MEDICAL GENETICS EXAM -Version B

Answer questions 1-40 with the SINGLE BET ANSWER.

1. Unbalanced translocations:

A. Result in acrocentric chromosomes

B. Involve homologous chromosomes

C. Are carried by phenotypically normal individuals

D. Involve 4 chromosomal breaks

E. Are usually deleterious

2. A recently married couple requests counseling because they have just learned that they are first

cousins. They are at an increased risk to have affected children with:

A. Autosomal recessive disorders

B. Autosomal dominant disorders

C. Contiguous gene deletion syndromes

D. Chromosomal disorders

E. A and C

3. If a multifactorial disorder exhibits a threshold, it will only .occur if.

A. Only one organ is affected

B. One of the parents mildly manifests the disorder

C. Consanguinity is present

D. The family size is large

E. Sufficient genetic predisposition to the disorder is present

Q4,5,6. Hurler syndrome is an autosomal recessive "storage" disorder in which partially degraded

mucopolysaccharides (MPS) (glycosaminoglycans) accumulate within lysosomes, causing a

clinical phenotype of coarse facies, tightening of joints, thickening of skin and progressive

mental retardation after the age of approximately 6 mon. The basis of the Hurler Syndrome is

deficient activity of the enzyme α iduronidase.

4. Recently, deficient activity of other enzymes has been found to produce a similar clinical

Phenotype. This phenomenon is called:

A. Variable penetrance

B. Variable expression

C. Uniparental disomy

D. Genetic heterozygosity

E. Genetic heterogeneity

5. Sheie syndrome is a milder yet similar mucopolysaccharide storage disease in which deficient

activity of α iduronidase has also been shown. It has been suggested that Hurler and Sheie

syndromes result from different mutations of the α iduronidase gene. If a mother and father

carriers for the Hurler and Sheie mutations respectively, what would be the risk of

their having a child with MPS storage disease? (Assume a child inheriting both mutations

exhibits MPS storage disease)

A. Negligible

B. 12.5%

C. 25%

D. 50%

C. 100%

6. If they had a son with clinical features of MPS storage, he would be called a:

A. Manifesting heterozygote

B. Mixed heterozygote

C. Compound hemizygote

D. Variable heterozygote

E. Compound heterozygote

7. In X-linked dominant inheritance, all of the following statements are true EXCEPT:

A. 2/ daughters of affected mothers are affected

B. All daughters of affected fathers are affected

C. No sons of affected fathers are affected

D. All sons of affected mothers are affected

E) Males are often more severely affected than females

8. All of the following statements about genetic variation in humans are true EXCEPT:

A. Most nucleotide changes do not produce or predispose to a disease

B. Large portions of the may be nonessential

C. Some mutations may never be recognized because they are incompatible with early

human embryogenesis

D. As many as 1 in 10 nucleotides may differ among unrelated individuals

E. Variation among individuals is due to differences in single nucleotides as well

short sequences

9. Methods that have been employed to map genes to chromosomes and chromosomal regions

include all of the following except:

A.  Multiplex PCR

B. Establishment of linkage of a gene locus of interest to disease traits that have already been

mapped

C. Establishment of linkage of a gene locus of interest to mapped anonymous DNA polymorphisms

D. In situ hybridization

E. Somatic cell hybridization

Q10,11 A 22 year old woman and a 24 year old man meet while attending college and decide to

marry. He is a United States citizen of Ashkenazi Jewish extraction while she is from a

Swedish religious isolate. The young man has never been tested for Tay Sachs carrier status

but knows that the disease incidence in his ethnic group is 1 in 3,600 births. The young

woman doesn't know her carrier status either, but found out from a geneticist that the disease

incidence in her subpopulation is 1 in 1,440,000.

10. Given this information, calculate the risk for this couple to have a child with Tay Sachs disease.

A. 1 in 3,600

B. 1 in 7,200

C. 1 in 36,000

D. 1 in 72,000

E. 1 in 360,000

11. The couple from the above question has a child who is healthy. They are thinking about g

another child and are again worrying about the risk of Tay Sachs disease. The father ides

to be tested and is determined to be a carrier. Given this new information, calculate risk

that they will have a child with Tay Sachs disease.

A. 1 in 1200

B. 1 in 2,400

C. 1 in 3,600

D. 1 in 4,800 2 Y

E. 1 in 12000, s

12. Which of the following designates a balanced karyotype?

A.  47,XX,+21

B.  45,X,t(21q21q)

C.  45,XX,t(21q21q) I

D.  46,XX,t(21q2lq)

E.  47,XXY,t(21q21q)

13. Mutations of autosomal genes produce disorders that may show either a dominant or progressive inheritance pattern. A dominant pattern is typically exhibited with the normal gene product:

A.  Forms multimer structures in tissues

B.  Functions primarily in early embryonic development

C.  Has a limited tissue distribution

D.  Facilitates a metabolic pathway

E.  Is an enzyme cofactor

14. Which type of Turner syndrome is usually associated with the mildest features and with fertility?

A.  45,X

B.  145,X/46,XX

C.  46,X,iso (Xq)

D.  46,X,deletion (Xp)

E.  46,X,ring (X)

15. The results of a recent study reported a DNA polymorphism linked to a debilitating dominant

disease with an adult age of onset. The data revealed a LOD (log of the odds) score =1.0 at θ=

= 0.01. What conclusion would you draw?

