GENETIC DISORDERS Earths inhabitants have populated all of the regions of the world, discovered places never dreamed

of, and have advanced beyond normal understanding, while man can still be conquered by an object which is immeasurably small. While man has been so busy trying to find a way to get rid of all pain and suffering, he has finally discovered that there are things that cannot be stopped. This relentless phenomenon is called a genetic disorder. A genetic disorder by definition is a medical condition caused by an error in a persons genetic material . Genetic disorders play an important role in life and must be learned about if humans are going to survive. Genetic disorders are disorders caused by a mutation in genes. Some genetic orders are caused by errors during meiosis. Examples include Downs Syndrome and Turner Syndrome. Inheriting defective genes from the parents can also cause genetic disorders. An example of an inherited genetic disease is Huntingtons disease. Genetic disorders are also divided into Single gene disorders and polygenic disorders. Single gene disorders are caused by one gene being mutated. Polygenic disorders are believed to be associated with many genes along with daily habits and environmental factors. Polygenic disorders are disorders that may be caused by the effects of genes inherited from mom and dad along with lifestyle choices and environmental factors. Disorders that are polygenic include heart disease, hypertension, diabetes and obesity. These diseases often run in the family but often dont follow conventional inheritance patterns. Single gene disorders can be inherited in several different ways. Certain disorders need only one mutated gene to show the phenotype in the offspring. Some genetic disorders are X-linked disorders. This means they are caused by mutations of the X chromosome. These disorders can be X-linked dominant or X-linked recessive. Examples of X-linked disorders are, Aicardi Syndrome, Muscular dystrophy and Androgenetic alopecia. There are also disorders that are Y-linked. These are disorders that only males can get because these are disorders linked to the Y chromosome. Male infertility can be caused by a mutation of the Y chromosome. This is autosomal dominant; examples of autosomal dominant disorders are Huntington's disease, and Marfan syndrome. Other disorders need two sets of the mutated gene to show the phenotype in the offspring. This is called autosomal recessive; Cystic fibrosis and Sickle Cell

Anemia are examples of an autosomal recessive disease. Being born with extra genetic information causes Down syndrome (DS). This disorder causes delays in child development and usually causes mental retardation. No one knows why DS occurs but it is known that women over 35 are more likely to have a child born with the condition.

To fully comprehend genetic disorders, one must understand the basics of genetics and its diseases. Some genetic disorders can already be seen at birth, while others dont show up until in childhood or adult life. In these instances it is usually harder for them to be identified. These disorders arent always serious though, they may cause such a small disease as color blindness or go all the way up to death. There have already been 9000 genetic disorders found and researched by scientists. What makes genetic disorders really stand out is their complexity. Genetic disorders are known for affecting at least more than 3 different parts of the body, thus making them harder to cure and more of a threat.

All genetic disorders involve genes of the nuclei in some way or fashion. Genes are made of DNA, Deoxy Ribo-Nucleic Acid, and are arranged specifically on chromosomes. Chromosomes are tight coils of chromatin, which is made up of DNA. Chromosomes are an instrumental factor in genetic disorders. Chromosomes are made up of a p arm and a q arm. P stands for petite or short, while q is the next letter in the alphabet, it means long. Located in the center of the chromosome is something called a centromere, pinched portion of the chromosome that connects both arms of the chromosome. Normal humans have 46 chromosomes, which means that they have 23 pairs of chromosomes. 44 of these chromosomes are normal, while that last two determine the gender of the individual. To understand chromosomes, a technique was made that could stain chromosomes so that they could be seen. After this innovation was discovered, a new technique rose called banding. There are many variations to chromosome banding. Examples of such variations are Q banding, G banding, and C banding. Each different form uses a separate medium to show the bands of the chromosome. The bands of chromosomes act as fingerprints, and allow humans to organized and recognize

them. A visual organized representation of chromosomes is called a karyotype. There are many different variations of karyotypes which go accordingly with the different chromosomes and genetic codes. A spectral karyotype distinguishes between chromosomes by color, while a classic one separates by pairing off in chronological order.

