Genetics exam

RNA contains the base adenine (A) in place of guanine (G). A False B True

A

Myotonic dystrophy may show increasing severity and earlier age of onset in successive generations. This phenomenon is known as: A Locus heterogeneity B Incomplete penetrance C Anticipation D Variable expressivity E Compound heterozygosity

C

In which of the following phenotypic females does a testis develop? A 46, XX B 45, X C 46, XY with an interstitial deletion of Yp involving the SRY gene D 46, XY with a point mutation in the HMG domain of the SRY gene E 46, XY with X-linked androgen receptor deficiency

E

Type III collagen is a homo-trimer of a1 (III) chains. If one of the two copies of the COL3A1 gene (which codes for this protein) contains a missense mutation which produces a mutated (but stable) protein, what fraction of type III collagen molecules will contain a mutant subunit and thus be abnormal? A 1/8 B 1/4 C 1/2 D 3/4 E 7/8

E

You see a previously healthy 3-day-old male infant who is very lethargic, vomiting, and had a seizure. Which of the laboratory tests would be most appropriate to obtain initially to confirm your suspicions? A just a plasma phenylalanine level B plasma phenylalanine and tyrosine levels C a 24 hour urine homogentisic acid level D ornithine transcarbamylase gene sequence E serum ammonia level

E

You would appropriately suspect a possible collagen disorder in a patient who has any of the following symptoms except: A joint hypermobility or laxity B rupture of the bowel C blue sclerae D multiple fractures E progressive neurological deterioration

E

Which karyotype would be MOST frequently seen in liveborn infants (as opposed to spontaneous abortions)? A 46,YY B 47,XX,+3 C 69,XXX D 46,XY,-11,+22 E 47,XX,+21

E (Downs)

Select the one best answer: A. Polygenic disease B. Allelic heterogeneity C. Variable expressivity D. Locus heterogeneity E. Polymorphism 1) About 10% of pheochromocytomas (a tumor of the adrenal medulla) occur in patients with familial cancer syndromes, one of which is multiple endocrine neoplasia syndrome, type II (MEN-II). In most MEN-II families, there are germline mutations in the RET gene, located on chromosome 10. Most commonly, these mutations are in one of several different codons encoding cysteines. This is an example of: A B C D E 2) MEN-II is an autosomal dominant cancer syndrome. Another autosomal dominant cancer syndrome associated with pheochromocytomas (and occasionally misdiagnosed as MEN-II) is von Hippel-Lindau disease, the gene for which is on chromosome 3. With regard to familial pheochromocytomas, these two diseases are examples of: A B C D E 3) 95% of individuals affected with MEN-II have thyroid C-cell hyperplasia and medullary thyroid carcinoma, 50% have pheochromocytoma, and about 20% have hyperparathyroidism. This is an example of: A B C D E

1. B 2. D 3. C

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 1) A 24-year-old woman with myotonic dystrophy has significant muscle weakness and wasting. She has a one-year-old son with very poor muscle tone and severe weakness and significant developmental delay. Her affected 55-year-old father has cataracts but no muscle weakness. A B C D E 2) 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 3) A 40-year-old man with neurofibromatosis (NF1) has a plexiform neurofibroma of his leg that has caused significant disfigurement, and hundreds of cutaneous neurofibromas. His 43-year-old sister has cafe-au-lait spots and Lisch nodules of the iris, but no neurofibromas. His 19-year-old son has cafe-au-lait spots, a dozen cutaneous neurofibromas, and scoliosis (curvature of the spine). A B C D E 4) Molecular analysis of the ornithine transcarbamylase (OTC) gene is carried out on two unrelated boys with X-linked OTC deficiency. One is found to have a large deletion in the 5' end of the gene; the other has a missense mutation in an exon toward the 3' end of the gene. A B C D E

1.B 2. E 3.A 4.D

All of the following provide supporting evidence for the clonal origin of a tumor EXCEPT: A All cells from the tumor carry exactly 46 chromosomes. B All cells from the tumor carry the same abnormal chromosome. C In a person heterozygous for a particular DNA polymorphism, all tumor cells show reduction to homozygosity for the same marker allele. D All cells from the tumor carry an identical rearrangement of the immunoglobin gene cluster. E The tumor is from a female heterozygous for a G6PD polymorphism. All of the cells from the tumor express the same G6PD allele.

