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1. Phenylketonuria-Individuals with this disorder are unable to produce the enzyme responsible for the conversion of the amino acid phenylalanine to the amino acid tyrosine. Because tyrosine is needed in the production of melanin, PKU sufferers are very blond and fair -skinned. Phenylalanine is present in protein and in the artificial sweetener aspartamine (equal). Phenylalanine builds up in the body and acts as a neurotoxin causing brain damage and mental retardation. Most states require that all newborns be tested for the presence of this disorder. Afflicted individuals are placed on a special diet that is extremely low in phenylalanine. Strict adherence to this diet can prevent the brain damage and mental retardation. The diet can be discontinued once the brain is completely formed. The actual age at which the diet can be safely discontinued (at the age of 6 versus following adolescence) is controversial. As a result of early detection and treatment, adults with this disorder may have a normal phenotype. PKU is caused by a recessive allele (p). Therefore, only individuals homozygous for the allele will develop the disorder.
Assume a man homozygous for PKU marries a woman who is heterozygous for PKU.
1. What is the genotype of the man? __________
2. What is the genotype of the woman? _________
3. What is the probability that their child will have PKU? _________
4. What is the probability that their child will not have PKU? _________
5. What is the probability that their child will not be a carrier for PKU? _______
6. What is the probability that their child is a carrier (carries but does not have the disease)? _________
7. Would you predict that this genetic defect will become more common or less common in the future? _________ Explain your answer.

2. Cystic Fibrosis-Individuals with cystic fibrosis have a genetic defect that interferes with secretory processes. As a result they produce excessive amounts of thick mucus that clog the respiratory passages providing a breeding ground for respiratory disease. Digestive processes are also impaired because the disease causes blockage of the ducts carrying pancreatic digestive enzymes and bile to the intestines. They also produce excessively salty sweat. In cystic fibrosis, the defective gene normally codes for CFTR protein (cystic fibrosis transmembrane conductance regulator protein). This protein functions as a chloride channel controlling the flow of chloride ions in and out of the cells. Because of the genetic defect the CFTR protein is not
made correctly. This is an example of pleiotropy (single allele has more than one phenotypic effect). Researchers are currently investigating the use of genetic engineering (using disabled cold viruses to carry normal CFTR genes into the respiratory system), activating the defective protein, and prodding a different protein to take on the responsibilities of the CFTR protein. Scientists have reversed cystic fibrosis in mice by feeding them DHA (decosahexaenoic acid), a fatty acid found in fish oil. Human tests began this year (2000). Cystic fibrosis is the most common lethal genetic disease in the U.S. It is most common in white children (1 in 2400 white children). It is interesting that carriers (heterozygotes) are protected from the deadly effects of diarrhea caused by cholera. Cystic fibrosis is caused by a recessive allele (f).
A man who is heterozygous for cystic fibrosis marries a woman who has a normal genotype.
1 What is the genotype of the man? ______
2 What is the genotype of the woman? ______
3 What is the probability that they will produce a child with cystic fibrosis? _______
4 What is the probability that they will produce a child who is a carrier for cystic fibrosis (heterozygous)? ________
5 What is the probability that they will produce a child that has a normal genotype? ________

3. Huntington's Disease-Individuals with Huntington's disease have massive degeneration of the basal nuclei in the brain leading to wild involuntary movements and progressing to dementia and death. This disease is caused by repeats of the CAG codons near the end of chromosome 4. Perhaps 1 in 24,000 individuals develops the disorder. It is caused by a dominant allele so that every individual who inherits the allele will eventually develop the disease. Symptoms do not usually appear until after the age of 30. Huntington's Disease is lethal to the embryo in the homozygous condition.
A couple has been married for five years and are planning to conceive their first child when they learn that the man's father has Huntington's Disease. Assume that both the man's wife and his mother are normal.
1. What is the man's father's genotype? __________
2. What is the wife's genotype? _________
3. What will the man's genotype be if he has inherited the disease from his father? ____________
4. What is the probability that the man has inherited the disease from his father? ______
5. What is the probability that the couple will have a child with Huntington's Disease if the man has inherited the disease? _______
6. Most lethal genetic diseases that are caused by a single gene are recessive. Lethal recessive alleles are able to hide in heterozygous individuals. Natural selection can only weed out the unfavorable allele when it is expressed in an individual homozygous for the allele. A lethal allele that is dominant kills every individual that inherits it. Therefore these dominant alleles are removed from the population before they can be passed on to the next generation. Why do you think Huntington's Disease can not be wiped out by natural selection?

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