There are four main areas of genetic disorders, Chromosomal, Singlegene disorder, multifactorial, and Mitochondrial. Chromosomal disorders affect approximately seven out of every 1,000 infants. A chromosomal disorder is brought about when a person has too many or too few chromosomes, or when there is a change in the structure of a chromosome. Euploidy is the condition of having a normal number of structurally normal chromosomes. A euploid of any sort has the correct form of product. Aneuploidy is the condition of having less than or more that the normal diploid number of chromosomes. This condition is associated justly with cell genetic abnormalities. There are two common forms of aneuploidy, Monosomy and Trisomy. A monomy is the lack of a pair of chromosomes. An example of a disease caused by a monomy is Turners Syndrome. Turners syndrome is a monomy of the x chromosome. Instead of having two x chromosomes there is only one functioning chromosome. A Trisomy is having three chromosomes of a specific type. A common trisomy is trisomy 21. Trisomy 21 is Downs Syndrome. The 21st pair of chromosomes has three instead of just two. There is another type of aneuploidy called triploidy. A triploid has three of each chromosome. Most, if not all, individuals that are born as triploid are either dead already, or will die very soon. A chromosome deletion is when part of a chromosome has been either deleted or broken off and lost. A deletion may get rid of an entire chromosome, part of one, or a band. An example of a disease caused by a chromosome deletion is cri-du-chat. A chromosome duplication is when a section of a chromosome is duplicated. This is also called a partial trisomy. A new form of chromosome deformation has been discovered. It is called a chromosome ring. This is when one end of the chromosome may stick to the other and form a circle which will cause problems when cell division takes place. Another way this could happen is a form of cell fusion. A chromosomal translocation is when a portion of a chromosome switches with another portion and thus making a mixture of two different chromosomes. There are two different types of translocation, balanced and unbalanced. An

unbalanced translocation is more dangerous because there is probably three pieces of one chromosome, and only one of another. On the other hand, a balanced translocation shouldnt have that much trouble, because all of the genetic material is there, however if the individual seeks to have children, then there are certain risks involved. A chromosome inversion is when there are two breaks in one chromosome, then the two pieces are switched around, and put back into the chromosome. There are two different types of inversions. One is pericentric inversion, which means if the inverted area includes the centromere. If the inverted area does not include the centromere, then it is called a paracentric version. Chromosomal disorders are an important part of genetic disorders.

Single Gene disorders, inborn errors of metabolism or Mendelian disorders, are caused by non-working genes. Every gene has information used by cells used to manufacture a specific protein, or a component of a protein. A mistake in the DNA may cause a persons cells to fail to produce the correct number of a certain protein, or to make the protein wrong. These kinds of proteins will most likely not work correctly. In some instances, a faulty gene may have a dominant effect, in which the person has one faulty gene and one good one, and will have a disorder show up. If it has a recessive effect, then nothing will happen unless the individual gets two of those genes. Have of all single gene disorders are autosomal dominant. That means that the messed up gene is carried on an autosomal chromosome, a normal chromosome numbered one to forty four and excluding the sex chromosomes. People with this disorder have a fifty percent chance of continuing their disease onto their children. An example of this disorder would be Huntingtons Disease, which doesnt show up until an individual is thirty or forty. There are also autosomal recessive disorders. This happens when a person has two faulty copies of the gene. These parents would have a 25 percent chance of passing it on to their children if they were both carriers of this disorder. An example of this disorder is cystic fibrosis. This disorder affects many different regions of the body. Some single gene disorders are not entirely dominant or recessive and are just called co-dominant. An example of this disorder is Sickle Cell Anemia. This is when the red blood cells are misshapen and dont carry enough oxygen and dont move as fast through the vessels.

There is a single gene disorder which is x-linked. These stem from a gene located only on the x chromosome. Males have a better chance of receiving these disorders than women. An example of this disease is Hemophilia, where the body cant clot blood or produce platelets.

