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(Adapted from


Formative Evaluation I (Embryology and Genetics 2010)
1. A disorder causing muscle weakness and epilepsy afflicts several members of the pedigree
below. What is the MOST LIKELY mode of inheritance?


non-genetic; environmental causes are most likely
X-linked recessive
autosomal recessive
mitochodrial (maternal inheritance)
autosomal dominant

2. A young woman of northern European descent is the single parent of a child with autosomal
recessive cystic fibrosis. She marries her first cousin and becomes pregnant. What is the
probability that her child will have cystic fibrosis?


3. The family below is segregating the mutant allele for disease X, a very rare genetic disorder
inherited in an autosomal recessive pattern, with 100% penetrance. II-2's first wife delivers an
affected child, but dies in childbirth. II-2 later marries his first wife's half-sister (II-3), and she
becomes pregnant. What is the chance that this child will be affected?


mutant allele frequency, squared (q2)

4. Choose one of the following terms that best matches each clinical vignette. Each term may be
used once, more than once, or not at all.
A. Variable expressivity
B. Anticipation
C. Incomplete penetrance
D. Allelic heterogeneity
E. Locus heterogeneity

A 24-year-old woman with myotonic
dystrophy has significant muscle
weakness and wasting. She has a oneyear-old son with very poor muscle tone
and severe weakness and significant
developmental delay. Her affected 55year-old father has cataracts but no
muscle weakness.






A man and a woman, each of whom has
autosomal recessive congenital
deafness, have four biological children,
each of whom has normal hearing.






A B C D E • Molecular analysis of the ornithine transcarbamylase (OTC) gene is carried out on two unrelated boys with X-linked OTC deficiency. His 19-year-old son has cafe-au-lait spots. His 43-year-old sister has cafe-au-lait spots and Lisch nodules of the iris. What is the chance that the fetus (IV-1) is affected with this disease? A B C D E 1/4 1/2 1/9 2/9 4/9 . A B C D E 5. the other has a missense mutation in an exon toward the 3' end of the gene.• A 40-year-old man with neurofibromatosis (NF1) has a plexiform neurofibroma of his leg that has caused significant disfigurement. One is found to have a large deletion in the 5' end of the gene. and scoliosis (curvature of the spine). a dozen cutaneous neurofibromas. The disease is present and recognizable at birth and does not decrease fitness. Assume no locus heterogeneity. but no neurofibromas. and hundreds of cutaneous neurofibromas. The family below is segregating a very rare autosomal recessive disease with 100% penetrance.

Below is a portion of a large pedigree segregating for a particular coagulation disorder. but they result from mutations in different genes on the X chromosome. This is an example of: A Double heterozygosity Compound heterozygosity B C Locus heterogeneity Allelic heterogeneity D Variable expressivity E . What mode of inheritance is demonstrated? A B C D E autosomal dominant X-linked dominant mitochondrial inheritance autosomal recessive X-linked recessive 7. Hemophilia A and hemophilia B have nearly identical phenotypes.6.

Myotonic dystrophy may show increasing severity and earlier age of onset in successive generations.  8. What is the most likely pattern of inheritance in this pedigree? A B C D E Mitochondrial X-linked dominant Autosomal dominant Autosomal recessive X-linked recessive 9. This phenomenon is known as: A Variable expressivity Locus heterogeneity B Compound heterozygosity C D Incomplete penetrance Anticipation E . What is the most likely pattern of inheritance in this pedigree? A B C D E Autosomal recessive X-linked dominant Autosomal dominant X-linked recessive Mitochondrial 10.

Ean X-linked recessive disease.11. C always caused by the same point mutation in the beta-globin gene.The "triplet repeat" in Huntington Disease refers to: An amino acid repeat consisting of: C-A-G A A nucleic acid repeat consisting of: G-A-T B An amino acid repeat consisting of: Gly-X-Y C A nucleic acid repeat consisting of: C-A-G D A nucleic acid repeat consisting of: T-A-G E .Sickle cell anemia is: A caused by mutations in either the alpha-globin gene or the beta-globin gene. B rarely due to the same mutation in unrelated individuals. 13. an autosomal recessive condition. What is the best estimate that individual I-3 is a carrier of cystic fibrosis? A B C D E 1/4 1/3 1/2 2/3 3/4 12. The pedigree below is from a family with cystic fibrosis. D an autosomal dominant disease.

