B.6.E identify and illustrate changes in DNA and evaluate the significance of these changes
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1 B.6.E identify and illustrate changes in DNA and evaluate the significance of these changes One look around a room tells you that each person has slight differences in their physical make up and therefore in their DNA. These subtle variations in DNA are called polymorphisms (literally "many forms"). Many of these gene polymorphisms account for slight differences between people such as hair and eye color. But some gene variations may result in disease or an increased risk for disease. Although all polymorphisms are the result of a mutation in the gene (specifically a change in the DNA), geneticists only refer to a change as a mutation when it is not part of the normal variations between people. What Causes DNA Mutations? Everyone acquires some changes to their DNA during the course of their lives. Mutations in DNA sequences generally occur through one of two processes. These changes occur in a number of ways. 1. DNA damage from environmental agents such as ultraviolet light (sunshine), nuclear radiation or certain chemicals. Other changes are introduced as a result of DNA damage through environmental agents including sunlight, cigarette smoke, and radiation. Our cells have built in mechanisms that catch and repair most of the changes that occur during DNA replication or from environmental damage. As we age, however, our DNA repair does not work as effectively and we accumulate changes in our DNA.
2 2. Mistakes that occur when a cell copies its DNA in preparation for cell division. Sometimes there are simple copying errors that are introduced when DNA replicates itself. (Every time a cell divides, its entire DNA is duplicated so that the each of the two resulting cells have a full set of DNA.) Some of these changes occur in body cells such as in skin cells as a result of sun exposure but are not passed on to children. But other errors can occur in the DNA of cells that produce the eggs and sperm. These are called germline mutations and can be passed from parent to child. If a child inherits a germline mutation from their parents, every cell in their body will have this error in their DNA. Germline mutations are what cause diseases to run in families, and are responsible for the kind of hereditary diseases covered by Genetic Health. What Kind of Mutations Are There When DNA Replicates? A gene is essentially a sentence made up of the bases A, T, G, and C that describes how to make a protein. Any changes to those instructions can alter the gene's meaning and change the protein that is made, or how or when a cell makes that protein. There are many different ways to alter a gene, just as there are many different ways to introduce typos into a sentence. In the following examples of some types of mutations, we use the sentence "The fat cat ate the wee rat" as a sample gene: Point Mutation A point mutation is a simple change in one base of the gene sequence. This is equivalent to changing one letter in a sentence, such as this example, where we change the 'c' in cat to an 'h': Original The fat cat ate the wee rat. Point Mutation The fat hat ate the wee rat. Frame-shift mutation In a frame shift mutation, one or more bases are inserted or deleted, the equivalent of adding or removing letters in a sentence. But because our cells read DNA in three letter "words", adding or removing one letter changes each subsequent word. This type of mutation can make the DNA meaningless and often results in a shortened protein. Insertion Mutations that result in the addition of extra DNA are called insertions. Insertions can also cause frameshift mutations, and general result in a nonfunctional protein. Insertion The fat cat xlw ate the wee rat.
3 An example of a frame-shift mutation using our sample sentence is when the 't' from cat is removed, but we keep the original letter spacing: Frame Shift The fat caa tet hew eer at. Deletion Mutations that result in missing DNA are called deletions. These can be small, such as the removal of just one "word," or longer deletions that affect a large number of genes on the chromosome. Deletions can also cause frameshift mutations. In this example, the deletion eliminated the word cat. Deletion The fat ate the wee rat. Inversion In an inversion mutation, an entire section of DNA is reversed. A small inversion may involve only a few bases within a gene, while longer inversions involve large regions of a chromosome containing several genes. Insertion The fat tar eew eht eta tac. There are many types of mutations that change not the protein itself but where and how much of a protein is made. These types of changes in DNA can result in proteins being made at the wrong time or in the wrong cell type. Changes can also occur that result in too much or too little of the protein being made. In most cases, such DNA changes either have no effect or cause harm, but occasionally a mutation can improve an organism's chance of surviving and passing the beneficial change on to its descendants.
