Chapter 9
1. Which common childhood disorder requires a genetic contribution and a significant environmental contribution to develop fully? A. Achondroplasia B. Sickle cell disease C. Type 1 diabetes mellitus D. von Willebrand disease
1. ANS: C Achondroplasia, sickle cell disease, and von Willebrand disease have strong genetic causes that require minimal environmental input to develop fully. The susceptibility to development of type 1 diabetes is genetic, but an environmental insult, such as a viral infection, is needed for the disease to develop.
10. Which type of testing is most commonly used to diagnose cystic fibrosis? A. Mucus protein electrophoresis B. Genetic mutation analysis C. Sweat chloride analysis D. Stool analysis
10. ANS: C Genetic testing is not used to diagnose the homozygous expression of CF. It is diagnosed on the basis of physical manifestations and the results of the sweat chloride test. Positive results are those indicating a high concentration of sodium chloride in the person's sweat (60 to 200 mEq/L or mmol/L) compared with the normal value (5 to 35 mEq/L). Genetic testing by direct sequencing of the CFTR gene is useful for establishing carrier status, identifying affected children prenatally, and, to some degree, predicting disease severity but is not used as primary diagnostic testing.
11. Which relative of a patient who has cystic fibrosis has the correct risk for being a cystic fibrosis carrier? A. Sister 0% B. Mother 50% C. Father 100% D. Brother 100%
11. ANS: C Cystic fibrosis is inherited as an autosomal recessive single gene trait. Therefore, in virtually all cases, both parents are carriers. A patient's brother and sister would each have a 50% risk for being carriers.
12. Which tissues are most commonly affected by mutation of the CFTR gene? A. Eyes and ears B. Brain and intestines C. Lungs and pancreas D. Kidneys and long bones
12. ANS: C The two main organ systems affected involve epithelial cells and are the lungs and the pancreas. The epithelial cells in these tissues produce a thick, sticky mucus as a result of poor chloride transport that, over time, plugs up the glands in these organs, causing glandular atrophy and organ dysfunction or failure. Other organs that are affected to a far lesser degree include the liver, salivary glands, and testes.
13. What is the most likely explanation for the variability in expression of disease severity for cystic fibrosis? A. The ethnicity of the patient B. The specific CFTR gene mutation inherited C. The presence of other nongenetic lung or pancreatic problems D. The length of trinucleotide repeat sequences in the first exon of the CFTR gene
13. ANS: B The specific mutation inherited in cystic fibrosis can make a big difference in the severity of symptoms. There are well over 1000 different mutations, and some cause milder clinical signs and symptoms. The ethnicity of the patient is not relevant. CF is an autosomal recessive single gene trait, making triplet repeats not relevant. Although nongenetic liver or pancreatic problems in a person with CF could make some symptoms worse, this is not a common cause of variability in the severity of CF symptoms.
14. What health advantage does cystic fibrosis confer on the person who has it? A. Decreased risk for type 1 diabetes mellitus B. Decreased risk for tuberculosis C. Decreased risk for anemia D. Decreased risk for cholera
14. ANS: D The high frequency of the heterozygous carrier state for CF among Caucasians from Northern and Western Europe suggests that being a CF carrier might have a potential advantage. Scientists now believe people who are heterozygous or homozygous for specific common CFTR mutations have greater resistance to typhoid and to cholera toxin when exposed to these disease-causing microorganisms.
15. Why does Duchenne muscular dystrophy (DMD) have poor reproductive fitness? A. Most affected individuals typically do not have children. B. Fifty percent of mutations of the dystrophin gene are deletions. C. The loss of functional adhesion proteins prevents reproduction. D. The expression of disease severity is highly variable among adults.
15. ANS: A Most patients with DMD will die in the late teenage years or early adulthood, and they do not typically have children. There is little variability in the severity of DMD. Those with milder cases are thought to have Becker muscular dystrophy. While deletions are possible, the dystrophin gene is so large that it is an easy target for a variety of mutations. Adhesion proteins are not involved.
16. What is the explanation for creatine kinase (CK) levels in a 14-year-old boy with Duchenne muscular dystrophy being much lower now than they were 5 years ago? A. His disease is improving. B. He now performs passive rather than active exercise. C. Most of the muscle tissue has already been destroyed. D. The disease is probably Becker muscular dystrophy rather than Duchenne muscular dystrophy.
16. ANS: C Children with DMD have hugely elevated blood levels of the enzyme creatine kinase (CK) and the protein myoglobin during their early childhood years. Both are normally present inside intact muscle cells. When the cells are damaged or die, CK and myoglobin are released into the blood. These levels decrease as the child ages because there is a limit to how much muscle is available to be destroyed. Therefore, lower levels in older children indicate disease progression, not disease improvement. Switching to passive exercise does not decrease muscle damage. BMD has a slower rate of muscle destruction with a more consistent level of blood CK over time.