Multifactorial disorders are caused by gene variations as well as a persons environment. An example of a multifactorial disorder is neural tube. This is when the structure that develops the spinal chord and brain is damaged. Some diseases that run in families, but arent obviously inherited are thought to be multifactorial disorders. An example of one of these diseases is coronary heart disease. In these cases a person is predisposed to get the disease, but a change in lifestyle could affect it and stop it from happening.

Mitochondrial disorders result from problems with the mitochondrias DNA inside the cell. Sperm and eggs have mitochondria, but a sperm only gives its nucleus to the egg, so mitochondrial disorders are passed solely by the mother. Both males and females may be affected, but an affected male will not pass it on to his children. Conditions involving mitochondrial inheritance are rare, though one example is called Lebers hereditary optic neuropathy. This is a vision disorder that shrinks the optic nerve.

There are many different ways to tell if someone may have a genetic disorder, these techniques are called genetic screening. A test that can be done at the earliest part of life is called the pre-implantation diagnosis, which works with in vitro fertilization, joining a sperm and egg outside of a womans body. Physicians can remove a cell from the embryo to test for a disorder. Prenatal screening, screening done during pregnancy, is used to identify fetuses that run a risk of getting a genetic disorder. This is done by testing the womans blood for specific substances known to be involved in genetic disorders. Genetic screening of newborn children is necessary to see if the child may have a disorder that must be dealt with immediately. If diagnosed early enough, an infant may be treated and have a chance of being cured. Carrier screening is done to see if a couple are carriers of a disorder before they have children. There are many different races that run different risks of different disorders.

Some receive the disorder more readily. A family history screening helps identify healthy individuals who may have a risk of getting a disorder, or passing it along to their children. A doctor takes information from as far as three generations back to produce a pedigree. The pedigree is able to help identify the risks of genetic disorders. There is a new form of detection tool in genetics right now, it is called FISH. This stands for fluorescent in situ hybridisation. These methods work well and are becoming more popular in detecting disorders.

One lethal disorder inherited as a recessive allele is Tay-Sachs disease. This is caused by a dysfunctional enzyme that fails to break down brain lipids of a certain class. The symptoms usually become manifest a few months after birth. Some symptoms are seizures, blindness and degeneration of motor and mental performance. Death is the result of this disease, in children. With Tay-Sachs disease, the brain cells of a baby are unable to metabolize gangliosides, a type of lipid, because a crucial enzyme does not work properly. As the lipids accumulate in the brain, the brain cells gradually cease to function normally. Only children who inherit two copies of the Tay-Sachs allele qualifies as a recessive. At the biochemical level, we observe an intermediate phenotype characteristic of incomplete dominance: The enzyme deficiency that causes Tay Sachs disease can be detected in heterozygotes, who have an activity level of the lipid-metabolizing enzyme that is intermediate between individuals homozygous for the normal allele and individuals with Tay-Sachs disease. Heterozygotes lack symptoms of the disease, apparently because half the normal amount of functional enzyme is sufficient to prevent lipid accumulation in the brain. In fact, heterozygous individuals produce equal numbers of normal and dysfunctional enzyme molecules. At the molecular level, the normal allele and the Tay-Sachs allele are codominant. Sickle-cell disease is caused by the substitution of a single amino acid in the hemoglobin protein of red blood cells. When the oxygen content of an affected individuals blood is low, the sickle-cell hemoglobin deforms the red cells to a sickle shape. Sickling of the cells, in turn, can lead to other symptoms. The multiple effects of a double dose of the sickle-cell allele exemplify pleiotropy, which is the ability of a gene to affect an organism in many ways. Regular

