Wednesday, April 28, 2010

DNA and Neurological Disease

Neurological diseases are devastating for sufferers and can be some of the most difficult diseases to treat. They may impact a person's daily life, including their mobility. They can also progressively worsen, which is painful for friends and family members when they watch a loved one deteriorate each day. Research into the mechanism of DNA as a basis for neurological diseases, however, has suggested promise for improving our understanding of the diseases and hopefully developing successful treatments one day.

What are Neurological Diseases?

Neurological diseases are disorders that involve the spinal cord, brain and also nerves in your body. These three parts exert a great deal of control over how your body works, which includes speech, movement, swallowing, breathing or thinking. A person's ability to recall information and their moods can also be affected. Examples of neurological diseases include:
  • Alzheimer's disease
  • Bell's Palsy
  • Huntington's disease
  • Epilepsy
  • Parkinson's disease
  • Cerebrovascular disease

DNA and its Relationship to Neurological Diseases

Research over the last several years has found that long sequences of abnormal DNA can cause extremely debilitating and rare neurological diseases. Researchers are trying to understand how these abnormalities actually occur in the DNA. In one study, the focus was on a neurological disorder called Friedreich's ataxia, which is damaging to the nervous system and gradually worsens over time. Those with the disease suffer from weakened muscles and difficulties speaking as well as heart disease.

If you recall that DNA reads bases in sets of three, you may more easily understand that in Friedreich's ataxia, a DNA triplet repeats itself - a guanine and two adenine bases, which are denoted by the first letter of each base, resulting in GAA. Since DNA base pairing is very specific, the complementary strand is two thymines and one cytosine, denoted by TTC. It was initially found that forty repeats of the triplet could occur without symptoms showing but we know that if more than forty repeats occur, many problems begin to take root. Also concerning is that the DNA itself is inherited, which is not particularly worrying if the pattern is less than forty repeats but it does become a problem when it occurs in greater numbers. The reason for this phenomenon is that the increasing number of repeats makes the sequence unstable. It also means that the sequence increases in each new generation. Unfortunately, the longer sequence causes more devastating effects from the disease.

DNA and Disease Prediction

DNA has become an extremely useful tool for predicting disease. By allowing medical professionals to identify genes in DNA that are markers for disease, a person can make appropriate lifestyle or similar modifications to help lower the risk of disease. For those diseases that are inherited, identifying a parent who is a carrier but does not express the disease can also help parents make informed choices regarding a potential pregnancy.

Predicting Heart Disease

The incidence of heart disease continues to rise in the United Kingdom (UK) and many other parts of the world. Heart disease is a complex interplay of lifestyle factors and genetics. Recently, researchers in the UK found a method for identifying those individuals who have an elevated risk of heart disease. They found that telomeres - miniscule DNA strands that are found at the ends of chromosomes - could provide valuable information about a person's chances of having heart disease. It was found that shorter telomeres suggested a greater risk of developing heart disease in men aged forty-five to sixty-four years old.

The telomeres were measured in leukocytes, also known as white blood cells. Researchers believe that as telomere length decreases, a person's chromosomes are more likely to mutate. This relates to the protective effect of telomeres, which help to prevent damage to chromosome ends. The research can hopefully allow medical professionals to eventually predict someone's risk of heart disease, which will mean allowing us to find new ways to prevent heart attacks.

Predicting Brain Disorders

Brain disorders such as Parkinson's disease and amyotrophic lateral sclerosis (ALS) are progressive disorders that lead to destruction of brain cells and functioning. In ALS, muscle use and mobility are lost, leading to death. Parkinson's disease results in tremors and compromised movement. Like ALS, no cure exists for Parkinson's disease, which means that research is vital to help scientists find effective treatments or a cure. New research has, however, provided clues about predicting these diseases.

In a research study based in the United States, scientists looked at data from people with ALS and Parkinson's disease as well as those who did not have the diseases. They found differences in genes that allowed them to predict those individuals who had an increased risk for the diseases.

These differences were noted after researchers investigated the axon guidance pathway. This pathway involves a complicated group of chemically mediated messages that are important in the brain during foetal growth. They work to support and repair the 'wiring' of the brain during a person's entire life. There were numerous differences in the pathway genes that relate to these diseases. In addition, researchers also found pathway genes that identify people at a very high risk of ALS, several thousand times that of the general population.

For Parkinson's disease, they discovered pathway genes that suggested a very high risk of approximately four hundred times that of the general population. It is hoped that for individuals who have a higher risk of the diseases, scientists will be able to create drugs that can target these pathways.

Friday, April 9, 2010

Bioinformatics and DNA

Understanding Bioinformatics
Bioinformatics involves applying computer technology to the handling and sorting of biological information. As such, we can use computers to analyse and make sense of this biological information. In a sense, bioinformatics is a bridge between the biological sciences and computer sciences. With so much information, bioinformatics can let us detect valuable data contained within enormous volumes of biological information. Once uncovered, this information can be applied to technological applications in fields such as medicine, agriculture, environmental sciences and nutrition.