17. Which additional health problem commonly develops in boys with Duchenne muscular dystrophy? A. Arthritis B. Hypertension C. Diabetes mellitus D. Chronic heart failure
17. ANS: D Most boys with DMD develop cardiac muscle problems because these cells also rely on dystrophin to maintain their integrity. The most common problems are dilated cardiomyopathy and chronic heart failure. There are fewer problems with smooth muscle. Those that are present do not cause vasoconstriction. Thus hypertension is not a common problem. The muscles rather than joints are affected and arthritis does not develop. There is no known association of DMD with the development of diabetes.
18. A 21-year-old woman who has two brothers with Duchenne muscular dystrophy asks whether carrier status testing is appropriate for her. What is the best response? A. "Testing could be beneficial because your risk for being a carrier is nearly 100%." B. "Testing could be beneficial because your risk for being a carrier is approximately 50%. C. "Testing is not necessary because you would have expressed some symptoms of the disease by this time if you were a carrier." D. "Testing is not necessary because the spontaneous mutation rate for this genetic problem is high and likely to be why your brothers have the disease."
18. ANS: B The genetic mutation for Duchenne muscular dystrophy is on the X chromosome and is transmitted in an X-linked recessive manner. Although the spontaneous mutation rate for this disease is relatively high, the fact that she has two brothers with the disorder rather than just one strongly suggests this mutation was inherited, not spontaneous. Thus, her mother is a carrier of an X-linked recessive genetic mutation. This young woman's risk for having inherited the mutation on her maternally derived X chromosome is 50%, not 100%. If she were a carrier, she may or may not have any symptoms of the disorder depending on which X is inactivated in her skeletal muscle and cardiac muscle tissues. The absence of symptoms does not clearly rule out a carrier status for her.
19. Zoe, a 20-year-old woman, shows signs of mild muscle weakness. She has two first cousins on her mother's side who died of Duchenne's muscular dystrophy (DMD). Which explanation regarding Zoe's situation is most likely? A. Zoe is a heterozygote showing partial expression. B. Zoe and her cousins shared similar environmental risks. C. The muscle weakness is related to Zoe's lack of exercise in her "girly-girl" lifestyle. D. Zoe is homozygous for DMD, with a defective dystrophin gene inherited from both parents.
19. ANS: A Some female carriers of DMD show partial gene expression and can demonstrate symptoms of the disease. It is very likely that she is a carrier because this X-linked recessive disease has been seen in her family. It is highly unlikely that she would have received two defective dystrophin genes from her parents because men with DMD tend not to father children.
2. Which ethnic group has the highest incidence of sickle cell disease? A. Ashkenazi Jews B. Asian Americans C. African Americans D. French Canadians from Quebec
2. ANS: C The disorder is inherited as an autosomal recessive single gene trait and is most common among people with African or other equatorial ancestry. The incidence of SCD in the United States among African Americans is about 1 in 400 live births. Carrier status, in which a person has only one mutated beta globin gene allele is estimated at 1 in 15 African Americans. Both SCD and sickle cell trait have a far greater incidence in East Africa and other equatorial countries.
____ 20. Which statement regarding classic hemophilia is true? A. Females are not affected. B. Because hemophilia is X-linked recessive, females are affected and males are carriers. C. Because hemophilia is X-linked recessive, males are affected and females are carriers. D. The sons of women who are older than age 40 when pregnant are at an increased risk for hemophilia.
20. ANS: C The F8 gene is located on the X chromosome (Xq28). Because males have only one X chromosome, which is inherited exclusively from their mothers, hemophilia has a sex-linked (X-linked) transmission pattern. Males are either affected or unaffected; they cannot be carriers. Few females are born with classic hemophilia because the disease is so severe in the homozygous state that these individuals die during early embryonic life. Females can be carriers. Most female carriers of classic hemophilia have reduced levels of factor VIII and have excessive bruising and bleeding. Although the spontaneous mutation rate for the gene causing this disorder is relatively high, it is not related to advanced maternal age.
21. Which type of testing is most commonly used to diagnose classic hemophilia? A. Hematocrit and hemoglobin levels B. X-chromosome inactivation C. Genetic mutation analysis D. Factor VIII levels
21. ANS: D Genetic testing is not used to diagnose classic hemophilia. It is diagnosed on the basis of physical manifestations and low levels of Factor VIII. Hematocrit and hemoglobin levels are not specifically diagnostic for hemophilia. X-chromosome inactivation does not occur in males. Carriers can be identified by the presence of lower than normal levels of factor VIII, longer than average PTT, and F8 gene sequencing to determine the presence or absence of the specific mutation identified within the family.
