TEST BANK for Medical Genetics 5th Edition by Jorde, Carey, Bamshad by ACADEMIAMILL

Medical Genetics 5th Edition Jorde Test Bank Jorde: Medical Genetics, 5th Edition Chapter 1: Background and History Sample Problems & Essay Questions Question 1: Your class, which has 100 individuals, has been typed for a locus that has three possible alleles, labeled 1, 2, and 3. The genotypes and their counts are: 1,1 10 1,2 5 1,3 15 2,2 20 2,3 20 3,3 30 Based on these genotype counts, which is the gene frequency of allele 1? Answer: 20+5+15 200

40 200

0.2

Question 2: If an X-linked recessive disorder affects approximately 1/1,000,000 females (all homozygotes) in a population, what is the expected frequency of affected males in the population? Answer: q= √(1/1,000,000) = 1/1,000 Question 3: Two individuals who both have achondroplasia (autosomal dominant disorder) mate. What is the occurrence risk for this disorder in their offspring? Answer: 0.75 Question 4: Suppose that you have done a carrier test for PKU (autosomal recessive disorder) in a population, and you discover that the heterozygote carrier frequency is 1/500. Based on this information, what proportion of the population will be affected with PKU? (Note: your answer does not have to be exact.). Answer: 2pq=1/500 2q=1/500 q=1/1000 q2=1/1,000,000 Question 5: A woman with an X-linked dominant disorder mates with a phenotypically normal male. On average, what proportion of this couple's daughters will be affected with the disorder? Answer: 0.50 Question 6: A woman who is a heterozygous carrier of an X-linked recessive disease gene mates with a phenotypically normal male. The disease gene has a penetrance of

Sample Problems & Essay Questions

80%. On average, what proportion of this couple's sons will be affected with the disorder? Answer: 0.8 x 0.5 = 0.4 Question 7: In the accompanying pedigree, a man is affected with tyrosinase-negative oculocutaneous albinism (autosomal recessive). Based on this information alone, what is the probability that his grandson (labeled A) and his great-granddaughter (labeled B) are both heterozygous carriers of the albinism gene?

Answer: 1/8 Question 8: A woman has an autosomal dominant form of postaxial polydactyly. N ine RS I yGotTher B.C M Assuming that you have not examU d anN famOily members to determine whether they have postaxial polydactyly, what is the probability that her second cousin (labeled A in the pedigree) is also affected with this fully penetrant disorder?

Answer: (1/2)^6 + (1/2)^6 = 1/32 Question 9: Discuss the concept of pleiotropy. Use at least two disease examples to illustrate the concept. (This answer should require no more than about five sentences.)

Sample Problems & Essay Questions

Answer: Pleiotropy describes a common situation in which a single gene defect produces multiple phenotypic problems. There are many pleiotropic genes, some examples of which are: Marfan syndrome: fibrillin mutation causing ocular, skeletal, and cardiovascular problems (especially mitral valve prolapse and dilation of ascending aorta). Cystic fibrosis: mutations in the CFTR gene reduce chloride ion transport across the apical surface of some epithelial cells. This leads to elevated sweat chloride, pancreatic insufficiency (in most cases), and production of thick mucus in the airway. Neurofibromatosis type 1: mutations in the NF1 gene (encoding neurofibromin) can cause Lisch nodules, neurofibromas, skeletal defects (e.g., pseudarthrosis, sphenoid wing dysplasia), malignancies, hypertension, cafe-au-lait spots. Osteogenesis imperfecta: Mutations in type 1 procollagen lead to brittle bones, hearing loss, blue sclerae (in some cases). (Down syndrome was also accepted as an answer, although Down syndrome is not a single-gene disorder.) Question 10: Hereditary diseases often present with no previous family history of the disorder. Briefly describe three N situ atio nsNinGwh UR SI TBic.hCyou OMwould be most likely to observe a genetic disorder for which there is no previous family history of the disease phenotype (three brief sentences should be sufficient). Answer: Some possibilities: Autosomal recessive diseases usually have no previous history (consanguinity may be present, but usually is not for relatively common autosomal recessive disorders). New mutation transmitted by one of the parents. Germline mosaicism in one of the parents. Most chromosome abnormalities (aneuploidies, translocations, deletions, duplications) have no previous family history. Reduced penetrance can produce no previous history, although the penetrance would have to be very low. Anticipation is a possibility, although all diseases in which anticipation has been observed are dominant and thus they usually do have a previous family history.