A.  The DNA marker maybe a good presymptomatic or prenatal diagnostic tool

B.  The study identified the site of the mutation causing the disease

C.  Families with the disease would likely benefit from this knowledge

D.  The LOD score was too low to be significant

E.  The recombination fraction (θ) is too low to support linkage

16. Multifactorial inheritance refers to:

A.  Traits that can not be measured quantitatively

B.  Traits determined by the interaction of gene ' environmental fact

C.  Traits with multiple manifestations

D.  The inheritance of birth defect syndromes

E.  Traits in which the risk for affected siblings approaches 50%

17. Duchenne and Becker refer to two distinct forms of muscular dystrophy that have been mapped

to the same (dystrophin) gene locus on the X chromosomes. They should therefore be

considered:

A.  Disomic disorders

B.  Pleiotrophic disorders

C.  Allelic disorders

D.  Closely linked disorders

E.  Reciprocally expressed disorders

18. If one of the X chromosomes is normally inactivated, why do girls with Turner syndrome knave

abnormalities?

A.  The inactivation often extends to an autosome

B.  The inactivation often extends to portions of the active X chromosome

C.  The nucleolar organizer function of the inactive X chromosome is disturbed

D.  They are monosomic for parts of the X chromosome that are not inactivated

E.  X inactivation only occurs in germ cells

19. Tumor-suppressor genes are:

A.  Genes sequentially expressed by many colonic tumors

B.  Genes transfected from certain tumor inducing viruses

C.  Genes involved in regulating the normal cell cycle

D.  Genes expressed by antitumor lymphocytes

E.  Genes duplicated in certain premalignant conditions

20. Conversion of type I procollagen to type I collagen is essential for normal connective tissue

integrity. Failure results in the Ehlers Danlos syndrome type VU, which is characterized by

severely loose joints and blood vessel fragility. In some cases it results from a point mutation

of the alpha 2 chain of type I collagen that destroys the cleavage site for procollagen peptidase,

the enzyme responsible for the conversion. In other cases it is caused by mutations of the

procollagen peptidase gene. The term that best describes this phenomenon is:

A.  Interallelic variabilty

B.  Functional complementarity

C.  Uniparental disomy

D.  Locus heterogeneity

E.  P Allelic heterogeneity

21. All of the following chromosomal syndromes show an increase in frequency with advanced maternal age except:

A.  Trisomy 21

B.  Trisomy 18

C.  Trisomy 13

D.  Klinefelter syndrome

E.  Turner syndrome

22. All of the following are aneuploid conditions except:

A.  Down syndrome

B.  Edwards syndrome

C.  Turner syndrome

D.  Klinefelter syndrome

E.  Triploidy syndrome

23. Chromosomal band differentiation as seen in G-banding, Q-banding and R-banding is primarily a function of:

A.  histone content

B.  differential adenine-thyminelguanine-cytosine distribution

C.  chromosomal scaffold structure

D.  nucleosome structure

E.  cell cycle duration

24. An infant is born with lowset ears, bilateral simian creases and very small toenails, 3 minor

anomalies. Which of the answers below best applies to this case?

A. Chromosome analysis, serum amino acids and urine organic acids should be done

immediately to rule out a metabolic disorder

B. A major anomaly, such as a congenital heart defect or cystic kidneys, should be

suspected

C. Nothing is wrong with the infant since any one of these anomalies may occur in

normal individuals

D. A magnetic resonance Image (extremely high resolution radiographic technique) of the brain should be done since CNS abnormalities usually accompany lowest ears.

E. None of the above

Q25, 26. A 6’2” father and 5'7" mother had a son with achondroplasia, a well characterized

autosomal dominant dwarfing condition After divorce the wife remarried. She and the new

husband (5' 10" tall) had another child with achondroplasia. Careful examination revealed

that both children had typical achondroplasia and no evidence of the condition in the mother.

25. What is the most likely explanation for the recurrence?

A.  Uniparental heterodisomy for the achondroplasia mutation

B.  Uniparental isodisomy for the achondroplasia mutation

C.  Gonadal mosaicism for the achondroplasia mutation

D.  Permutation of the achondroplasia mutation in the first child and conversion to the complete

mutation in the second child

E.  Instability of the mother's DNA leading to two separate mutations

26. The risk for the affected daughter to have a child with achondroplasia is

A.  Negligible uniparental isodisomy can not be transmitted through two generations

B.  Negligible, uniparental heterodisomy can not be transmitted through two generations

C.  5-10%, she may also have gonadal mosaicism

D.  100% conversion of a premutation to a mutation further increases the risk for transmission

of a heterozygous mutation

E.  50%, she has an autosomal dominant disorder


ANSWERS:

1.  E

2.  A

3.  E

4.  E

5.  C

6.  E

7.  D

8.  D

9.  C

10.  D

11.  B

12.  C

13.  A

14.  B

15.  D

16.  B

17.  C

18.  D

19.  C

20.  D

21.  E

22.  E

23.  B

24.  B

25.  C

26.  E