22. Which statement regarding type 1 von Willebrand disease (VWD) is true? A. Incomplete or reduced penetrance is common. B. It represents a female form of classic hemophilia. C. Carriers can transmit the disease to their children. D. Males are affected twice as frequently as females
22. ANS: A The VWF gene is located on an autosome, chromosome 12. Type 1 VWD is inherited in an autosomal dominant pattern; however, because of reduced penetrance, at times a family pedigree can give the appearance of an autosomal recessive pattern, although there is not a true carrier status. With reduced penetrance, a person who does not manifest the disorder can transmit the affected gene to his or her children who then may express the disorder. Males and females are affected equally.
23. A son with achondroplasia is born to parents with no family history of the disease. What is the most likely explanation for the son's disorder? A. The son is not biologically related to the father. B. The son is not biologically related to the mother. C. The gamete of one parent had a spontaneous mutation. D. The son's DNA underwent a spontaneous mutation during the second trimester of pregnancy.
23. ANS: C Achondroplasia follows an autosomal dominant transmission pattern, although spontaneous mutations are responsible about 75% to 80% of the time. It is very common for a child with achondroplasia to be born to parents without the disorder and who have no other family members with the problem.
24. Which phenotypic feature associated with achondroplasia has variable expression? A. Disproportionally short extremities B. Larger than average head size C. Prominent forehead D. Hydrocephaly
24. ANS: D Most of the physical features of achondroplasia, including disproportionately short extremities, large head, and prominent forehead, are present in all individuals who have the disorder. One variable feature is hydrocephaly. This occurs in some but not all children with the disorder.
25. Which factor has the greatest influence in the development of type 1 diabetes mellitus? A. Inheritance of the HLA-DR or HLA-DQ tissue types B. Sedentary lifestyle coupled with childhood obesity C. Mutation in the gene for pancreas development D. Advanced maternal age at conception
25. ANS: A Susceptibility to development of type 1 diabetes as an autoimmune problem is partially determined by inheritance of human leukocyte antigen (HLA) genes coding for the HLA-DR and HLA-DQ tissue types located on chromosome 6. However, this complex disorder also requires an environmental interaction, most often in the form of a viral infection. Sedentary lifestyle and childhood obesity are not associated with type 1 DM, just type 2. The disorder is not related to faulty pancreatic development of genetic origin. It is not related to advanced maternal age.
26. Which result of genetic/genomic variation has the most support as a cause of asthma? A. Decreased resistance to infectious microorganisms B. Early childhood exposures to inhalation irritants (air pollution) C. Increased inflammatory responses to environmental triggers D. Mutations of frontal lobe genes controlling attention-getting behavior
26. ANS: C Common areas of identified genomic variation associated with atopic asthma include those areas that contain genes coding for proteins that are important in regulating inflammatory reactions and immune responses. One of the strongest associations currently identified with susceptibility to asthma involves eight to twelve different single nucleotide polymorphisms at the 1q31 locus, encoding the gene DENND1B, which produces a protein strongly active in the work of two dendritic-type cells of the immune system, the macrophage and the mast cell. Both of these cell types are involved in nonspecific inflammatory responses and in acquired (adaptive) immune responses that develop individually in susceptible people when they are exposed to an allergen.
27. Which type of gene could be considered a "candidate gene" for mutations that increase the genetic input to asthma development? A. One that controls the expression of hemoglobin levels B. One that regulates the number of alveoli a person develops C. One that regulates the sensitivity of bronchiolar smooth muscle D. One that is responsible for the metabolism and elimination of nicotine
27. ANS: C Asthma is a disease of the airways that is characterized by intermittent reversible airflow obstruction and is not a problem of the alveoli. It can occur as a result of any or all of these three actions: (1) constriction of the smooth muscles surrounding the smaller airways, (2) swelling of the mucous membranes lining the airways, or (3) excessive mucus collecting in and plugging the airways. Hemoglobin partially determines the ability of red blood cells to carry oxygen and has nothing to do with airways. Although nicotine can cause constriction of bronchial smooth muscle, a problem in the ability to metabolize and eliminate nicotine is not related to the development of asthma.
3. Which type of testing is most commonly used to diagnose sickle cell disease? A. Hematocrit and hemoglobin levels B. Hemoglobin electrophoresis C. Genetic mutation analysis D. Sweat chloride analysis
3. ANS: B Genetic mutation testing is not used to diagnose SCD. It is diagnosed based on the large percentage of hemoglobin S (HbS) seen on electrophoresis. A person who has SCD usually had 80% to 90% HbS, and a person with sickle cell trait usually has less than 40% HbS. Although hemoglobin and hematocrit levels may be abnormal, they alone are not diagnostic for sickle cell disease. Sweat chloride levels are abnormal in people with cystic fibrosis and normal in people with sickle cell disease.