Importance of Bioinformatics
Bioinformatics is important to a virtually unlimited number of fields. However, one of its biggest challenges is to obtain clarity within the massive amount of information that results from projects involving the sequencing of the human genome. Initially, this type of sequencing was performed solely in the laboratory but with such an enormous level of data production, we now rely on computers to accomplish sequencing goals.

To actually generate a DNA sequence and then store and analyse it, computers are responsible for much of the work. However, it is a challenge in bioinformatics to efficiently and successfully store such a large volume of data and to do so in such a way that a scientist can easily access the necessary information as needed. Data in itself is almost useless until it is analysed and correctly interpreted. To handle so much data, computers are important to fill this vital gap, which can aid scientists in the extraction of useful and important biological data.

Using Bioinformatics
Bioinformatics is used in many aspects of medicine and will likely continue to grow as we find new capabilities and applications. It has the potential to create custom medications, prevent or treat disease, benefit the environment or support agricultural technology.

In molecular medicine, we can obtain a higher number of drug targets through the use of bioinformatics. Another important area is that of gene therapy, which is a particularly strong focus of research at present. In agriculture, bioinformatics can allow us to enhance the nutrient quality of foods and develop crops that are able to handle poor soil growing conditions and bad weather. We can also develop our understanding of evolution through bioinformatics as well as broaden our understanding of environmental issues such as climate change. Clearly, bioinformatics is a significant area of science and it will continue to develop and support our research and understanding of DNA and the biology of organisms.

DNA Vaccines

Why Use DNA Vaccines?
There are numerous advantages of DNA vaccines over other vaccination methods. DNA vaccines are thought to trigger a broader range of immune responses, which means they would have more applications than traditional vaccines. Since traditional vaccines only cover certain diseases, the use of DNA vaccines to target a larger number of diseases could impact virtually everyone, given how easy it is to come into contact with one of the many diseases that exist.

Comparison of DNA Vaccines and Other Vaccines
To understand DNA vaccines it helps to have a sense of the differences between DNA vaccines and other vaccines used to protect from disease. First generation vaccines are those involving the entire organism, which may be live, 'damaged' or dead. Those vaccines that are live and attenuated trigger an antibody immune response as well as those entailing killer and helper T-cells. Still, there is a low chance that attenuated vaccines can still change to the toxic form, which means that in people with already weakened immune systems the vaccine could cause disease. Although vaccines that are killed do not have the same risk, they are not as effective in addressing a wide range of diseases.

Second generation vaccines were developed to address some of the concerns held regarding first generation vaccines. Second generation vaccines are subunit ones that are made up of mostly protein parts such as protein antigens or recombinant proteins although they do not trigger a killer T-cell response.

DNA vaccines constitute a third generation vaccine. These are comprised of a round, relatively small bit of bacterial DNA that has been modified to release one or more particular proteins - also known as antigens - from a microbe. After injection of the DNA vaccine, the recipient's cells translate the DNA into toxic proteins that are viewed as foreign invaders, which serves to begin an immune response.

Benefits of DNA Vaccines
DNA vaccines have many benefits in comparison with the more traditional types of vaccines. For instance, DNA vaccines are thought to provide a better immune response in patients with HIV. Patients with HIV suffer from poor immunity and increased susceptibility to disease. Since DNA vaccines afford the potential for treating chronic viral infections, they could be particularly beneficial for individuals with diseases such as HIV. DNA vaccines are considered cheaper to produce than traditional vaccines and thus provide an affordable way to provide large-scale vaccinations. Since DNA vaccines are also more stable with regards to temperature, they are easier to store and transport.

Limitations of DNA Vaccines
Thus far, the limitations of DNA vaccines mostly involve a lack of research, which will likely be remedied in the future when they become a more important area of interest. At present, there is a limitation in regards to microbial activity. While DNA is successful for providing an immune response when the target involves disease-causing proteins, there are some microbes that have an outer shell made of polysaccharides. Unfortunately, DNA vaccines are unsuccessful and instead, subunit vaccines that have a polysaccharide foundation are required.

Vaccines remain one of the most important developments of the twentieth century and they are responsible for saving millions of lives and even eliminating disease in some areas. Vaccines allow us to keep disease in controlled numbers and prevent the complications that arise when someone is afflicted with a disease.

DNA Mutations

How do DNA Mutations Occur?
Virtually every single person will have some sort of change to their DNA during their life. Changes can result from a multitude of mistakes, such as an error when DNA is replicated or through damage to DNA occurring from environmental or lifestyle factors. These include smoking, radiation and many others. Fortunately, your cells have special ways to handle these mistakes before they can cause damage. For some people, however, their body's repair systems can become overwhelmed if repeatedly exposed to a specific stimulus. For all of us as well, our DNA repair systems just do not operate nearly as successfully as we age. The end result for both of these scenarios is that changes in DNA will occur.

