Genetic erosion is a process whereby an already limited gene pool of an endangered species of plant or animal diminishes even more when individuals from the surviving population die off without getting a chance to meet and breed with others in their endangered low population.Genetic erosion occurs because each individual organism has many unique genes which get lost when it dies without getting a chance to breed. Low genetic diversity in a population of wild animals and plants leads to a further diminishing gene pool, inbreeding and a weakening immune system and fast tracks that species towards eventual extinction.All the world's endangered species are plagued by varying degrees of genetic erosion and most need a human assisted breeding program to keep their population viable and to keep them from going extinct in the long run. The more critically endangered the species is (the smaller the population is), the more magnified the effect of genetic erosion gets when each surviving individual of the species is lost without getting a chance to breed.Genetic erosion gets compounded and accelerated by habitat fragmentation, today most endangered species live in smaller and smaller chunks of fragmented habitat interspersed with human settlements and farmland making it impossible for them to naturally meet and breed with others of their kind, many die off without getting a chance to breed and pass on their genes in the living population.The gene pool of a species or a population is the complete set of unique alleles that would be found by inspecting the genetic material of every living member of that species or population. A large gene pool indicates extensive genetic diversity, which is associated with robust populations that can survive bouts of intense selection. Meanwhile, low genetic diversity (see inbreeding and population bottlenecks) can cause reduced biological fitness and an increased chance of extinction.
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• Loss of function experiments, such as in a gene knockout experiment, in which an organism is engineered to lack the activity of one or more genes. This allows the experimenter to analyze the defects caused by this mutation, and can be considerably useful in unearthing the function of a gene. It is used especially frequently in developmental biology. A knockout experiment involves the creation and manipulation of a DNA construct in vitro, which, in a simple knockout, consists of a copy of the desired gene, which has been slightly altered such as to cripple its function. The construct is then taken up by embryonic stem cells, wherein the engineered copy of the gene replaces the organism's own gene. These stem cells are injected into blastocysts, which are implanted into surrogate mothers. Another method, useful in organisms such as Drosophila (fruitfly), is to induce mutations in a large population and then screen the progeny for the desired mutation. A similar process can be used in both plants and prokaryotes.
• Gain of function experiments, the logical counterpart of knockouts. These are sometimes performed in conjunction with knockout experiments to more finely establish the function of the desired gene. The process is much the same as that in knockout engineering, except that the construct is designed to increase the function of the gene, usually by providing extra copies of the gene or inducing synthesis of the protein more frequently.
• Tracking experiments, which seek to gain information about the localization and interaction of the desired protein. One way to do this is to replace the wild-type gene with a 'fusion' gene, which is a juxtaposition of the wild-type gene with a reporting element such as Green Fluorescent Protein (GFP) that will allow easy visualization of the products of the genetic modification. While this is a useful technique, the manipulation can destroy the function of the gene, creating secondary effects and possibly calling into question the results of the experiment. More sophisticated techniques are now in development that can track protein products without mitigating their function, such as the addition of small sequences that will serve as binding motifs to monoclonal antibodies.
• Expression studies aim to discover where and when specific proteins are produced. In these experiments, the DNA sequence before the DNA that codes for a protein, known as a gene's promoter, is reintroduced into an organism with the protein coding region replaced by a reporter gene such as GFP or an enzyme that catalyzes the production of a dye. Thus the time and place where a particular protein is produced can be observed. Expression studies can be taken a step further by altering the promoter to find which pieces are crucial for the proper expression of the gene and are actually bound by transcription factor proteins; this process is known as promoter bashing.