4. Which specific type of genetic problem causes sickle cell disease? A. Deletion of an exon B. Deletion of an intron C. Unbalanced translocation D. Single nucleotide polymorphism
4. ANS: D Sickle cell disease (SCD) is a genetic disorder caused by a single nucleotide polymorphism in both alleles of a single gene, which results in the abnormal formation of the beta chain of hemoglobin (beta globin). In the classic form of sickle cell disease, both beta globin alleles have a mutation in which the DNA triplet coding for glutamic acid has adenine substituted for thymine (instead of CTC, the triplet now reads CAC). This mutation results in valine as the sixth amino acid in the protein sequence. There is no deletion of introns or exons, nor is there a translocation (balanced or unbalanced).
5. How is sickle cell trait different from sickle cell disease? A. People with sickle cell disease are homologous for the mutation, whereas those with sickle cell trait are heterozygous for the mutation. B. People with sickle cell trait are homologous for the mutation, whereas those with sickle cell disease are heterozygous for the mutation. C. Sickle cell disease results from an inherited mutation, and sickle cell trait results from an acquired mutation. D. Sickle cell trait results from an inherited mutation, and sickle cell disease results from an acquired mutation.
5. ANS: A When only one beta globin allele has the mutation, the person is heterozygous for the mutation and has sickle cell trait. In this disorder, the percentage of HbS in RBCs is usually less than 40%. When both alleles of the beta globin gene are mutated, the person is homozygous for the mutation and has sickle cell disease. RBCs have a high percentage, close to 90%, of hemoglobin S (HbS) rather than HbA.
6. How does hydroxyurea reduce the manifestations of sickle cell disease? A. Promoting red blood cell production B. Increasing the concentration of fetal hemoglobin (HbF) C. Relaxing vascular smooth muscle so that blood flow to critical tissues and organs is improved D. Correcting the mutation of one allele so the person has sickle cell trait instead of sickle cell disease
6. ANS: B One of the best predictors for which patients who have SCD will have delayed complications is the percentage of fetal hemoglobin (HbF) that remains in circulation. Hydroxyurea increases the percentage of HbF in anyone who receives it, including a person with SCD. The drug does not correct genetic mutations, nor does it promote red blood cell production or vascular smooth muscle relaxation.
7. What health advantage does sickle cell trait or disease confer on the person who has it? A. Decreased risk for type 1 diabetes mellitus B. Decreased risk for hypercholesterolemia C. Decreased risk for fulminating cholera D. Decreased risk for malaria
7. ANS: D The hemoglobin change caused by the genetic mutation of SCD does reduce the susceptibility to severe malaria on exposure or infection with the organism. This benefit occurs in both those who are homozygous for the gene mutation and in those who are heterozygous. The disorder does not provide a benefit or reduce risk for development of type 1 diabetes, hypercholesterolemia, or cholera.
8. A woman whose hemoglobin S levels are less than 1% has a brother with sickle cell disease and both parents have been diagnosed as carriers for the disorder. She asks what her risks are of having a child with sickle cell disease. What is the best response? A. "Because you do not have the trait, you cannot have a child with sickle cell disease regardless of your partner's sickle cell status." B. "Because both your parents have the trait, it is possible for you to have a child with sickle cell disease if your partner actually has the disease." C. "Because your brother actually has sickle cell disease, the risk for your children having sickle cell disease is 50% with each pregnancy." D. "Because you are a woman, your daughters will each have a 50% risk for having the disease and all of your sons will be carriers of the trait."
8. ANS: A Sickle cell disease is an autosomal recessive genetic disorder. This woman does not have either sickle cell disease or sickle cell trait, as evidenced by the fact that her HbS levels are less than 1%. Thus, regardless of her partner's sickle cell status, she will not have a child with actual sickle cell disease. However, if her partner is a carrier, any child she has with this partner has a 50% risk of having sickle cell trait. If her partner has sickle cell disease, any child she has will be a carrier of sickle cell trait.
9. Which ethnic group has the highest incidence of cystic fibrosis? A. Asian Americans B. African Americans C. Hispanic Americans D. European Americans
9. ANS: D The disorder is inherited as an autosomal recessive single gene trait and is most common among Caucasians of Northern and Western European heritage, although it can be found among people of all races and ethnicities. The incidence of CF in the United States among Caucasians is about 1 in 3000 live births. Carrier status in which a person has only one mutated gene allele is estimated at 1 in 20 to 30 Caucasian Americans.