Which bands would be seen in a Southern blot of DNA from normal subjects digested with EcoRI and hybridized with Probe A? A 4 kb band. The dark box represents the location of a particular DNA probe 'A'. 3kb. '*' represents polymorphic EcoRI sites. 3kb. 6kb E None of the above . RNA contains the base adenine (A) in place of guanine (G). A True B False 15. 4kb. The DNA shown below is from the 3' end of the -globin gene. 4kb. 2kb.e. 6 kb band.14. 'E' represents invariant EcoRI restriction sites. 3kb. 5kb. 6kb D 2kb. size of bands) seen on a Southern blot probed with 'A'? A 1kb. What are all the possible alleles (i. A particular RFLP is diagrammed below. which is mutated in sickle cell anemia (autosomal recessive). and 10 kb band B 6 kb band only C 6 kb band and 10 kb band D 4 kb band and 10 kb band E 4 kb band only 16. 6kb C 3kb. 6kb B 1kb. 4kb.

True or False: If disease X is linked to marker locus Y. The concept that genetic counseling must be nondirective arises directly from respect for which of the following principles of medical ethics? A Justice B Paternalism C Autonomy D Beneficence E None of the above . A True B False 20. and it is useful for linkage analysis in HD families. The G8 RFLP marker is closely linked to the Huntington disease (HD) locus. True or False: The base changes responsible for the G8 polymorphism are also responsible for HD. then there must be an association between disease X and a particular allele of marker locus Y. A True B False 19.17. The "triplet repeat" in Huntington Disease refers to: A A nucleic acid repeat consisting of: C-A-G B A nucleic acid repeat consisting of: G-A-T C An amino acid repeat consisting of: C-A-G D An amino acid repeat consisting of: Gly-X-Y E A nucleic acid repeat consisting of: T-A-G 18.

D All of the above E A and C only 22. Note that the 6kb band on the daughter (II-2) and the 4kb band on the mother (I-2) are of double intensity. Below is a family with a normal son. The results are shown below the pedigree. 8kb. She begs you not to tell the test result to her boyfriend of 4 years. C You see a patient in the psychiatry outpatient clinic who tells you he has recurring thoughts of murdering his wife. Confidentially in the physician-patient relationship should be broken in which of the following clinical scenarios? A A young woman has just tested positive for HIV. 6kb. and a daughter with trisomy 13. and he is now devising a realistic plan to do so. DNA samples from all four individuals were analyzed for an RFLP on chromosome 13.21. and 4kb. B Your 23 year-old patient is starting a new job and her employer requests the results of her genetic test for expansion of triplet repeats in the Huntington Disease gene. Based on these data. in which meiotic division did the non-disjunction event occur? A B C D E Paternal meiosis I Paternal meiosis II Maternal meiosis I Maternal meiosis II Maternal meiosis I or maternal meiosis II . This RFLP has alleles of 10kb.

C PWS results from an anomaly of X-chromosome inactivation.  23. Which of the following is least likely to be found in a live-born infant? 46. XY with a point mutation in the HMG domain of the SRY gene E 46. D The maternal copy of the gene(s) responsible for PWS exerts a dominant negative effect of the paternal allele. XY with an interstitial deletion of Yp involving the SRY gene B 46. XY with X-linked androgen receptor deficiency . XX C 45. XX. E The paternal copy of the gene(s) responsible for PWS is imprinted and is not expressed. X D 46. X B 47. B The maternal copy of the gene(s) responsible for Angelman syndrome (AS) is imprinted and is not expressed. XX. XY A 45. XXX E 25. 24. In which of the following phenotypic females does a testis develop? A 46. +21 C 47. All of the following karyotypes are found in spontaneous abortuses. The reason for this is: A The maternal copy of the gene(s) responsible for PWS is imprinted and is not expressed. Prader-Willi syndrome (PWS) can result from either an interstitial deletion involving the paternal copy of chromosome subregion 15q1-q13 or from maternal uniparental disomy of chromosome 15. +16 D 69.

21q) C 45. XX 46.  26. Which of the following individuals has the greatest risk of also being affected? A B C D III-1 III-2 III-3 IV-2 27. -14. -14. +t(14q. Below is a pedigree of a family with Fragile X Mental Retardation (FMR). XY.21q) D 45. -21. XY. +t(14q. +t(14q. which of the following is LEAST likely? A 46. Filled symbols represent individuals with mental retardation. -21. +t(14q. Among their liveborn offsping. XX. -14. XX.21q) B 46. -14. XY.21q) karyotype has a karyotypically normal husband. A phenotypically normal woman with a 45.21q) E . +t(14q. -21. -21.