Genetics a discipline of biology, is the science of heredity and variation in living organisms. The fact that living things inherit traits from their parents has been used since prehistoric times to improve crop plants and animals through selective breeding. However, the modern science of genetics, which seeks to understand the process of inheritance, only began with the work of Gregor Mendel in the mid-nineteenth century. Although he did not know the physical basis for heredity, Mendel observed that organisms inherit traits via discrete units of inheritance, which are now called genes.Genes correspond to regions within DNA, a molecule composed of a chain of four different types of nucleotides—the sequence of these nucleotides is the genetic information organisms inherit. DNA naturally occurs in a double stranded form, with nucleotides on each strand complementary to each other. Each strand can act as a template for creating a new partner strand—this is the physical method for making copies of genes that can be inherited.The sequence of nucleotides in a gene is translated by cells to produce a chain of amino acids, creating proteins—the order of amino acids in a protein corresponds to the order of nucleotides in the gene. This relationship between nucleotide sequence and amino acid sequence is known as the genetic code. The amino acids in a protein determine how it folds into a three-dimensional shape; this structure is, in turn, responsible for the protein's function. Proteins carry out almost all the functions needed for cells to live. A change to the DNA in a gene can change a protein's amino acids, changing its shape and function: this can have a dramatic effect in the cell and on the organism as a whole.Although genetics plays a large role in the appearance and behavior of organisms, it is the combination of genetics with what an organism experiences that determines the ultimate outcome. For example, while genes play a role in determining an organism's size, the nutrition and other conditions it experiences after inception also have a large effect.
There are a number of ways through which genetic engineering is accomplished. Essentially, the process has five main steps
1.Isolation of the genes of interest
2.Insertion of the genes into a transfer vector
3.Transfer of the vector to the organism to be modified
4.Transformation of the cells of the organism
5.Selection of the genetically modified organism (GMO) from those that have not been successfully modified
Isolation is achieved by identifying the gene of interest that the scientist wishes to insert into the organism, usually using existing knowledge of the various functions of genes. DNA information can be obtained from cDNA or gDNA libraries, and amplified using PCR techniques. If necessary, i.e. for insertion of eukaryotic genomic DNA into prokaryotes, further modification may be carried out such as removal of introns or ligating prokaryotic promoters.
Insertion of a gene into a vector such as a plasmid can be done once the gene of interest is isolated. Other vectors can also be used, such as viral vectors, bacterial conjugation, liposomes, or even direct insertion using a gene gun. Restriction enzymes and ligases are of great use in this crucial step if it is being inserted into prokaryotic or viral vectors. Daniel Nathans and Hamilton Smith received the 1978 Nobel Prize in Physiology or Medicine for their isolation of restriction endonucleases.
Once the vector is obtained, it can be used to transform the target organism. Depending on the vector used, it can be complex or simple. For example, using raw DNA with gene guns is a fairly straightforward process but with low success rates, where the DNA is coated with molecules such as gold and fired directly into a cell. Other more complex methods, such as bacterial transformation or using viruses as vectors have higher success rates.
After transformation, the GMO can be selected from those that have failed to take up the vector in various ways. One method is screening with DNA probes that can stick to the gene of interest that was supposed to have been transplanted. Another is to package genes conferring resistance to certain chemicals such as antibiotics or herbicides into the vector. This chemical is then applied ensuring that only those cells that have taken up the vector will survive.
Lung cancer is a disease of uncontrolled cell growth in tissues of the lung. This growth may lead to metastasis, which is the invasion of adjacent tissue and infiltration beyond the lungs. The vast majority of primary lung cancers are carcinomas of the lung, derived from epithelial cells. Lung cancer, the most common cause of cancer-related death in men and the second most common in women is responsible for 1.3 million deaths worldwide annually. The most common symptoms are shortness of breath, coughing (including coughing up blood), and weight loss.
The main types of lung cancer are small cell lung carcinoma and non-small cell lung carcinoma. This distinction is important, because the treatment varies; non-small cell lung carcinoma (NSCLC) is sometimes treated with surgery, while small cell lung carcinoma (SCLC) usually responds better to chemotherapy and radiation. The most common cause of lung cancer is long-term exposure to tobacco smokeThe occurrence of lung cancer in nonsmokers, who account for as many as 15% of cases , is often attributed to a combination of genetic factors, radon gas, asbestos, and air pollution,including secondhand smoke.
Lung cancer may be seen on chest radiograph and computed tomography (CT scan). The diagnosis is confirmed with a biopsy. This is usually performed via bronchoscopy or CT-guided biopsy. Treatment and prognosis depend upon the histological type of cancer, the stage (degree of spread), and the patient's performance status. Possible treatments include surgery, chemotherapy, and radiotherapy. With treatment, the five-year survival rate is 14%.