A

An alpha-thal silent carrier man (aa/a-) mates with an alpha-thal trait woman (aa/--). Assuming no genetic recombination, which of the following is NOT a possible genotype of their offspring? A a-/a- B aa/aa C aa/a- D aa/-- E a-/--

A

Ankylosing spondylitis is a chronic inflammatory arthritis affecting the spine and sacroiliac joints. 95% of Caucasian patients are positive for the HLA-B27 haplotype; whereas, 7% of all Caucasians are positive. This is evidence for: A Association of ankylosing spondylitis with the B27 allele of the HLA-B locus. B Linkage of ankylosing spondylitis to the HLA-B locus. C Neither.

A

During normal adult life the MAJOR form of hemoglobin produced in red blood cells is: A a2b2 B a2d2 C z2e2 D a2e2 E a2g2

A

G6PD deficiency is common in African, Mediterranean, and Asiatic populations in which malaria has been endemic. Multiple different mutations have been found in different populations. This high frequency of G6PD mutations is best explained by: A Balanced polymorphism. B The influence of drugs that cause hemolytic anemia. C Genetic drift. D Founder effect. E The mild phenotype of G6PD deficiency.

A

HbH disease is rarely observed in offspring of African American couples because: A the predominant chromosome associated with a-thalassemia in African Americans is (a-). B an overabundance of a2d2 tetramers is causative of HbH disease. C a-thalassemia is only seen in Asian populations. D hemoglobin Bart's is almost always associated with the genotype (a-/a-) in African Americans. E being affected with sickle cell anemia confers relative resistance to the effects of HbH disease.

A

Hemophilia A and hemophilia B have nearly identical phenotypes, but they result from mutations in different genes on the X chromosome. This is an example of: A Locus heterogeneity B Variable expressivity C Double heterozygosity D Compound heterozygosity E Allelic heterogeneity

A

To establish a successful and cost-effective screening program for detecting heterozygous carriers of an autosomal recessive disease, all of the following are essential, EXCEPT: A The screening test has a positive predictive value of 100% B A high-risk population can be identified C Genetic counseling is provided with the testing D The disease is severe enough to be clinically significant E Reproductive options are available

A

True or False: The short arms of acrocentric chromosomes consist mainly of a satellite and a thin stalk, containing multiple copies of genes encoding ribosomal RNAs. A True B False

A

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

A

Which is least likely to result in a b0 allele for b-thalassemia? A Missense mutation early in exon 1 of the b-globin gene. B Nonsense mutation early in exon 2 of the b-globin gene. C Deletion of the entire b-globin gene. D 7 bp deletion in exon 2 of the b-globin gene. E 20 bp insertion in exon 1 of the b-globin gene.

A

Which is true of newborn screening tests for genetic diseases? Newborns are typically screened for genetic diseases: A which are treatable and/or preventable. B which are irreversible or untreatable disorders. C when a first or second degree relative is known to be affected. D which are fatal by one year of age. E Newborns are screened for all known genetic diseases.

A

Which of the following conditions should not occur in a single individual: A Both b-thalassemia and hemoglobin SC disease. B A total of 5 copies of the a-globin gene sequence (aaa/aa). C Both a-thalassemia and hemoglobin SS disease. D Both a-thalassemia and hemoglobin SC disease. E Both a-thalassemia and b-thalassemia.

A

Which would NOT be an effective way to diagnose sickle cell anemia? A Enzymatic assay for hemoglobin activity. B PCR exon 1 of the b-globin gene, followed by ASO hybridization with oligonucleotides specific for normal and betaS alleles. C Restriction digest of genomic DNA with MstII, followed by Southern blot, using a b-globin gene product. D PCR exon 1 of the b-globin gene, followed by restriction digest with MstII. E Hemoglobin electrophoresis.

A

(U) True or False: Robertsonian translocations usually involve metacentric chromosomes. A True B False

B

A 26-year-old woman of Norwegian descent seeks genetic counseling. Her brother died at age eight of documented cystic fibrosis. Both of their parents are deceased. The woman undergoes DNA testing for 70 CF mutations which collectively detects approximately 90% of CF carriers of northern European descent. 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%

B

A large percentage of individuals with a1-antitrypsin deficiency will develop chronic obstructive pulmonary disease (COPD) or emphysema. The severity of this disease will be significantly increased if the patient is: A neutropenic. B a cigarette smoker. C homozygous for null alleles of the elastase gene. D a woman. E heterozygous for the mutation, with one normal copy of the a1-antitrypsin gene.