blood transfusions could be used to ward off brain damage in children with sickle-cell disease. Heterozygotes with the sickle-cell allele may suffer some symptoms of the disease when there is a reduction of blood oxygen. Since the two alleles are codominant at the molecular level; both normal and abnormal hemoglobins are made. Only individuals who are homozygous for the sicklecell allele suffer from the disease. Down syndrome is an aneuploid condition, meaning that if either of the aberrant gametes unites with a normal one at fertilization, the offspring will have an abnormal chromosome number. Down syndrome is usually the result of an extra chromosome, so that each body cell has a total of 47 chromosomes. In chromosomal terms, the cells are trisomic for chromosome 21. Its trisomy severely alters the individuals phenotype. Down syndrome includes characteristic facial features, short stature, heart defects, susceptibility to respiratory infection, and mental retardation. Most cases of Down syndrome result from nondisjunction during gamete production in one of the parents. Nondisjunction, being something in which the members of a pair of homologous chromosomes do not move apart properly during meiosis I, or in which sister chromatids fail to separate during meiosis II. In these cases, one gamete receives two of the same type of chromosome and another gamete receives no copy. There is a correlation of Down syndrome with maternal age, the hypothesis that older women are more likely than younger women to carry Down babies to term rather than spontaneously aborting the trisomic embryos. One way to detect this is to use an amniocentesis, which can determine whether a developing fetus has these diseases. Tests for disorders are performed on cells grown in the laboratory from the fetal cells that had been sloughed off into the amniotic fluid. In an alternative technique called chorionic villus sampling, the physician suctions off a small amount of fetal tissue from the placenta. These results can be found quicker, within 24 hours.

[Children] with Down syndrome tend to share certain physical features such as a flat facial profile, an upward slant to the eyes, small ears, a single crease across the center of the palms, and an enlarged tongue. A doctor can usually tell if a newborn has the condition through a physical exam (Kids Health). Children with Down syndrome, often do everything later than a normal baby

i.e. sit up by themselves, crawl and walk. Most children with DS suffer from mild to moderate mental retardation. The child will still learn but often at a slower pace than a normal child. Some children with DS have serious health issues while others have few to no health issues. Many DS children have heart problems and high blood pressure. Often children with DS also have vision and hearing problems. Other medical conditions that may occur more frequently in children with DS include thyroid problems, intestinal abnormalities, seizure disorders, respiratory problems, obesity, an increased susceptibility to infection, and a higher risk of childhood leukemia (Kids Health). Huntingtons disease is passed on as an autosomal dominant trait from parents to offspring. Huntington's disease is a genetic, progressive, neurodegenerative disorder characterized by the gradual development of involuntary muscle movements affecting the hands, feet, face, and trunk and progressive deterioration of cognitive processes and memory (dementia) (WebMD). Currently there are a number of medications available to help control the symptoms of Huntingtons, however there is not currently a way to stop or reverse the effects of Huntingtons. Muscular dystrophy (MD) is a genetic disorder and is an X-linked disorder. The muscular dystrophies (MD) are a group of more than 30 genetic diseases characterized by progressive weakness and degeneration of the skeletal muscles that control movement. MD has many forms that act differently and can be seen in humans of many ages from infant to adult. Duchenne MD is the most common form of MD and primarily affects boys. It is caused by the absence of dystrophin, a protein involved in maintaining the integrity of muscle. Onset is between 3 and 5 years and the disorder progresses rapidly. Facioscapulohumeral MD usually begins in the teenage years. It causes progressive weakness in muscles of the face, arms, legs, and around the shoulders and chest. It progresses slowly and can vary in symptoms from mild to disabling. Myotonic MD is the disorder's most common adult form and is typified by prolonged muscle spasms, cataracts, cardiac abnormalities, and endocrine disturbances. Individuals with myotonic MD have long, thin faces, drooping eyelids, and a swan-like neck. (NINDS). As with Huntingtons disease, there is currently no way to stop or reverse any form of MD. In some cases, Autism has been shown to be genetically passed to offspring.

