Chapter 1: Background and History

Multiple Choice

1. Achondroplasia has a high mutation rate. This is most likely the result of
2. Paternal age effect
3. Maternal age effect
4. Large gene size
5. Methylated CG dinucleotide
6. None of the above

Answer: d

Correct Feedback: This has been shown to be the cause of achondroplasia.

Incorrect Feedback: This has not been shown to be the cause of achondroplasia.

2. The effect of mutations in the SHOX gene would best be described as
3. Haploinsufficiency
4. Dominant negative
5. Autosomal recessive
6. Gain of function
7. X-linked recessive

Answer: a

Correct Feedback: The effect is best described as haploinsufficiency.

Incorrect Feedback: This does not explain the effects of mutations in the SHOX gene.

3. Which of the following mechanisms is known to cause Prader-Willi syndrome?
4. Chromosome duplication
5. Translocation
6. Uniparental disomy
7. Autosomal trisomy
8. Autosomal monosomy

Answer: c

Correct Feedback: Prader Willi syndrome is affected by genomic imprinting. Thus, uniparental disomy could cause the disease.

Incorrect Feedback: This would not cause Prader Willi syndrome.

4. Suppose you have established that a disease gene is closely linked to a marker whose location is known. Which of the following would not be useful in defining the disease gene’s location?
5. Testing for unmethylated CG islands
6. Existence of a chromosome deletion in a patient
7. Existence of trisomy in a patient
8. DNA sequencing
9. Testing for cross-species conservation

Answer: c

Correct Feedback: This would not be useful in defining the disease gene’s location.

Incorrect Feedback: This could help you find the disease gene’s location.

5. Which of the following is least likely to be seen in a patient with Huntington disease?
6. Dementia
7. Affective disorder
8. New mutation
9. Delayed age of onset
10. Loss of motor control

Answer: c

Correct Feedback: This is rarely seen in Huntington’s disease. It has one of the lowest known mutation rates of all human disease genes, estimated at approximately 1 per 1 million (per locus per generation).

Incorrect Feedback: This is seen with Huntington’s disease.

6. Which of the following is not a characteristic of osteogenesis imperfecta?
7. Locus heterogeneity
8. Allelic heterogeneity
9. Pleiotropy
10. Imprinting
11. Dominant negative mutation effects

Answer: d

Correct Feedback: Imprinting is more common with Prader-Willi and Angelman syndromes.

Incorrect Feedback: This is a characteristic of osteogenesis imperfecta.

7. In which of the following diseases are dominant negative mutation effects seen?
8. Huntington disease
9. Cystic fibrosis
10. Retinoblastoma
11. Marfan syndrome
12. None of the above

Answer: d

Correct Feedback: Marfan syndrome shows dominant negative effects.

Incorrect Feedback: One of the above shows dominant negative effects.

8. Which of the following is not true of Fragile X syndrome?
9. It is associated with methylation
10. It can be diagnosed using a karyotype
11. It is caused by a trinucleotide repeat expansion
12. It displays nearly 100% penetrance
13. None of the above

Answer: d

Correct Feedback: Fragile X syndrome is an X-linked dominant condition with 80% penetrance in males and 30% penetrance in females.

Incorrect Feedback: This is true of Fragile X syndrome.

9. Which of the following diseases follow(s) a “2-hit model”?
10. Osteogenesis imperfecta
11. Adult polycystic kidney disease
12. Cystic fibrosis
13. Retinoblastoma
14. B and D

Answer: e

Correct Feedback: e. Retinoblastoma and Adult polycystic kidney disease both follow a 2-hit model.

Incorrect Feedback: a. Osteogenesis imperfecta does not follow a 2-hit model.b. This is true but is not the only true answer.c. Cystic fibrosis does not follow a 2-hit model.d. This is true but is not the only true answer.

10. The recurrence risk for trisomy 13 is increased by
11. Advanced paternal age
12. 13/15 translocation in one of the parents
13. Extensive methylation of chromosome 13
14. Advanced maternal age
15. B and D

Answer: e