4 Examples of Some Genetic Diseases Caused By Mutations in Humans The Gene Associated with Sickle Cell Anemia is caused by a single base change, a substitution of Thymine for Adenine in the DNA. Notice the picture below. The hemoglobin molecule is 146 amino acids long and the DNA change causes a change in only one of the amino acids in the change. This causes a very serious disease where red blood cells die very quickly (they live 10 to 20 days) and also the red blood cells are shaped like a sickle and make log jams in the small blood vessels. The Gene Associated with Cystic Fibrosis is caused by the deletion of 3 base pairs. The protein that the gene codes for is 1480 amino acids long. The lose of these 3 base pairs deletes one of the amino acids at position 508 this causes the mucus in the lungs and digestive system to be very thick (viscous) instead of watery. This thick mucus to builds up in the lungs and block the absorption of oxygen. It also blocks some of the digestive enzymes from getting to the intestines. A patient suffers from the lack of oxygen and malnutrition. Hemophilia's main symptom is bleeding. Defects in blood coagulation factors result in low levels of fibrin, which impairs the body's ability to create strong blood clots.
5 Mutations in the F8 gene cause a type of hemophilia called hemophilia A. Hundreds of mutations in this gene have been identified, including frequent changes that substitute one base pair (the building components of DNA) for another somewhere in the gene. Deletions or insertions of multiple base pairs are also possible. The most common mutation in people with severe hemophilia A is an inversion (a rearrangement that reverses the order of a stretch of DNA) that affects a large part of the gene. Tay-Sachs disease (pronounced tay-sacks) is a genetic disorder that can lead to paralysis, blindness, convulsions, mental retardation (see mental retardation entry), and death. A genetic disorder is a medical problem passed down from one generation to the next. The disorder occurs because of a faulty gene. In a person with Tay- Sachs disease, the enzyme needed to break down gangliosides is missing. As a result, gangliosides continue to build up in the brain. When the brain becomes clogged with this fatty material it is no longer able to function normally. Of the more than 100 mutations identified to date, the vast majority are associated with insertions or deletions of a single base pair. All the small insertions or deletions producing frameshifts and the nucleotide substitutions producing stop codons result in the enzyme not being produced. Cancer is a disease in which cells of an organ or tissue in the body become abnormal, failing to respond to normal growth control mechanisms and continue to grow and multiply out of control. When cells grow out of control they usually form a mass, called a tumor. Some tumors grow and enlarge only at the site where they begin and these are referred to as benign tumors. Other tumors not only enlarge locally, but also have the potential to invade and destroy the normal tissue around them and to spread to distant parts of the body. These tumors are called malignant tumors or cancers. Mutations in Plants In plant pathology, we are most often concerned with mutations that affect pathogen virulence or sensitivity to fungicides or antibiotics. In pathogens that show a genefor-gene interaction with plants, we are especially interested in the mutation from avirulence to virulence because this is the mutation that leads to a loss of genetic resistance in both agroecosystems and natural ecosystems. But mutations from fungicide sensitivity to fungicide resistance also are important in agroecosytems, as are any mutations that affect fitness. Smooth pigweed has survived applications of sulfonylurea (SU) and imidazolinone (IMI) herbicides in a single season. Therefore our herbicides are no longer effective. A plant called Arabidopsis is a small plant that forms tiny seeds. Scientists like this plant because it is easy to grow. A mutation of this plant inactivates a gene that codes for a protein that helps the plant get iron from the soil. Without this protein,
6 the mutant plant grows slower and turns yellow because it has trouble getting iron from the soil. Consider the barley powdery mildew pathogen Blumeria graminis f. sp. hordei. A mature spore producing powdery mildew plant produces ~10 4 spores per day. If 10% of the barley leaf area in a field is infected, there are approximately 10 5 spores per square meter in the field, and the daily spore production is approximately 10 9 spores per square meter or spores per hectare per day. With a mutation rate of 10-6 at avirulence loci, there would be approximately 10 7 virulent mutant spores produced in each hectare each day. These virulent mutants can travel out of a field planted to a susceptible barley cultivar and infect a neighboring field planted to a resistant barley cultivar. The virulent mutants that have lost the elicitor encoded by the avirulence allele can infect the resistant cultivar and produce a new generation of virulent progeny. This process appears to have happened many times with powdery mildew and rust fungi in agricultural ecosystems, leading eventually to boom-and-bust cycles. Maize Corn has mutations caused by gene variation. There are some that are a benefit and some that are harmful. One such type is called Lazy Plant which causes the plant to grow horizontally; it will break if straightened up. Another type called sugary produces wrinkled, translucent kernels that are sweet at the milky stage. Most sweet corn is sweet because of this gene.
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