Schizophrenia: a disrupted mind

Schizophrenia is a complex disorder that occurs in around 1% of adults. It is characterized by disordered thinking and speech, hallucinations, paranoid delusions and impairments of perception of reality.

It has generally been assumed that Schizophrenia would be caused by mutations in a very specific cluster of genes or even from high frequency genetic mutations, although scientists have never really had a full understanding of the role of genetics or environmental factors in causing it, until now.

Researchers looking at the DNA of people with schizophrenia compared to that of people without the disorder found more deletions and duplications across the sequence. Healthy people were found to only have 5% of the deletions and duplications present, while those with the disorder had them present in 15%. These disrupted genes are often essential in pathways leading towards normal brain development, and can effect neuronal growth and communication.

So instead of having one particular set of genes in which mutation causes schizophrenia, it is a case of any number of a few hundred or so genes that could mutate to cause it. And for different people these mutations occur in no particular genes, it’s just an overall increase in DNA mutation rates.

More info:
http://www.abc.net.au/science/articles/2008/03/28/2201595.htm?site=science&topic=latest

By Tom Beioley
41219711

Osteoporosis gene breakthrough

Two scientific teams in Iceland and the UK have independently discovered gene mutations that are linked to osteoporosis, a disease that leads to the weakening of bones. These mutations were found by using the DNA samples of thousands of women, both with the disease and without. These were screened for single nucleotide polymorphisms (SNPs), a type of random mutation. Two mutations particular were found which, if a woman had both, increases the risk of bone fractures by up to 30% and the risk of osteoporosis by up to 50%.

The first mutation is located on the LRP5 gene. This gene produces lipoprotein-receptor-related protein, which is a molecule on osteoclast cells which influences if the cell matures into a bone cell or not. This mutation increases the risk of osteoporosis or related fractures by 30%.

The second important mutation is found on the TNFRSF11B gene. This gene generates osteoprotegerin, which is a signalling molecule which blocks bone resorption. The mutation results in lower bone mineral density and therefore carriers are 20% more likely to experience bone fractures.

The discovery of these mutations is an important step towards the prevention of osteoporosis and the development of drug treatments. Women could be screened for the gene mutations and consequently change their lifestyle at an earlier age in order to aid in the prevention of developing the disease.

By Alice Adams
Related links:
http://www.newscientist.com/channel/life/genetics/dn13808-gene-discoveries-could-crack-bone-disease.html

Pedigree Analysis, Albinism

Albino is one of the disease affected by autosomal recessive.
There are several kinds of modes of heritance such as Autosomal dominant and recessive, X-linked dominant and recessive. Each modes of heritance has different traits and some disease occur because of the traits.

Albino is one of example for Autosomal recessive and tt is quite famous in the world. There are several kinds of disease in albino but main character of these diseases is luck of pigmentation of the skin and the hair either completely or partially. Dr Bossy found that mutations in genes that regulate the multi step process of melanin synthesis, distribution of pigment by the melanocyte, and/or melanosome biogenesis are the basis for these diseases. It is hard to live for animal with albino because of white colour being found out from predators easily. For human beings, because of luck of pigmentation of the skin, the rate of skin cancer is really high. People with albino must use sun cream but it is not possible to avoid sunburn with only using sun cream in some region such as Africa.

Like albino, there are lots of disease affected by atosomal dominant and recessive and X-linked dominant and recessive.

The souce is from http://www.emedicine.com/derm/topic12.htm

Research into regulation of gene expression in fruit flies: Implications for AIDS

Several scientists have presented the first detailed map of how the building blocks of chromosomes, condensed areas of genes and DNA, are organised in the fruit fly Drosophila melanogaster. They have managed to identify a critical stop sign for transcription of genes. This work could lead to better understanding of how diseases, especially AIDS, regulate its genes.
In the fruit flies, the researchers found that nucleosomes, proteins which DNA is coiled around, occur at certain locations on genes which are being transcribed. RNA polymerase, the enzyme which reads the DNA strand, is stopped by the first nucleosome and it remains there until chemical signals from the cell cause the removal of the nucleosome and cue the RNA polymerase to continue. So nucleosomes are barriers for transcription and therefore the impact of nucleosome organisation on RNA polymerase can now be seen.
Using state of the art ChIP-sequencing, a genome mapping tool, researchers were able to map the locations of hundreds of thousands of nucleosomes. The researches then compared the fruit fly maps to earlier maps of the baker’s yeast Saccharomyces cerevisiae. This showed that evolution has organised nucleosomes differently in more complex organisms such as the fruit fly compared to simpler life forms like the baker’s yeast.
In the nucleosome organisation of the baker’s yeast the nucleosome sit on top of the transcription starting sites. This means that the nucleosome must be contended with before the RNA polymerase can start transcribing. In the fruit fly the nucleosome is further downstream, which allows the RNA polymerase to start transcribing until it reaches the nucleosome where it is paused. The RNA polymerase will stay idle until chemical signals from the cell cause the removal of the nucleosome from its path and encourage the RNA polymerase to continue transcribing. It has become known over the last year that the fruit fly has 1000 genes which work in this way and the researchers expect there are even more of these genes in humans.
HIV genes have paused RNA polymerase and releasing the pause may be key to activating HIV replication of otherwise dormant viruses. Better knowledge of how gene expression is regulated can lead to better understanding of most human diseases and development of new more effective anti-viral drugs and this research is another step towards completely understanding the regulation of gene expression.
For more info:http://www.sciencedaily.com­ /releases/2008/05/080508103623.htm