Autism is an example of a polyphonic disorder; this means that several genes are affected when an offspring exhibits this disorder. Autism has a strong genetic basis, although the genetics of autism are complex and it is unclear whether ASD is explained more by multigene interactions or by rare mutations with major effects (Autism). Autism is a brain development disorder. Parents can begin to see signs of Autism early on in a childs life. Autistic infants often smile less often and do not respond to social stimuli as much as a normal child would. Autistic toddlers often do not spontaneously socialize with other children. It is not that they prefer to be alone but rather relationships are hard for them to develop. Autistic children often do not begin to talk at the normal time for children. They will try to communicate in screams and other noises that seem to mean nothing to the parents but are actually their way of trying to communicate. Young Autistic children will also exhibit actions similar to Obsessive Compulsive Disorder (OCD). They will obsessively stack toys or line them up perfectly. They will then become angry if the stack or line becomes disordered. Autistic children often resist change. They also like routine, such as an unvarying menu or a dressing routine. While Autism is not curable, parents can consult a doctor for ways to manage it. Children with autism generally benefit most from a highly structured environment and the use of routines. Treatment for autism may include a combination of the following: Special education: Education is structured to meet the child's unique educational needs, Behavior modification: This includes strategies for supporting positive behavior, Speech, physical, or occupational therapy: These therapies are designed to increase the child's functional abilities (WebMD). Sickle Cell Anemia is an autosomal recessive disease. This means that the child has to receive two recessive genes, one from each parent. Children are born with sickle cell hemoglobin, which they inherit from their parents. Individuals may be carriers who have sickle cell trait or may actually have sickle cell disease. People who inherit only one sickle cell gene are carriers, but people who inherit two sickle cell genes have sickle cell disease (WebMD). Sickle Cell Anemia is a genetic disease that affects blood cells. Sickle cell [Anemia] is a genetic (passed from parent to child) disorder that affects the body's blood cells. In this disease, faulty hemoglobin (a substance that carries oxygen in the blood) causes the red blood cells to change shape

when oxygen is released to tissues (WebMD). Some of the symptoms of Sickle Cell Anemia are pain fatigue and swelling and inflammation of joints. People can be diagnosed in people at any age. Sickle cell disease is diagnosed by examining a sample of blood under a microscope. When the abnormal sickle-shaped cells in the blood are identified, a diagnosis is made. Also, a blood test called the hemoglobin electrophoresis can determine if a person has the disease or is a carrier (WebMD). Currently Sickle Cell Anemia is not curable. How ever there are many ways to keep the symptoms under control. Treatment of sickle cell disease depends upon the symptoms a person is experiencing. Some medications that can be used to treat sickle cell diseaserelated pain include: Opioid medications, Hydroxyurea (for example, Hydrea and Droxia), Anti-inflammatory medications such as aspirin and ibuprofen, Tricyclic antidepressants such as Elavil, Anticonvulsants such as Gabapentin (WebMD). Genetic disorders have many different shapes and forms. From autosomal dominate to autosomal recessive. There are also genetic disorders that are Ylinked and others that are X-linked. Other disorders are polyphonic or require several genes to be mutated. It is necessary the genetic disorders must continue to be studied if man is ever to have a chance against such a formidable enemy. Currently there are no permanent cures for genetic disorders. In order to find these cures, there still must be considerable leaps in the fields of genetic screening and genetic therapy. There is no way that people can just stumble upon something in such a complex subject as genetic disorders. Although people still die as a result of man not knowing enough, there is the fact that he never will. No matter how hard man tries, he can never fully understand something so complex and perfect as genetics.