Positron emission tomography (PET) scan For a PET scan, you receive an injection of glucose (a form of sugar) that contains a radioactive atom. The amount of radioactivity used is very low. Cancer cells in the body are growing quickly, so they absorb large amounts of the radioactive sugar. A special camera can then be used to create a picture of areas of radioactivity in the body. The picture is not finely detailed like a CT or MRI scan, but it can provide helpful information about your whole body. A PET scan can help give the doctor a better idea of whether a thickening of the pleura or peritoneum seen on another imaging test is more likely cancer or merely scar tissue. If you have been diagnosed with cancer, your doctor may use this test to see if the cancer has spread to lymph nodes or other parts of the body. A PET scan can also be useful if your doctor thinks the cancer may have spread but doesn't know where. Some newer machines are able to perform both a PET and CT scan at the same time (PET/CT scan). This allows the doctor to compare areas of higher radioactivity on the PET scan with the more detailed appearance of that area on the CT. Magnetic resonance imaging (MRI) scan Like CT scans, MRI scans provide detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. The energy from the radio waves is absorbed and then released in a pattern formed by the type of body tissue and by certain diseases. A computer translates the pattern into very detailed images of parts of the body. A contrast material called gadolinium is often injected into a vein before the scan to better see details. MRI scans can sometimes help determine the exact location and extent of a tumor since they provide detailed images of soft tissues. For mesotheliomas, they may be useful in looking at the diaphragm (the thin band of muscle below the lungs that is responsible for breathing), a possible site of cancer spread. MRI scans may be a little more uncomfortable than CT scans. They take longer -- often up to an hour. You may be placed inside a large cylindrical tube, which is confining and can upset people with a fear of enclosed spaces. Newer, more open MRI machines can help with this if needed. The MRI machine makes buzzing and clicking noises that you may find disturbing. Some places will provide earplugs to help block this out. Blood tests Blood levels of certain substances are often elevated in people with mesothelioma:
• osteopontin • soluble mesothelin-related peptides (SMRPs), detected with the MesoMark® test Blood tests for these substances are not used to diagnose the disease, but elevated levels may make the diagnosis more likely. Thus far, these blood tests have proven more useful in people who have already been diagnosed to follow their progress during and after treatment. If mesothelioma is diagnosed, other blood tests will be done to check the blood cell counts and levels of certain chemicals in the blood. These tests can give the doctor an idea of how extensive the disease may be, as well as how well organs such as the liver and kidneys are functioning. Tests of fluid and tissue samples A person's symptoms and the results of exams, imaging tests, and/or blood tests may strongly suggest that mesothelioma is present, but the actual diagnosis is made by removing cells from an abnormal area and looking at them under a microscope. This is known as a biopsy. It may be done in different ways, depending on the situation. Thoracentesis, paracentesis, and pericardiocentesis If you have a buildup of fluid in the body that may be related to mesothelioma, a sample of this fluid can be removed by inserting a long, hollow needle through the skin and into the fluid and removing it. Numbing medicine is used on the skin before the needle is inserted. This may be done in a doctor's office or in the hospital. This procedure has different names depending on where the fluid is: • Thoracentesis removes fluid from the chest cavity. • Paracentesis removes fluid from the abdomen. • Pericardiocentesis removes fluid from the sac around the heart. The fluid is then tested to see its chemical makeup and is looked at under a microscope to see if there are cancer cells in the fluid. If cancer cells are present, special tests can determine if the cancer is a mesothelioma, a lung cancer, or another type of cancer. Not finding any cancer cells in the fluid does not necessarily mean there is no cancer, as not all fluid may contain cancer cells. In many cases, doctors need to get an actual sample of the pleural or peritoneal tissue to determine if mesothelioma is present. Needle biopsies Suspected tumors in the chest are sometimes sampled by needle biopsy. A long, hollow needle is passed through the skin in the chest between the ribs and into the pleura. Imaging tests such as CT scans are used to guide the needle into the tumor so that a small sample can be removed to be looked at under the microscope. This procedure is also done without a surgical incision or overnight hospital stay. In some cases, the sample removed may not be big enough to make an accurate diagnosis, and a more invasive biopsy method may be needed. A possible complication of this approach is the buildup of air between the lung and the chest wall, which is known as a pneumothorax. In