B

A liver transplant may be effective in treating all of the following disorders except: A a-1 antitrypsin deficiency B glucose-6-phosphate dehydrogenase (G6PD) deficiency C severe familial hypercholesterolemia D ornithine transcarbamylase (OTC) deficiency

B

A woman has a brother affected with a rare autosomal recessive disorder (she herself is not affected). This disorder is 100% penetrant at birth. She undergoes a carrier screening test which detects carriers with 98% sensitivity, and 5% false positive rate; she tests positive. Which of the following is the best estimate of her risk for being a carrier? A 100% B 97.5% C 66.7% D 50% E 33.3%

B

Alkaptonuria is caused by a deficiency of: A normal colored urine B homogentisic acid oxidase C phenylalanine oxidase D homogentisic acid E phenylalanine hydroxylase

B

Both Type I and Type II osteogenesis imperfecta (OI; 'brittle bone disease') are inherited in an autosomal dominant fashion and are usually caused by mutations in the a1 (I) collagen gene. Most mutations causing the milder Type I OI are null mutations; whereas, those causing the perinatal lethal Type II OI are usually missense mutations that allow synthesis of normal amounts of the altered collagen subunit. The explanation for the paradoxically greater phenotypic severity of Type II OI is that in Type II OI: A 100% of the procollagen molecules are abnormal. B 75% of the procollagen molecules are abnormal. C 50% of the procollagen molecules are abnormal. D All of the procollagen molecules are normal, but their total quality is reduced by 50%.

B

Each RNA nucleotide contains an additional 4' hydroxyl (-OH) group not present in DNA. A True B False

B

Linkage analysis is performed in a large family with an autosomal dominant hemolytic anemia, using a polymorphic marker within the b-globin locus. The LOD score at q=0 is negative infinity. The LOD score at q=0.01 is -4.5. You conclude that the disorder in this family: A is due to a mutation in the a-globin gene B is not due to a b-globin gene mutation C is an acquired disorder, due to a somatic gene mutation D is due to a b-globin gene mutation E is due to a mutation in a gene on chromosome 11, 10 cM centromeric of b-globin

B

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. The reason for this is: A The maternal copy of the gene(s) responsible for PWS exerts a dominant negative effect of the paternal allele. B The maternal copy of the gene(s) responsible for PWS is imprinted and is not expressed. C The paternal copy of the gene(s) responsible for PWS is imprinted and is not expressed. D The maternal copy of the gene(s) responsible for Angelman syndrome (AS) is imprinted and is not expressed. E PWS results from an anomaly of X-chromosome inactivation.

B

The "triplet repeat" in Huntington Disease refers to: A An amino acid repeat consisting of: Gly-X-Y B A nucleic acid repeat consisting of: C-A-G C An amino acid repeat consisting of: C-A-G D A nucleic acid repeat consisting of: G-A-T E A nucleic acid repeat consisting of: T-A-G

B

The G8 RFLP marker is closely linked to the Huntington disease (HD) locus, and it is useful for linkage analysis in HD families. True or False: The base changes responsible for the G8 polymorphism are also responsible for HD. A True B False

B

The frequency of autosomal dominant familial hypercholesterolemia, secondary to heterozygosity for an LDL-R mutation, is approximately 1/500. A 32-year-old affected man marries a genetically unrelated 20-year-old woman. What is the probability that a child of theirs will be affected with severe familial hypercholesterolemia secondary to compound heterozygosity for LDL-R mutations? A 1/1,000,000 B 1/2,000 C 1/1,000 D 1/250 E 1/2

B

The heterozygote carrier frequency (2pq) for an X-linked recessive disease with a disease frequency of 1/10,000 is greater than the heterozygote carrier frequency for an autosomal recessive disease with a disease frequency of 1/1,000,000. A True B False

B

The transforming oncogene of the Simian Sarcoma Virus (SSV) is the sis gene. You perform a Southern blot on your own DNA, using the sis gene as a probe, and find several hybridizing bands. True or False: This result demonstrates chronic infection of your blood cells with the SSV virus. A True B False

B

True or False: If disease X is linked to marker locus Y, then there must be an association between disease X and a particular allele of marker locus Y. A True B False