TREATMENT OF GENETICAL DISORDERS

One day it may be possible to treat an unborn child for a genetic disease even before symptoms appear. This is a controversy because a lot of the techniques being developed have caused problems and also because there is a strong debate as to whether gene therapy should just be used for individuals or whether attempts should be made to eliminate genetic disease altogether. Each DNA molecule has along its length a sequence of the four types of bases, adenine, thymine, cytosine and guanine. Two DNA are joined to form a double helix. Complimentary base pairing ensures that adenine always pairs with thymine and cytosine with guanine. A gene is a section of DNA several thousand bases long. A gene codes for a part of a protein called a polypeptide and this code is carried in the sequence of bases along one of the DNA molecules. Three bases in sequence, a triplet, codes for an amino-acid, the building block of a protein. The unique sequence of bases codes for a unique polypeptide. The polypeptide forms part of a unique protein. Proteins have very specific roles and work with other molecules in the body for metabolism or structural reasons. The very beginning of any of these uses is the decoding of genes to make the proteins. DNA and therefore the genes are usually accurately copied every time a cell divides. However, mistakes and mutations can occur and this means that the base sequence and hence the code will be altered, This will mean that the gene will not code properly for the polypeptide, sometimes causing a genetic disease such as cystic fibrosis, sickle cell anaemia, and haemophilia. As more is learned about human genetics, it seems that diseases such as diabetes, cancer, heart disease, and some manic depressive illnesses also partly result from faulty DNA information. Genetic diseases can range from very mild to very serious and life threatening. The treatment can also range from none needed to none available. With some diseases such as colour blindness or dwarfism the affected person just adjusts and gets on with life. With other diseases such as cystic fibrosis daily treatment is needed to keep the child alive. Bubble baby syndrome can involve the child being kept in complete isolation, distressing for the child and the rest of the family. Some genetic diseases can be treated with drugs, blood transfusions, changes in diet, or even the transplantation of body organs. E.g. clotting factor can be administered to patients with haemophilia. But not all genetic diseases can be

treated this way. Gene therapy inserts normal genes with the correct genetic code into the cells containing the defective genes. Then the correct protein could be made so that the cells function properly and hopefully reduce or eliminate the symptoms of the disease. In the case of haemophilia the cells could then make their own clotting factor. Before a genetic disease can be treated the genetic defect must be accurately diagnosed. Short pieces of DNA called DNA probes can be designed to stick very specifically to certain other pieces of DNA because of complimentary pairing of the bases. DNA probes are very specific and more sensitive than normal ways of diagnosing. In the future defective and normal genes may be able to be told apart. The most common method of gene therapy is the insertion of a functioning or good gene to replace the non-functioning or bad gene. Scientists have developed methods for inserting genes into human somatic (non-reproductive) cells. The gene to be inserted is isolated and multiple copies made in the lab. The next stage is to insert these genes into cells and make them work properly inside the cells. This means that the gene must produce the correct polypeptide. One method for inserting genes into cells is to insert the good gene into a virus that has been made harmless so that it cannot infect cells. The cells are temporarily removed from a patient's body and the virus or vector used to carry the desired gene put into them. Then the treated cells, which now contain the correct genetic information, are returned to the patient's body. For example, bone marrow, liver cells, or white blood cells could be removed from the body of a patient, treated in the laboratory, and returned to the patient. There are other methods for gene delivery other than a virus. These are: Directly putting therapeutic DNA into target cells. This can be used only with certain tissues and requires large amounts of DNA. A lipid sphere called liposomes can carry the gene through the target cells membrane. Linking the DNA to a molecule that will bind to special cell receptors which means that the DNA can enter the cell more easily. Researchers also are experimenting with introducing a 47th (artificial human) chromosome into target cells. This would carry large amounts of code but there would be problems with delivering such a large molecule to the nucleus of a target cell. Cells in the human body can be divided into two sorts, somatic (nonreproductive) cells and germ line (reproductive) cells. Most cells in the body are