A DNA mutation can also be inherited. A germline mutation is one that can result in a disease that is clustered within one family. Some mutations can be quite specific, such as those that occur following excessive exposure to sunlight, which can cause changes in skin cells. Still other mutations may occur in the area of DNA related to sperm and egg production, which is also considered a germline mutation and is inheritable. If your child were to inherit a germline mutation from you, each cell in your child's body would carry this faulty DNA.

Differnet Types of Mutations
To understand the different types of mutations that can occur, it is important to know how a gene is constructed. Your DNA is full of genes, which are similar to words that make up a sentence. The four bases are known as adenine (A), thymine (T), guanine (G), and cytosine (C), each denoted by their first letter. Different sequences of these bases code for different proteins. If the sequence is modified, the entire meaning of the gene then changes and the instructions for producing the protein changes as well.

Point mutations are those that involve a basic change in a single base for the sequence. If we removed just a single letter from in a word or sentence, this would be akin to a point mutation. In contrast, a frameshift mutation involves the addition or removal of nucleotides. At the same time, if you think about the fact that DNA reads in sequences of three bases or 'letters,' the addition or removal of one or more letters alters every word that follows as the letters are all shifted. Therefore, the entire meaning of the sentence is changed.

Another type of mutation is a deletion mutation. Any mutation where DNA is ultimately missing a piece is called a deletion mutation. The mutation may be quite small and could involve deletion of only a single base or it could be larger and will impact numerous genes. A deletion mutation can even result in a frameshift mutation, where an entire 'word' is deleted. Conversely, a mutation that involves an additional piece of DNA is called an insertion mutation. In fact, these types of mutations can also result in frameshift mutations. Regardless of whether it is a deletion or insertion, a frameshift mutation usually translates into a protein that does not function properly.

Other mutations include inversion and expression mutations. In the latter, a whole section of a person's DNA is actually reversed while in an expression mutation, it is not just the protein that may be changed but the location where it is made or the amount of the protein produced. So basically, if you had this mutation, your body could be making a protein in a skin cell, for example, when it should be making it in a nerve cell.

There are obviously many different types of mutations but keep in mind that even if DNA repair is unsuccessful, the end result is not necessarily anything major or noticeably detrimental to your health. While the functions of DNA are important, many mutations happen that fortunately do not have dire consequences such as disease.

DNA Viruses

Most people encounter viruses at some point throughout their lifetime, which can leave them feeling miserable. We probably don't give a lot of thought to the molecular aspects of viruses and instead, just focus on getting rid of the painful symptoms when a virus strikes and compromises our health. If you stop for a minute and think about it, however, a lot is happening in our bodies when a virus invades. All of the symptoms you feel result from the collective effects of a virus as it inflicts your body's cells.

How Do Viruses Work?
A virus essentially inserts its own genetic material into a host cell and causes changes in the function of the host cell through the virus' genes. The host cell may lose many different abilities, such as control over its growth, its ability to divide and it may also show chromosomal abnormalities.

Like humans, viruses are composed of genetic material. In the case of a DNA virus, this genetic material is DNA. A DNA virus uses a copying mechanism, which relies on an enzyme called DNA polymerase - an important enzyme in DNA replication. DNA viruses are grouped according to the Baltimore classification system and there are more than twenty virus families and nearly a hundred genera. The viruses themselves include an enormous range, from more basic ones to highly complex viruses.

Different Kinds of DNA Viruses
There are numerous different groups of DNA viruses, with varying structures and effects. One group is herpes viruses, which are somewhat complex and have over one hundred genes. One of the herpes family of viruses is the Epstein Barr virus, which has been associated with a rare form of cancer. Epstein Barr virus is also the virus responsible for glandular fever - formally known as infectious mononucleosis, which is commonly seen in adolescents and college-aged adults. Pox viruses have several hundred genes and are effective at replicating once in a host. Papilloma viruses are those that cause warts and they are also associated with cancer. You have also likely heard of the Hepatitis B virus, which is actually a DNA tumour virus. There are many more DNA viruses but they all share a common link, which is that their genetic material is comprised of DNA.

Creating a DNA Virus
In some interesting research, scientists in the United States actually created a DNA virus with a new method that appears to be promising. The development of the virus could potentially lead to technologies for the production of cleaner forms of energy or even novel ways to buffer the effects of pollution. To create the virus, researchers put together and selectively cut segments of DNA. The process itself took approximately two weeks, which is not particularly long given the potential of the development. One exciting aspect of the research is that scientists believe that their ability to rapidly make longer pieces of DNA can allow them to improve understanding of specific genes. Their understanding could then be a turning point for the ability to eventually modify more complicated organisms.

While DNA viruses have many different effects in the body, our knowledge of their structure and mechanisms of infection can help us to learn more about treating diseases caused by DNA viruses. Better still, research has suggested that the creation of synthetic viruses can provide possibilities for addressing concerns such as pollution and the quest for better forms of energy provision.