B

True or False: In X chromosome inactivation, all of the X chromosome genes are inactivated. A True B False

B

True or False: Huntington's disease results from a trinucleotide repeat expansion in intron 6 of the huntingtin gene. A True B False

B

True or False: Presymptomatic diagnosis for Huntington's disease requires DNA analysis of at least one affected relative. A True B False

B

Which of the following human diseases is least likely to be caused by aneuploidy? A Down syndrome B Fragile X syndrome C Turner syndrome D Klinefelter syndrome

B

Which one of the following karyotypes is most likely to be found normal human sperm? A 22, Y B 23, X C 46, XX D 46, XY E None of the above

B

You analyze the sequence for part of the Factor VIII gene in a male patient with hemophilia A, and find a missense base change substituting a Leu for Ile at codon 904. Analysis of the Factor VIII gene of another unrelated individual identifies the exact same base change. True or False: This second individual must also have hemophilia A. A True B False

B

You are doing an emergency medicine rotation as a third year medical student. A 4 year-old boy who has just been in a car accident is rushed in because he has severe blood loss requiring transfusion. The boy's parents refuse to give consent for the transfusion because they are Jehovahs Witnesses. You go to the judge and get a court order for the transfusion citing which of the following principles of medical ethics? A Justice B Nonmaleficence C Paternalism D Confidentiality

B

"One gene, one enzyme" is a phrase describing the concept that: A functional enzymes are never made up of subunits encoded by different genes B only one copy of the gene needs to be inactive to cause severe disease due to 50% levels of enzyme activity C individual metabolic steps are controlled by individual enzymes encoded by specific genes D most metabolic disorders are X-linked recessive E alteration of genes by rare enzymes are the main cause of metabolic disease

C

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? A 1/2500 B 1/100 C 1/32 D 1/8 E 1/4

C

Genetic counseling includes all of the following EXCEPT: A Discussion of available genetic testing B Assessment of the occurrence or recurrence risk C Recommendation of specific reproductive options D Discussion of the impact of the disease on the patient and family E Discussion of available therapies

C

If 1 out of every 250,000 people have Disease X, a nonlethal autosomal recessive disorder, what is the approximate carrier frequency of this disease? (Assume Hardy-Weinberg equilibrium.) A 1/1000 B 1/500 C 1/250 D 1/50 E 1/25

C

The average recurrence risk for a couple that has had a child with cleft lip, a multifactorial birth defect, is approximately 4%. What is the recurrence risk if the couple has two affected children? A 2% B 4% C 10% D 25% E 50%

C

The concept that genetic counseling must be nondirective arises directly from respect for which of the following principles of medical ethics? A Beneficence B Paternalism C Autonomy D Justice E None of the above

C

The major abnormal form of hemoglobin that accumulates in a fetus with the severe form of a-thalassemia (hydrops fetalis) is composed of: A A tetramer of 4 a-subunits (a4) B A tetramer of 4 b-subunits (b4) C A tetramer of 4 g-subunits (g4) D A tetramer containing 2 z-subunits and 2 e-subunits (z2e2) E A tetramer containing 2 d-subunits and 2 b-subunits (d2b2)

C

To establish a successful and cost-effective screening program for detecting heterozygous carriers of an autosomal recessive disease, all of the following are essential, EXCEPT: A A high-risk population can be identified B Genetic counseling is provided with the testing C The screening test has a positive predictive value of 100% D The disease is severe enough to be clinically significant E Reproductive options are available

C

Which statement is a prediction of the multifactorial threshold model? A An individual's risk is not altered by the number of affected first-degree relatives. B Affected individuals almost always have an affected parent. C The differential risk to relatives of an affected proband increases as the disease prevalence decreases. D The age of onset decreases when there are affected relatives in two previous generations.

C

Why is b-thalassemia major usually evident only after birth? A The fetal Hb persists after birth when it should have been shut off. B The product of the b-globin pseudogene is highly expressed only after birth. C The switch from g-gene to b-gene expression occurs around the time of birth. D The Hb subunits encoded by the a cluster (which has two copies of the a-globin gene) are sufficient until after birth. E The mother's normal red blood cells provide oxygen to the fetus in utero.