somatic. Somatic cells do everything except pass on information to the next generation. Germ cells include eggs in women and sperm in men. The genes in sperm and egg cells store information that will go to one's children. (paraphrased from http://www4.od.nih.gov/oba/rac/cover.htm ) Somatic gene therapy involves introducing a "good" gene into cells with bad genes. These introduced genes do not get passed along to the patients children. The genetic disease is treated but the disease may still be inherited by the patient's children. This is the more common form of gene therapy. The advantages of this is that if problems arise only one or a few individuals are affected and the new gene cannot be passed onto the next generation. However, the death of anyone is unacceptable in gene therapy. At the moment this form of gene therapy is still experimental and has not proven very successful in clinical trials. In 1999, gene therapy suffered a major setback with the death of 18-year-old Jesse Gelsinger who was part of a gene therapy trial for an enzyme deficiency (OTCD). He died from multiple organ failures four days after starting the treatment. His death is believed to have been caused by a severe immune response to the adenovirus carrier. (http://www.ornl.gov/sci/techresources/Human_Genome/medicine/genetherapy. shtml) Germline gene therapy involves modifying the genes in egg or sperm cells, which will then pass any genetic changes to future generations. This may involve inserting a new gene or trying to fix the damaged one. However, although this could prevent genetic disease being inherited, this form of gene therapy is very controversial. Very little research is being done in this area, both for technical and ethical reasons and this has not been trialled in humans yet. The techniques to change the genes are quite difficult and many cells can die in the process. Ethically it is hard to accept a lot of eggs and sperm dying as a result of experimentation. Also, if a mistake was made it would be impossible to eliminate and it would be passed on to subsequent generations. At the moment gene therapy is only done through clinical trials which take many years to carry out. No gene therapies are available for general use yet. This is because gene therapy does have risks and limitations. These are discussed in the following paragraphs. The gene therapy often doesnt last because the DNA is unstable or doesnt work for long. As the cells the gene is introduced into are often dividing very rapidly this can put wear and tear on the gene. This means that patients have

to have the therapy repeated which is costly both in money and time spent in hospitals. The immune system is designed to attack any foreign invader introduced into human tissues. This means that anything introduced, such as the gene or the vector carrying it, could be attacked. Also, seeing the immune system is designed to respond faster to the same invader the next time it is introduced, repeat therapy becomes very risky. This is another reason for not wanting to repeat the therapy. Viruses are the best way of inserting new genes. However, there are concerns about the toxicity of the virus, any immune responses, and getting the virus to the right place in the body. Also the virus, once inside the patient, may recover its ability to cause disease and infect the patient and other people. When a good gene is put into any cells it is impossible at the moment to control where the gene is inserted into the patients other genetic material. This may mean that another gene essential to the patient may be knocked out by the new gene. This will cause all sorts of problems depending on which gene is knocked out. Also, genes in the new place could produce too much or too little of the protein they are designed to make. If the protein is an enzyme this may mean that the finely balanced reactions in the body are affected. If the protein has a function such as part of a cell membrane then the cell memebrane will not work effectively. Diseases that arise from one gene being affected are the best to treat as only one new gene needs to be inserted. Unfortunately, some commonly occurring disorders such as heart disease, diabetes, and Alzheimer's disease are caused by many genes acting together. These are very hard to treat by gene therapy. There has been some initial success in treating a disease called severe combined immune deficiency (SCID), or Bubble Baby syndrome by treating somatic cells. A mutated gene stopped the production of an enzyme essential for the development of a normal immune system. Scientists isolated the normal copy of the gene and put it into a virus vector. The vector transported the gene into the patient's own bone marrow cells. Immune system cells are made by bone marrow cells. The treated bone marrow cells were then given back to the patient and normal, functioning immune cells made. The children dont need to remain in isolation any more. Fifteen children had been treated in this way until the trial had to be stopped. This is because two children subsequently contracted leukemia. This happened because you cannot put new genes exactly where you want them to go. In this case the new gene was inserted next to an oncogene (a