2 C 1. (Letters refer to polymorphic loci. 1 1. Which of the following human diseases is least likely to be caused by aneuploidy? Down syndrome A Turner syndrome B Fragile X syndrome C Klinefelter syndrome D . 2. 2. 2 1. 2. numbers refer to alleles at that locus.XX/45. 2 2. 1 D 1. 2 1. 1 2. Nondisjunction is most likely to have occurred in: maternal meiosis I A maternal meiosis II B paternal meiosis I C paternal meiosis II D mitosis after fertilization E 30. 2 A B C D E Maternal meiosis I Maternal meiosis II Paternal meiosis I Paternal meiosis II Paternal meiosis I or II 29. A chromosomal analysis is obtained on a young woman with mild signs of Turner syndrome and reveals a 46.) In which meiotic division did nondisjunction occur? Marker Locus Father Mother child A 1. DNA analysis if 21q polymorphic markers reveals the following results. 2 B 1. 1 1. 1 1. 2 1. A karyotypically normal couple has a child with trisomy 21 Down syndrome.  28.X karyotype. 1.

For a given autosomal recessive disease. Approximately what percentage of the population has two copies of the normal allele? 2% A 19% B 90% C 95% D 98% E . filled symbols represent mentally retarded individuals. affected individuals have >230 repeats. Caucasian population. Fragile X syndrome (FraX) is an X-linked disease characterized by moderate to severe mental retardation. The molecular basis for this disease is expansion of a CGG triplet repeat in the first exon of the FMR-1 gene on the long arm of the X-chromosome. is 1/50. q.01 (where q is the allele frequency of the mutant allele).S.  31. What is the probability that III4 will be retarded because of FraX? A B C D E <1% 10% 25% 40-50% 80-100% 32. Normal individuals generally have 6-52 repeats with a mode of 30. In the pedigree. Assuming Hardy-Weinberg equilibrium for alleles at the CFTR (cystic fibrosis) locus in the U. The number of CGG repeats is shown below the symbols for individuals in generations I and II. q = 0. and given that the mutant allele frequency. what fraction of this population are carriers of a CFTR mutation? (49/50)2 A (1/50)2 B 1/50 C 1/100 D E 2/50 33.

B Association of ankylosing spondylitis with the B27 allele of the HLA-B locus. . 95% of Caucasian patients are positive for the HLA-B27 haplotype. This is evidence for: A Linkage of ankylosing spondylitis to the HLA-B locus. A True False B 36. is approximately 4%. a nonlethal autosomal recessive disorder.) A 1/1000 1/500 B 1/250 C 1/50 D 1/25 E 37. The average recurrence risk for a couple that has had a child with cleft lip.000. Which statement is a prediction of the multifactorial threshold model? A The differential risk to relatives of an affected proband increases as the disease prevalence decreases. If 1 out of every 250.000 people have Disease X. C Neither.000. 35.000 is greater than the heterozygote carrier frequency for an autosomal recessive disease with a disease frequency of 1/1. C An individual's risk is not altered by the number of affected first-degree relatives. 7% of all Caucasians are positive. Ankylosing spondylitis is a chronic inflammatory arthritis affecting the spine and sacroiliac joints. a multifactorial birth defect. The heterozygote carrier frequency (2pq) for an X-linked recessive disease with a disease frequency of 1/10. What is the recurrence risk if the couple has two affected children? 2% A B 4% C 10% 25% D 50% E 38. whereas. B Affected individuals almost always have an affected parent. D The age of onset decreases when there are affected relatives in two previous generations.34. what is the approximate carrier frequency of this disease? (Assume Hardy-Weinberg equilibrium.

40.39. Which individual's marker genotype demonstrates that the recombination has occurred? I-1 A II-2 B III-3 C III-4 D III-5 E . Which of the following observations is the strongest evidence for an important genetic component in the causation of type-1 diabetes mellitus (IDDM)? A Pancreatic B-cell autoantibodies are frequently present. The disease in this family is linked to which allele of the marker? A A B B C C D D 41. The family below is segregating an autosomal form of Ehlers-Danlos syndrome. D The concordance rate in monozygotic twins is approximately 30%. with results shown below each individual (A-D represent individual alleles for the DNA marker). Assume only one recombination event has occurred in this family between the marker locus and the disease gene mutation. E The concordance rate in monozygotic twins is five times that in dizygotic twins. Shaded individuals are affected with the disorder. C Onset of disease is usually in childhood. B Approximately 10% of affected indivifuals have an affected sibling. You type each of the family members for a polymorphic DNA linked marker.