some cases this can lead to the collapse of part of a lung, causing shortness of breath. If this happens, it can be treated by temporarily placing a suction tube through the skin and into the chest, which will re-expand the lung. Thoracoscopy, laparoscopy, and mediastinoscopy In most cases, a tissue sample of a pleural or pericardial tumor can be obtained using a technique called thoracoscopy. Most often this is done in the operating room while you are under general anesthesia (in a deep sleep). The doctor inserts a thin, lighted tube with a small video camera on the end (a thoracoscope) through a small cut made in the chest wall to view the space between the lungs and the chest wall. (Sometimes more than one cut is made.) Using this, the doctor can see potential areas of cancer and remove small pieces of tissue to look at under the microscope. Thoracoscopy can also be used to sample lymph nodes and fluid and assess whether a tumor is growing into nearby tissues or organs. Similarly, laparoscopy can be used to see and obtain a biopsy of a peritoneal tumor. In this procedure, a flexible tube containing a small video camera is inserted into the abdominal cavity through small cuts on the front of the abdomen. If imaging tests such as a CT scan suggest that the cancer may have spread to the lymph nodes between the lungs, the doctor may do a procedure called a mediastinoscopy. This is also done in an operating room while you are under general anesthesia (in a deep sleep). A small cut is made in the front of the neck above the breastbone (sternum) and a thin, hollow, lighted tube is inserted behind the sternum. Special instruments can be passed through this tube to take tissue samples from the lymph nodes along the windpipe and the major bronchial tube areas. Cancers in the lung often spread to lymph nodes, but mesotheliomas do this less often. Tests on lymph nodes can give the doctor information on whether a cancer is still localized or if it has started to spread, and can help distinguish lung cancer from mesothelioma. Surgical biopsy In some cases, more invasive procedures may be needed to get a large enough tissue sample to make a diagnosis. Surgery, either a thoracotomy (which opens the chest cavity) or a laparotomy (which opens the abdominal cavity), allows the surgeon to remove a larger sample of tumor or, sometimes, to remove the entire tumor. Bronchoscopic biopsy If you might have pleural mesothelioma, the doctor may also do a bronchoscopy. The doctor passes a long, thin, flexible, fiber-optic tube called a bronchoscope down the throat to look at the lining of the lung's main airways. You will be sedated for this. If a tumor is found, the doctor can take a small sample of the tumor through the tube. Testing the samples in the lab No matter which approach used to obtain them, biopsy and fluid specimens are sent to the pathology lab. There, a doctor will look at them under a microscope and do other tests to determine if cancer is present (and if so, what type of cancer it is). It is often hard to diagnose mesothelioma by looking at the cells from the fluid around the lungs, abdomen, or heart. It is even hard to diagnose mesothelioma with tissue from small needle biopsies. Under the microscope, mesothelioma can look like several other types of cancer. For example, pleural mesothelioma may resemble some types of lung cancer, and peritoneal mesothelioma may look like some cancers of the ovaries. For this reason, special lab tests are often done to help distinguish mesothelioma from some other cancers. These tests often use special techniques to recognize certain markers (types of chemicals) contained in mesothelioma cells. • Immunohistochemistry tests look for different proteins on the surface of the cells. It can be used to tell if the cancer is a mesothelioma or a lung cancer, which can appear to start in the lining of the chest cavity. • DNA microarray analysis is a newer test that actually looks at patterns of genes in the cancers. Mesotheliomas have different gene patterns than other cancers. • Electron microscopy can sometimes help diagnose mesothelioma. The electron microscope can magnify samples more than 100 times greater than the light microscope that is generally used in cancer diagnosis. This more powerful microscope makes it possible to see the small parts of the cancer cells that distinguish mesothelioma from other types of cancer. If mesothelioma is diagnosed, the doctor will also determine what type of mesothelioma it is, based on the patterns of cells seen in the microscope. Mesotheliomas are classified as either epithelioid, sarcomatoid, or mixed/biphasic. Pulmonary function tests Pulmonary function tests (PFTs) may be done after a mesothelioma diagnosis to see how well your lungs are working. This is especially important if surgery is an option in treating the cancer. Because surgical removal of part or all of lung results in lower lung capacity, it's important to know how well the lungs are working beforehand. These tests can give the surgeon an idea of whether surgery may be an option, and if so, how much lung can safely be removed. There are a few different types of PFTs, but they all basically involve having you breathe in and out through a tube that is connected to different machines.