Sample Problems & Essay Questions Question 11: Match the pedigree with the most likely mode of inheritance. Note that complicating factors, such as reduced penetrance, may be present. Assume that the gene frequency of the disorder in the general population is very low. These answers may be used more than once.

a. autosomal dominant b. autosomal recessive c. X-linked recessive d. X-linked dominant e. mitochondrial Answer: d Question 12: Match the pedigree with the most likely mode of inheritance. Note that complicating factors, such as reduced penetrance, may be present. Assume that the gene frequency of the disorder in the general population is very low. These answers may be used more than once.

a. autosomal dominant b. autosomal recessive c. X-linked recessive

Sample Problems & Essay Questions d. X-linked dominant e. mitochondrial Answer: a

Jorde: Medical Genetics, 5th Edition Chapter 2: Basic Cell Biology: Structure and Function of Genes and Chromosomes Sample Problems & Essay Questions Question 1: In some African populations, the prevalence of sickle cell disease, an autosomal recessive condition, is 1/100. Based on this value, what proportion of the population would be heterozygous carriers of the sickle cell disease gene? Answer: q = 0.1 p = 0.9 2pq = 0.18 Question 2: If an X-linked dominant disorder affects 1/100 males in a population, what is the gene frequency for the disorder in the population? Answer: 0.01 Question 3: In the population in question 2 (an X-linked dominant disorder affects 1/100 males in a population), what proportion of females would be affected with the X-linked dominant disorder? Answer: q^2 + 2pq = ~2q = 0.02 = 1/50 Question 4: A man who is affecNteUdRwSitI hN heGmToB ph.ilC iaOAM(X-linked recessive) mates with a woman who is a heterozygous carrier of this disorder. What proportion of this couple's daughters will be affected, and what proportion of the daughters will be carriers? Answer: 0.50; 0.50 Question 5: A man who has Neurofibromatosis type 1 (autosomal dominant) marries a phenotypically normal woman. If they have five children, what is the probability that none of the children will be affected with this disorder? What is the probability that all of the children will be affected? Answer: (1/2)^5 = 1/32 1/32; 1/32 Question 6: You have ascertained a fully penetrant autosomal dominant disease condition in three offspring of a couple with no family history of the disorder. What is the most likely explanation for the pedigree shown here?

Sample Problems & Essay Questions

Answer: Germline mosaicism Question 7: In the accompanying pedigree, a man is a known heterozygous carrier for an autosomal recessive disease gene that has 60% penetrance in affected homozygotes. If he marries his second cousin, what is the probability that their offspring will be affected with the disorder (i.e., that they will manifest the disease phenotype)?

Answer: 1/32 x 1/4 x 0.6 = 1/128 x 0.6 = 0.0046875 Question 8: Name at least two features you would use to distinguish an autosomal dominant pedigree from an X-linked recessive pedigree. Answer: Autosomal dominant: Father-son transmission, approximately equal proportions of males and females, skipped generations rare under full penetrance X-linked recessive: No father-son transmission, males are more often affected than females, skipped generations through unaffected females is common Question 9: It has been observed that missense mutations in the fibrillin-1 gene on chromosome 15 often produce more severe presentations of Marfan syndrome than do nonsense mutations in the same gene. Explain this (4-5 sentences should suffice). Answer: The fibrillin-1 gene product forms a subunit of a multimeric protein. An individual with Marfan syndrome is usually a heterozygote and thus has one normal copy of fibrillin-1 and one mutated copy. A nonsense mutation results in premature truncation of the translated fibrillin subunit. Typically this subunit cannot bind with other subunits, so the abnormal fibrillin produced by the mutated gene does not affect the normal fibrillin produced by the normal gene copy. as a result, the individual has about 50% of the

Sample Problems & Essay Questions

normal level of fibrillin-1. The abnormal fibrillin-1 resulting from a missense mutation may bind with the normal fibrillin gene product, damaging it as well. This "dominant negative" effect results in a more severe expression of the disease phenotype. Question 10: Explain the relationship between trinucleotide repeats and anticipation. Use at least two disease examples to illustrate your points. Answer: Anticipation describes earlier age of onset and more severe expression of a disease phenotype in more recent generations of a pedigree. In some cases, such as Fragile X syndrome, Huntington disease, myotonic dystrophy, and spinocerebellar ataxia type 1, anticipation can be explained by the tendency of trinucleotide repeat units to expand from generation to generation. Sometimes this expansion may be influenced by the parent's gender (e.g., expansion of the Huntington disease trinucleotide repeat is more likely if the transmitting parent is male, while expansion of the myotonic dystrophy and Fragile X repeats are more likely if the transmitting parent is female). Question 11: Match the pedigree with the most likely mode of inheritance. Note that complicating factors, such as reduced penetrance, may be present. Assume that the gene frequency of the disorder in the general population is very low. These answers may be used more than once.

a. autosomal dominant b. autosomal recessive c. X-linked recessive d. X-linked dominant e. mitochondrial Answer: e Feedback: (all children of affected females have the disease) Question 12: Match the pedigree with the most likely mode of inheritance. Note that complicating factors, such as reduced penetrance, may be present. Assume that the gene frequency of the disorder in the general population is very low. These answers may be used more than once.