Penn State (2008, May 9). Key Roadblock To Gene Expression Identified: Implications For AIDS. ScienceDaily. Retrieved May 12, 2008, from http://www.sciencedaily.com­ /releases/2008/05/080508103623.htm

Treatments and Progression of AIDS : Why is it different between patients?

Acquired immune deficiency syndrome or acquired immunodeficiency syndrome (AIDS or Aids) is a type of disease caused by HIV virus. A HIV patient shows many symptoms and infections as a result of body immune system damage. Within years, it will progressively deteriorates the body with more opportunistic infections and tumours as the body is left more and more vulnerable.

The use of genetic testing is now widely used to determine why HIV virus attacks people differently. Some example questions brought up by scientists are why is there only one person infected with the disease if there are two of them exposed to the virus, and if both are infected with HIV virus, why is that one show symptoms within two years but another only shows after decades later?

One discovery that has been recently reported regarding genetics and HIV is the number of copies of a normal human gene, CCL3L1, which encodes the protein MIP-1 a P. On average across population, each person possesses 2 copies of this gene, even though there are people having seven or more copies if this gene in their chromosomes. Research result has concluded that people with fewer copies of this gene have a higher risk of HIV virus attack. And among those who are infected, patients with fewer copies also develop more rapid progression of AIDS. Researchers also noted that people that possess one or no copies of this gene have 69% to 97% greater risk of acquiring HIV.

Another study found that protection against HIV may come from specific combinations of alleles that humans carry. Rare immune system alleles tend to provide greater protection against HIV. This is proven as HIV patients that have much lower viral loads than other patients carry particular rare gene variants (viral load refers to the number of viral particles in blood plasma and this is a way of measuring progression of HIV). This means that HIV has adapted to attack the dominant alleles in the population, which is the more common immune system alleles system. Research also proves that these people who confer the greatest protection have the least common gene variants in the population. An example given is based on African-American patients who were underrepresented in the study. They possessed less common immune system alleles and they are the ones who gave measured lower viral loads in their body

In response to the many possible factors regarding HIV attack and the possible reactions towards AIDS medication, there should be a better prediction of each individual patient’s risk of developing drug resistance, toxicity and long-term efficacy of therapy. One best way to be able to predict accurately is a simple genetic blood test and screening and this will help physicians to decide when to start therapy in an HIV-positive person, and what drugs to start treatment with so that proper treatment is achieved in each individual patient.

Links :

http://en.wikipedia.org/wiki/AIDS

http://www.infectiousdiseasenews.com/200511/genetics.asp

http://www.emaxhealth.com/53/2006.html

Cancer killer found in the ocean

Bradley Moore, Ph.D. Marine biochemist at Scripps Institution of Oceanography in San Diego has discovered that Salinispora tropica; a bacteria could be a new nature antibiotic. It can produce anti-cancer agents. Salinispora tropica was first found in the ocean sediments of Bahamas in 1991. Recently its genome was sequenced. The compound of ‘salinosporamide A’ was found in the bacteria which can be use to treat a bone marrow cancer, multiple myeloma, and some solid tumors.

The technique of sequencing mapping, ‘shotgun ‘, was approached by Moore and the Joint Genome Institute (JGI) of solving Salinispora tropica’s genome structure. The genes of Salinispora tropica were cut into small pieces and rebuilt. However, the experiment failed to solve the bacteria’s genome puzzle. “Instead, information about the natural chemistry of the organism helped close the sequencing gap”

Recently the researchers have succussed sequencing the genomes; the molecular basis of nature synthesis can be studied. The protein or enzyme can be predicted by the DNA sequence. Moore and his colleagues now are able to manipulate the enzymes and make new chemistry from it. ‘Salinosporamide A’ was the compound derived in the bacterium.

"By sequencing Salinispora tropica we are now able to look in greater detail at this organism and potentially pull out some of the other compounds from the gene clusters that may make highly potent anticancer agents," said Moore. The natural product that was created by the marine organism is currently being tested to treat cancer in humans, especially patients who suffer from a bone marrow cancer. They are hoping it could soon be tested to treat other cancers.

Futher reading:

http://www.sciencedaily.com/releases/2007/06/070613174715.htm

http://www.sciencedaily.com/videos/2007/1107-cancer_killer_found_in_the_ocean.htm

Post by Tzu-Ling Sung 41612040