C

A phenotypically normal woman with a 45, XX, -14, -21, +t(14q, 21q) karyotype has a karyotypically normal (46, XY) husband. Among their liveborn offspring, the most likely karyotypes are 46, XY and 46, XX. Which of the following karyotypes is the next most likely among liveborn offspring? A 47, XY, +21 B 46, XY, -14, +t(14q, 21q) C 46, XY, -21, +t(14q, 21q) D 45, XY, -14, -21, +t(14q, 21q) E 45, XY, -14, -21, +16

D

A young woman of northern European descent is the single parent of a child with autosomal recessive cystic fibrosis (CF). She marries a genetically unrelated man of northern European descent and wishes to have more children. What is the risk that he is a carrier of CF? Assume the frequency of CF is 1/2500 in this population. A 1/2500 B 1/1250 C 1/50 D 1/25 E 1/4

D

All of the following karyotypes are found in spontaneous abortuses. Which of the following is least likely to be found in a live-born infant? A 46, XY B 45, X C 47, XX, +21 D 47, XX, +16 E 69, XXX

D

Approximately what percentage of all pregnancies result in the birth of a child with a significant genetic disease or birth defect that can cause crippling, mental retardation, or early death? A 0% B 0.01% C 0.1% D 3% E 25%

D

Each of the following have been observed as mechanisms resulting in the activation of a proto-oncogene except: A Capture of the oncogene sequence by a retrovirus B amplification of an oncogene as small, sub-chromosomal fragments (double minutes) C a point mutation altering the function of the oncogene protein product D inactivation of an oncogene by telomerase activity E a chromosome translocation fusing portions of the oncogene and another cellular gene

D

Patients with familial retinoblastoma carry a germline mutation in one copy of the Rb gene. Potential mechanisms for inactivation of the other allele in a retinoblastoma tumor arising in one of these patients include: A an independent point mutation B Mitotic crossing over C loss of the normal chromosome 13 D all of the above E none of the above F A & C

D

Severe b-thalassemia may not become clinically apparent until a child is several months old because: A The oxygen needs of a newborn are minimal. B The a-globin genes don't turn on until several months after birth. C Overexpression of z-globin (zeta) compensates for the missing b-chain. D The g (gamma) to b-globin switch is not complete until several months after birth. E Elevated hemoglobin A2 compensates for the missing b-globin genes.

D

The worldwide distribution of b-thalassemia, sickle cell anemia, and glucose-6-phosphate dehydrogenase (G6PD) deficiency coincides with that of: A influenza. B lactase persistence. C cholera. D malaria. E multiple sclerosis.

D

Unequal crossing over between two Alu repeats can lead to an LDL receptor gene with an internal deletion or duplication. Based on this information, which of the following must be true? A The LDL receptor gene does not contain Alu repeat sequences. B The genome contains only one copy of the Alu repeat sequence. C The LDL receptor gene contains one and only one Alu repeat sequence. D The LDL receptor gene contains at least two Alu repeat sequences. E The LDL receptor gene is an Alu repeat sequence.

D

Which of the following would NOT benefit a patient with b-thalassemia major? A Increasing fetal Hb production. B Transfusion and iron chelation therapy. C Decreasing a-globin production. D Increasing a-globin production. E Increasing b-globin production.

D

A 42-year-old woman and her 36-year-old biological brother have 10-15% of a-1 antitrypsin activity. She is healthy, but her brother has bad lung disease. The variability in their health is most likely: A because she has two X chromosomes B caused by different allelic variants of the disease C secondary to having different prenatal (in-utero) environments D caused by genetic heterogeneity E due to having different environmental exposures over the past 20 years

E

A chromosomal analysis is obtained on a young woman with mild signs of Turner syndrome and reveals a 46,XX/45,X karyotype. Nondisjunction is most likely to have occurred in: A maternal meiosis I B maternal meiosis II C paternal meiosis I D paternal meiosis II E mitosis after fertilization

E

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. Which of the following would be least appropriate to talk to the couple about shortly after their daughter's birth? A Further evaluation of the infant (including physical examination, autopsy, and genetic testing) to determine the etiology of the infant's problems. B Opportunities to see, spend time with, and hold their stillborn infant. C Available genetic counseling and social services. D Options regarding funeral, memorial, and/or burial services. E Recommendation for the mother to have an immediate tubal ligation (sterilization procedure) during this hospitalization to avoid a recurrence of the same problem, especially given they already have two healthy children.