gene capable of causing cancer), causing leukaemia. (http://www.newscientist.com/article.ns?id=dn2878). This example highlights many of the problems and also the possible successes of gene therapy.. Recent developments in gene therapy: A virus has been inserted into the cells taken from people with congestive heart failure. The cells were then able to contract properly again. The gene blocks an enzyme which causes heart failure if too much is produced. Genes have been put into the brain using liposomes coated in a special polymer. The transfer of genes into the brain has been very hard because viral vectors are too big to get across the "blood-brain barrier." This method has potential for treating Parkinson's disease. Techniques could be used to switch off genes so diseases such a Huntingtons could be treated. Messenger RNA made from a defective gene could be mended rather than the actual DNA making up the gene. Techniques underdevelopment are: The abnormal gene could be repaired through a technique called selective reverse mutation, which makes the gene work properly. The regulation (how a gene is turned on or off) of a particular gene could be altered. Ethical considerations: There are many ethical considerations in discussing gene therapy. One of the important issues is the question of who decides what is normal and what is a disability or disease. A doctor or researcher may think that a genetic disease is more of a problem than the sufferer does. Jesse Gelsinger apparently was coping well with his genetic disease but thought that he could help to test new treatments. Unfortunately it cost him his life. This leads on to the question of whether disabilities need to be cured or prevented, rather than just being managed. Are they just part of being human? And does searching for a cure devalue the lives of individuals who have the diseases at the moment? Another important point is whether somatic gene therapy is more or less ethical than germline gene therapy (which is done in egg and sperm cells and prevents the trait from being passed on to further generations). In cases of somatic gene therapy, the procedure would have to be repeated in future generations for each individual that inherits the disease. However, if mistakes are made or the patient has a severe immune response, only that individual is affected. Although any death is unacceptable, any research needs to weigh up any risks inherent in the

disease versus the risks of the treatment. In the case of germline therapy the big advantage is that a particular genetic disease would be eliminated for good. The huge disadvantage is that the inserted gene could not be taken back if there where any mistakes or bad reactions. Other issues are the fact that gene therapy is very expensive to develop. Will this therapy be just be for the wealthy? If all are to have it will the taxpayer be happy to pay? Also, for gene therapy to work there would probably have to be extensive animal trials. These are becoming less and less popular with certain groups in the population. Conclusion: Treating genetic diseases with gene therapy does have its problems at the moment, both scientific and ethical. There were two key issues being discussed in this case study. One was the safety of gene therapy at the moment and the other was whether gene therapy should be just for somatic cells or whether the germline should be changed as well. With the experience of the death of Jesse Gelsinger and the Bubble baby children with leukemia it has been shown that there are real safety issues to be considered. However, it is very hard to tell how extensive these problems are as only a few humans have taken part in gene therapy trials. Unfortunately it is very hard to ethically justify continuing with human trials when there are real safety issues. Much of the pre-testing at the moment takes place in cell cultures These lines of research need to be developed more but they only give an indication of how the therapy works in these cells, not how a whole human body will react. An immune response cannot be mimicked in cell cultures. Research is both time consuming and expensive. After the laboratory work is done there needs to be clinical trials and these take many years. It is interesting that no gene therapies are available for general use yet. I also think it is much too risky to attempt to change the germline at this stage in the research. There are far too many safety issues to be sorted out to take the chance. This could only happen when any mistakes could be corrected immediately before they were inherited. If safety problems are fixed the genetic diseases most likely be treated would be the ones where the normal gene needs to be introduced only once into only one organ. Another example, other than the Bubble Baby Syndrome is phenylketonuria (PKU) which all new borns in New Zealand are tested for. PKU affects about one in 12,000 children of European ancestry, and if not treated early can result in severe mental retardation. If detected early, the child

can be placed on a special diet for their first few years but this can be very hard to stick to. Rare diseases such as Lesch-Nyhan syndrome, a distressing disease in which the patients are unable to manufacture a particular enzyme could also be cured. This leads to a distressing impulse for self-mutilation, including very severe biting of the lips and fingers. Although there are other means of treating genetic disease some are very distressing and aren't responsive to conventional therapies. Gene therapy may offer hope that wasnt there just a short time ago. This report mainly just discussed one technique, the insertion of good gene into a cell to correct a bad gene. But there are other techniques being developed and these may prove safer in the future. REFERENCE WIKIPEDIA MEDLINEPLUS NHBI