  42. which of the following is the most likely explanation for the loss of heterozygosity in this individual? A Loss of the normal chromosome 13 B Independent second mutation C Mitotic crossover D Loss of the normal chromosome 13 and reduplication of the mutant chromosome 13 43. C In a person heterozygous for a particular DNA polymorphism. and a normal copy from the other parent. sub-chromosomal fragments (double minutes) 44. An affected individual typically inherits a single defective copy from one parent. T = tumor cells). Familial retinoblastoma (FRB) is an autosomal dominant cancer predisposition syndrome. All of the cells from the tumor express the same G6PD allele. Based upon these data. D All cells from the tumor carry an identical rearrangement of the immunoglobin gene cluster. . Each of the following have been observed as mechanisms resulting in the activation of a proto-oncogene except: A a chromosome translocation fusing portions of the oncogene and another cellular gene B inactivation of an oncogene by telomerase activity C a point mutation altering the function of the oncogene protein product D Capture of the oncogene sequence by a retrovirus E amplification of an oncogene as small. All of the following provide supporting evidence for the clonal origin of a tumor EXCEPT: A All cells from the tumor carry the same abnormal chromosome. all tumor cells show reduction to homozygosity for the same marker allele. both normal and tumor cells were typed for three RFLP markers flanking the RB locus on chromosome 13 (N = normal cells. Below are Southern blots for an individual with FRB. B The tumor is from a female heterozygous for a G6PD polymorphism. due to a defect in the RB tumor suppressor gene.

Which of the following clinical features are characteristic of familial cancer syndromes? A Observed tumor types are rarely seen as sporadic cancers B Earlier mean age of cancer onset. compared to sporadic form of the same tumor type C Two or more independent primary tumors in a single individual D all of the above E none of the above F A&B 48. Which is NOT a typical mechanism by which a proto-oncogene is converted to an oncogene? A Complete deletion of the proto-oncogene B Amplification of the proto-oncogene C A chromosomal translocation resulting in the up-regulation of the proto-oncogene D A point mutation in the proto-oncogene . Potential mechanisms for inactivation of the other allele in a retinoblastoma tumor arising in one of these patients include: A Mitotic crossing over B loss of the normal chromosome 13 C an independent point mutation D all of the above E none of the above F A&C 46. The functions which have been identified for the proteins expressed by cellular protooncogenes include all of the following except: A enzyme involved in DNA mismatch repair B growth factor receptor C component of a signal transduction pathway D growth factor E transcription factor 47. 45.E All cells from the tumor carry exactly 46 chromosomes. Patients with familial retinoblastoma carry a germline mutation in one copy of the Rb gene.

it must be correct!" What is the chance your friend is NOT a carrier? A 2% B 10% C 17% D 49% E 83% 51. using the sis gene as a probe. and genetic testing) to determine the etiology of the infant's problems. spend time with. A couple in their 30's who have two healthy children now have a pregnancy that results in the birth of a stillborn girl with multiple congenital anomalies. With that level of sensitivity.  49. E Recommendation for the mother to have an immediate tubal ligation (sterilization procedure) during this hospitalization to avoid a recurrence of the same problem. but he says. Your best friend comes to you very upset--he has just taken a screening test for this disease and gotten a positive result. B Options regarding funeral. A True B False 50. memorial. especially given they already have two healthy children. Consider an autosomal recessive disease with an incidence of 1/10. autopsy. and hold their stillborn infant. The Clinic said this test has 98% sensitivity and 90% specificity. C Further evaluation of the infant (including physical examination. . and/or burial services.000 people in Ann Arbor). Which of the following would be least appropriate to talk to the couple about shortly after their daughter's birth? A Available genetic counseling and social services. "Don't bother. You try to reassure him. despite having no family history of the disease. You perform a Southern blot on your own DNA. D Opportunities to see. and find several hybridizing bands. True or False: This result demonstrates chronic infection of your blood cells with the SSV virus. The transforming oncogene of the Simian Sarcoma Virus (SSV) is the sis gene.000 in the general population (assume 100. He is convinced he is a carrier.

Both of their parents are deceased.  52. Her brother died at age eight of documented cystic fibrosis. C when a first or second degree relative is known to be affected. E Only A and C above. 53. Which is true of newborn screening tests for genetic diseases? Newborns are typically screened for genetic diseases: A which are treatable and/or preventable. E Newborns are screened for all known genetic diseases. A 26-year-old woman of Norwegian descent seeks genetic counseling. newborn infant. otherwise completely normal. 54. D which are irreversible or untreatable disorders. This birth defect may be associated with the following: A A disruption defect related to amniotic bands. B A healthy. B which are fatal by one year of age. A child is born with a cleft lip and palate. C A chromosome disorder such as trisomy 13. The woman undergoes DNA testing for 70 CF mutations which collectively detects approximately 90% of CF carriers of northern European descent. D All of the above. Testing reveals that she is negative for all 70 mutations. What is the probability that she is a heterozygous carrier of CF? A 2/3 B 1/6 C 1/15 D 1/25 E < 1% .

