lead to increased risk of ADHD, schizophrenia and possibly many other psychiatric illnesses.

 This association was further reinforced as four subsequent studies of subjects from the United Kingdom, United States and Canada all demonstrated similiar results – the amount of duplications of CHRNA7 and other copy number variants was greater in the genomes of those affected by ADHD (Williams et al, 2012).
Although the results of current studies (International Schizophrenia Consortium et al and Williams et al) do not have major contributions towards pharmaceutical or therapeutical developments, they are nevertheless fundamental and crucial to successive research. And the hope is that the findings of genetic information will lead to further studies in identifying more genes involved in and developing medicinal solutions for treating psychiatric illnesses.

How Genes Affect the Alcohol Use of Adolescents

How Genes Affect the Alcohol Use of Adolescents

Binge drinking and alcohol abuse is known to be a regular habit for many adolescents. According to the Australian Medical Association (2009), 39.2% of Australian adolescents (aged 14-19) reported acts of binge drinking in 2007. As such, studying the science of why binge drinking occurs is particularly relevant to today’s society. Through many previous scientific studies it has been found that this behaviour is related to genes. In more recent studies however, scientists have been able to determine which specific genotypes relate to these dangerous drinking habits. For example, some previous studies found that the genotypes hypothesised as relevant to alcohol consumption, the SLC6A4 neurotransmitter transporter and the DRD2 dopamine receptor, affected alcohol use whereas other previous studies found evidence contradicting these results. This blog aims to provide information on the recent scientific paper by Van der Zwaluw et al. (2011) which studied these genotypes alongside adolescent drinking motives and in particular, drinking to cope, to further examine the relationship between genetics and alcohol use.

An important factor in adolescent drinking behaviours is their drinking motives. The motives found to be related to adolescent’s drinking were enhancement, social, conformity and coping motives. Those who drank to cope were found to be more responsive to stress and have higher levels of problematic alcohol use than those who drank for any other reason. Van der Zwaluw et al. (2011) studied these drinking motives to compare the effect they have on alcohol use compared to the genotypes, SLC6A4 and DRD2.

 Both of the studied genotypes, SLC6A4 and DRD2, have functions which relate to emotions and feelings. The SLC6A4 genotype has been previously linked to anxiety, depression and other disorders whilst the DRD2 genotype’s function is to control the body’s emotions and positive reinforcement. By studying the functions and different variants of these genotypes, scientists have been able to find a theoretical link between specific variants of the DRD2 and SLC6A4 genotypes and alcohol consumption.

 The recent study by Van der Zwaluw et al. (2011) found that there was no significant relationship between alcohol consumption and the SLC6A4 and DRD2 genotypes. Hence, this recent study contradicts previous studies and the theoretical link between these genotypes and alcohol consumption. However, by also studying the drinking motives of the adolescents, it was found that drinking to cope did significantly affect alcohol use and was linked to alcohol-related problems. This link between drinking to cope and alcohol-related problems in adolescents was increased by the DRD2 genotype. As such, the DRD2 genotype did affect alcohol use but only for specific drinking motives. These findings demonstrate that alcohol use is more affected by drinking motives, such as drinking to cope, than it is by these specific genotypes. Therefore, it can be concluded that, until future research is conducted, there is no significant and direct relationship between genes and alcohol use.

The Disappearing Y Chromosome

The Disappearing Y Chromosome

 The size of the human Y chromosome is only a fraction of what it used to be. Once it was homologous to the X chromosome, but it now contains only 45 out of the 1700 genes it used to have[1]. Based on previous studies and assuming a linear rate of decay, it is expected that the human Y chromosome will disappear in roughly 4.6 million years.

 Does this mean the end of males? Not quite.

 A degenerating sex chromosome seems to be the norm of genetically determined sex[2]. In fact, organisms exist where the male chromosome is completely lacking, supporting the theory of the disappearing Y chromosome[2]. However, a study conducted by Hughes et al. provides new evidence on why the Y chromosome to stay for much, much longer.

 The male specific region of the Y chromosome (MSY) is not capable of genetic recombination with the X chromosome. Without genetic recombination, there are fewer mechanisms for genetic repair, leading to higher rates of mutations, deletions and insertions, all this, pointing to the inevitable degeneration of the Y chromosome.

 Hughes et al. argues that the human Y chromosome has reached stability, where it will not degrade further, by sequencing the genomes of the rhesus macaque and comparing it to that of the chimpanzee and human genome. The study focused on the MSY, identifying five distinct regions or “strata” based on its degree of similarity to the X chromosome.

 Comparison between the macaque MSY and the human MSY revealed that they share the same 18 ancestral genes in strata 1 to 4, indicating that their last common ancestor shared the same genes and that there was no subsequent loss of these genes after the human and macaque lineages diverged 25 million years ago. In strata 5 all species showed significant gene loss, losing 5 ancestral genes (4 for macaque) over the past 30 million years. However, the same genes are found on the human and chimpanzee MSY, indicating that this region has stabilised prior to the human/chimpanzee split.



 The findings of this study contradict the linear model for the degeneration of the Y chromosome as they fail to explain the relative stability of the human MSY genes over the past 25 million years. The results suggest an exponential decay with a baseline constant which extends the lifespan of the human Y chromosome indefinitely into the future.