Mesothelioma is most often diagnosed after a patient goes to a doctor because of symptoms. If there is a reason to suspect you may have mesothelioma, your doctor will use one or more tests to find out if the disease is present. Symptoms might suggest that a person may have mesothelioma, but tests are needed to confirm the diagnosis.
Signs and symptoms of mesothelioma
Early symptoms of mesotheliomas are not specific to the disease, and people often ignore them or mistake them for common, minor ailments. Most people with mesothelioma have symptoms for a few months before they are diagnosed, although in some people this is longer.
Symptoms of pleural mesothelioma (mesothelioma of the chest) can include:
•pain in the lower back or at the side of the chest
•shortness of breath
•cough
•fever
•sweating
•fatigue
•weight loss
•trouble swallowing
•hoarseness
•swelling of the face and arms
•muscle weakness
Symptoms of peritoneal mesothelioma can include:
•abdominal (belly) pain
•swelling or fluid in the abdomen
•weight loss
•nausea and vomiting
The symptoms and signs above may be caused by mesothelioma, but they may also be caused by other conditions. Still, if you have any of these problems (especially if have been exposed to asbestos), it's important to see your doctor right away so the cause can be found and treated, if needed.
Medical history and physical exam
If you have any signs or symptoms that suggest you might have mesothelioma, your doctor will want to take a complete medical history to check for symptoms and possible risk factors, especially asbestos exposure. You will also be asked about your general health.
A physical exam can provide information about possible signs of mesothelioma and other health problems. Patients with pleural mesotheliomas often have fluid in their chest cavity (pleural effusion) caused by the cancer. Fluid can build up in the abdominal cavity (ascites) in cases of peritoneal mesothelioma, or in the pericardium (pericardial effusion) in cases of pericardial mesothelioma. Rarely, mesothelioma can develop in the groin and look like a hernia. All of these might be found during a physical exam.
If symptoms and/or the results of the physical exam suggest a mesothelioma might be present, more involved tests will likely be done. These might include imaging tests, blood tests, and other procedures.
Imaging tests
Imaging tests use x-rays, radioactive particles, or magnetic fields to create pictures of the inside of your body. Imaging tests may be done for a number of reasons, including to help find a suspicious area that might be cancerous, to learn how far cancer may have spread, and to help determine if treatment has been effective.
Chest x-ray
This is often the first test done if someone has symptoms such as a constant cough or shortness of breath. It may show an abnormal thickening of the pleura, calcium deposits on the pleura, fluid in the space between the lungs and the chest wall, or changes in the lungs themselves as a result of asbestos exposure. These findings may also suggest a mesothelioma.
Computed tomography (CT) scan
The CT scan is an x-ray procedure that produces detailed cross-sectional images of your body. Instead of taking one picture, like a regular x-ray, a CT scanner takes many pictures as it rotates around you while you are lying on a narrow platform. A computer then combines these into images of slices of the part of your body that is being studied.
CT scans are often used to help assess the likelihood that mesothelioma is present and help determine the exact location of the cancer. They can also help stage the cancer (determine the extent of its spread). For example, they can show if the cancer has spread to the liver or other organs. This can help to determine if surgery might be a treatment option. Finally, CT scans can be used to determine if treatment such as chemotherapy has been helpful in shrinking or slowing the growth of the cancer.
Prior to the scan, you may be asked to drink a contrast solution and/or get an intravenous (IV) injection of a contrast dye that helps better outline abnormal areas in the body. You may need an IV line through which the contrast dye is injected. The injection can cause some flushing (redness and warm feeling). Some people are allergic and get hives or, rarely, more serious reactions like trouble breathing and low blood pressure. Be sure to tell the doctor if you have ever had a reaction to any contrast material used for x-rays.
You need to lie still on a table while the scan is being done. During the test, the table moves in and out of the scanner, a ring-shaped machine that completely surrounds the table. You might feel a bit confined by the ring you have to lie in while the pictures are being taken.
In recent years, spiral CT (also known as helical CT) has become available in many medical centers. This type of CT scan uses a faster machine. The scanner part of the machine rotates around the body continuously, allowing doctors to collect the images much more quickly than standard CT. As a result, you do not have to hold your breath for as long while the image is taken. This lowers the chance of blurred images occurring as a result of breathing motion. It also lowers the dose of radiation received during the test. The slices it images are thinner, which yields more detailed pictures.