The family below is segregating an X-linked recessive disorder with 100% penetrance. Shaded individuals are affected with the disorder. A 26-year-old male medical student who has no neurological or psychiatric problems undergoes genetic testing to determine if he has a mutation in his Huntington Disease (HD) gene. C These test results are inconclusive and therefore his 50/50 risk of inheriting the disease from his mother has not been modified by the test. it is most likely that he will never develop the disease. His test results are: HD allele 1: 17 repeats HD allele 2: 43 repeats The most accurate interpretation of this test is: A He is an asymptomatic individual who inherited an HD gene mutation and will develop symptoms of the disease if he lives long enough. D He has HD and should seriously consider another occupation as he will never be able to practice medicine competently. E He has inherited one HD gene mutation. including his mother. Several of his maternal relatives. What is the chance that the woman's next child (IV-5) is an affected son? A 1/4 B 1/8 C 1/9 D 1/18 E 1/36 . B Luckily. 56.  55. have well documented HD. Therefore he is only a gene carrier and will never develop the disease. but given that he currently has no symptoms by the age of 26. he has one normal allele.

The family below is segregating a mutation for Duchenne Muscular Dystrophy (DMD).7% D 50% E 33.3% 58. This disorder is 100% penetrant at birth. and 5% false positive rate.5% C 66. aged 1 y. have normal karyotypes.. She undergoes a carrier screening test which detects carriers with 98% sensitivity. Both III-1. Which of the following is the best estimate of her risk for being a carrier? A 100% B 97. she tests positive. and has an abnormal muscle biopsy. Individual III-1. What is the risk that III-2 is a carrier for DMD? A 0% B 25% C 50% D 75% E 100% . Filled symbols represent individuals affected with DMD. a lethal X-linked recessive disorder.57. has muscle weakness and wasting. and her sister III-2. A woman has a brother affected with a rare autosomal recessive disorder (she herself is not affected). 5 y.o..o.

True or False: Presymptomatic diagnosis for Huntington's disease requires DNA analysis of at least one affected relative. This high frequency of G6PD mutations is best explained by: (Biochemical and Molecular Genetics of Human Disease) A Genetic drift. C The mild phenotype of G6PD deficiency.  59. G6PD deficiency is common in African. EXCEPT: A Reproductive options are available B Genetic counseling is provided with the testing C The screening test has a positive predictive value of 100% D A high-risk population can be identified E The disease is severe enough to be clinically significant 62. and Asiatic populations in which malaria has been endemic. Genetic counseling includes all of the following EXCEPT: A Assessment of the occurrence or recurrence risk B Discussion of the impact of the disease on the patient and family C Discussion of available genetic testing D Recommendation of specific reproductive options E Discussion of available therapies 61. all of the following are essential. D Founder effect. Multiple different mutations have been found in different populations. B Balanced polymorphism. . E The influence of drugs that cause hemolytic anemia. To establish a successful and cost-effective screening program for detecting heterozygous carriers of an autosomal recessive disease. Mediterranean. A True B False 60.

Normal. or HbH disease. which of the following is NOT a possible genotype of their offspring? A a-/-a-/aB aa/aC aa/-D E aa/aa 65. The g (gamma) to b-globin switch is not complete until several months after birth. ---------------. C D Elevated hemoglobin A2 compensates for the missing b-globin genes.End of the test ---------------- . The child of II-2 died of hydrops fetalis. Assuming no genetic recombination. Severe b-thalassemia may not become clinically apparent until a child is several months old because: A The a-globin genes don't turn on until several months after birth. I-1 is of African descent. What are the most likely possible phenotypes of II-1? A B C D E HbH disease. B The oxygen needs of a newborn are minimal. Silent carrier. a-thalassemia trait only. a-thalassemia trait. An alpha-thal silent carrier man (aa/a-) mates with an alpha-thal trait woman (aa/--). 64. E Overexpression of z-globin (zeta) compensates for the missing b-chain. or hydrops fetalis. In the pedigree below. all individuals in generation I have a-thalassemia trait. Normal. or silent carrier. or hydrops fetalis.63.