E

A nonsense mutation in exon 14, resulting in failure of the LDL receptor to reach the cell surface, is found in individuals affected with familial hypercholesterolemia in multiple Lebanese Christian families. Which is the most likely to explain the high frequency of the mutation in this population? A Lebanese eat a diet high in animal fat. B The mutation has no detrimental effect, and therefore is not selected against. C Family size is large. D Homozygotes enjoy a survival advantage. E Founder effect.

E

Assuming Hardy-Weinberg equilibrium for alleles at the CFTR (cystic fibrosis) locus in the U.S. Caucasian population, and given that the mutant allele frequency, q, is 1/50, what fraction of this population are carriers of a CFTR mutation? A 1/100 B (1/50)2 C 1/50 D (49/50)2 E 2/50

E

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. She begs you not to tell the test result to her boyfriend of 4 years. 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. C You see a patient in the psychiatry outpatient clinic who tells you he has recurring thoughts of murdering his wife, and he is now devising a realistic plan to do so. D All of the above E A and C only

E

Consider an autosomal recessive disease with an incidence of 1/10,000 in the general population (assume 100,000 people in Ann Arbor). Your best friend comes to you very upset--he has just taken a screening test for this disease and gotten a positive result. He is convinced he is a carrier, despite having no family history of the disease. You try to reassure him, but he says, "Don't bother. The Clinic said this test has 98% sensitivity and 90% specificity. With that level of sensitivity, it must be correct!" What is the chance your friend is NOT a carrier? A 2% B 10% C 17% D 49% E 83%

E

Despite the large number of unique mutations described in the LDL-R gene that cause familial hypercholesterolemia, certain mutations are found in high frequency in specific populations, e.g., the 9.5 kb 3' deletion is found in 35% of Finnish patients. This is an example of: A Allelic heterogeneity B Balanced polymorphism C Variable expressivity D Locus heterogeneity E Founder effect

E

Each normal polypeptide chain that makes up collagen is generally characterized by: A back to back ALU repeats B triplet repeats of the nucleic acid sequence: C-A-G C triplet repeats of the nucleic acid sequence: G-X-Y D triplet repeats of the amino acid sequence: Cys-X-Y E triplet repeats of the amino acid sequence: Gly-X-Y

E

For a given autosomal recessive disease, q = 0.01 (where q is the allele frequency of the mutant allele). Approximately what percentage of the population has two copies of the normal allele? A 2% B 19% C 90% D 95% E 98%

E

Hemoglobin H disease is rarely seen in African Americans because: A Sickle cell anemia protects against hemoglobin H disease. B a-thalassemia trait is very rare among African Americans. C a-thalassemia among African Americans is usually due to a nonsense mutation in the a-globin gene. D The (a-/) a-globin allele is very rare among African Americans. E The (--/) a-globin allele is very rare among African Americans.

E

Men with an A to G substitution at position 376 in exon V of their glucose-6-phosphate dehydrogenase gene causing a substitution of aspartic acid for asparagine have the type A variant of G6PD and: A will develop hemolytic anemia B have 10% of G6PD activity C will pass this on to their sons D should avoid fava beans and certain drugs E have normal or full G6PD activity

E

Patients with hemoglobin SC disease: A Could not have a child with sickle cell disease. B Never experience sickle cell crises. C Exhibit an excess of embryonic z-chains in their adult red blood cells. D Frequently die in utero from complications of the hemoglobinopathy. E Have a different mutation in each copy of their b-globin gene, though both are in the same codon.

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. B Approximately 10% of affected indivifuals have an affected sibling. C Onset of disease is usually in childhood. D The concordance rate in monozygotic twins is approximately 30%. E The concordance rate in monozygotic twins is five times that in dizygotic twins.

E

Which of the following clinical features are characteristic of familial cancer syndromes? A Two or more independent primary tumors in a single individual B Observed tumor types are rarely seen as sporadic cancers C Earlier mean age of cancer onset, compared to sporadic form of the same tumor type D all of the above E none of the above F A & B

F

A, B, C, and D are defined in the table below. For each question, match the term with its correct definition. Affected & positive: A Unaffected & Positive: B Affected and negative: C Unaffected and negative: D A. D/(B + D) B. A/(A + C) C. C/(C + D) D. B/(B + D) E. B/(A + B) Specificity A B C D E Sensitivity A B C D E False positive rate A B C D E False negative rate A B C D E

Specificity: A Sensitivity: B False positive: E False negative: C