Sample Problems & Essay Questions

a. autosomal dominant b. autosomal recessive c. X-linked recessive d. X-linked dominant e. mitochondrial Answer: a Feedback: (no skipped generations, passed from father to son)

Jorde: Medical Genetics, 5th Edition Chapter 3: Genetic Variation: Its Origin and Detection Sample Problems & Essay Questions Question 1: The H-Y antigen is encoded by a gene on the human Y chromosome. Suppose that a variant allele at the H-Y locus is found in one in 1,000 males in a population. What is the gene frequency of this allele in the male population? Answer: 1/1000 Question 2: Continuing question 1, what is the gene frequency of this allele in the female population? Answer: 0 Question 3: Hemochromatosis is a common autosomal recessive disorder of iron absorption. The gene frequency is approximately 0.05 (1/20) in some Northern European populations. If the penetrance of the disease-causing genotype is 0.5 in males and 0.2 in females, what is the expected incidence of the disease phenotype in the male and female populations? Answer: Males: (1/20)^2 x 0.5 N =U 1/R 80S0INGTB.COM Females: (1/20)^2 x 0.2 = 1/2000 Question 4: List at least three explanations for the pedigree shown below for a Mendelian (single-gene) disease (for each explanation, a 2-3 word phrase is sufficient).

Answer: New Mutation Incomplete penetrance Autosomal recessive X-linked recessive

Question 5: A 25-year-old woman has had three children with Down syndrome. Give two possible explanations (for each explanation, a 2-3 word phrase is sufficient). Answer: Germline mosaicism, Robertsonian translocation, Reciprocal translocation involving distal 1/3 of 21q.

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Question 6: A man who is a known heterozygous carrier of a cystic fibrosis mutation marries his half first cousin (see pedigree). What is the probability that this couple will produce a child with cystic fibrosis (autosomal recessive disorder)?

Answer: (1/2)^4 x 1/4 = 1/64 Question 7: A woman who has normal skin pigmentation has two sisters with oculocutaneous albinism, a fully penetrant autosomal recessive disease. What is the probability that this woman is a heterozygous carrier of the disease gene? Answer: 2/3 Question 8: Consider a woman who is a known heterozygous carrier of a mutation that causes PKU (autosomal recessive). What is the probability that her two grandchildren (shown in the pedigree as individuals A and B) are both heterozygous carriers of this PKU-causing allele?

Answer: 1/2)^4 = 1/16 Question 9: Explain the difference between variable expression and incomplete penetrance. Use at least two disease examples to illustrate your discussion (4-5 sentences should be sufficient). Answer: (NOTE: because I have included multiple examples, these answers are a little longer than I expect yours to be.) A disease gene is said to have incomplete penetrance when individuals with the diseasecausing genotype do not always develop the disease phenotype. A good example of incomplete penetrance is retinoblastoma, in which 10% of obligate carriers develop no eye tumors. Variable expression refers to variation in the degree of severity of a genetic disease. An example of variable expression is neurofibromatosis type 1 (which, by the way, has 100% penetrance). Some individuals who have the NF1 gene have only a few neurofibromas and cafe-au-lait spots, while others can have hundreds of neurofibromas, as well as malignancies, scoliosis, seizures, psudarthrosis, optic gliomas, and pheochromocytomas. Another example of a disease with variable expression is cystic

Sample Problems & Essay Questions

fibrosis (CF), in which 15% of patients do not have pancreatic insufficiency. In addition, some CF patients have very severe lung disease and die within the first decade, while others can survive for several or more decades. (Other examples of diseases with variable expression include hemophilia A, osteogenesis imperfecta, and Marfan syndrome). Question 10: Explain the concept of imprinting. Use disease examples to illustrate your points. Answer: When a gene is imprinted, its expression varies depending on the parent from which it is inherited. Imprinting is strongly correlated with (and may be at least partially cause by) methylation of DNA sequences. Methylation is thought to inhibit the transcription of a gene, thus inactivating it. An example of imprinting is given by the Prader-Willi and Angelman syndromes, which are caused by alterations of genes on chromosome 15. Males normally transmit an active copy of the Angelman gene but an inactive (i.e., imprinted) copy of the Prader-Willi genes to their offspring. Males, in contrast, normally transmit an active copy of the Prader-Willi genes and an inactive (imprinted) copy of the Angelman gene to their offspring. A deletion of the paternally inherited region of chromosome 15 thus removes the active Prader-Willi genes and produces Prader-Willi syndrome. A deletion of the maternally inherited region of chromosome 15 removes the active Angelman gene and produces Angelman syndrome. Another example of imprinting is given by Beckwith-Wiedemann syndrome, which can be caused by the presence of two copies of the paternally derived IGF2 (insulin-like growth factor 2) gene. This can occur as a result of uniparental disomy. Because the maternally derived IGF2 gene isNim normal individuals have only one URprin SIted NG(ina TBct.ivCe),OM active copy of the gene(i.e., the single paternally inherited copy). Those having Two paternally inherited copies have twice the amount of IGF2 gene product, leading to some of the features of this disease (e.g., large size). Question 11: Match the pedigree with the most likely mode of inheritance. Note that complicating factors, such as reduced penetrance, may be present. Assume that the gene frequency of the disorder in the general population is very low. These answers may be used more than once.

a. autosomal dominant b. autosomal recessive

Sample Problems & Essay Questions c. X-linked recessive d. X-linked dominant e. mitochondrial Answer: c Question 12: Match the pedigree with the most likely mode of inheritance. Note that complicating factors, such as reduced penetrance, may be present. Assume that the gene frequency of the disorder in the general population is very low. These answers may be used more than once.

a. autosomal dominant b. autosomal recessive c. X-linked recessive d. X-linked dominant e. mitochondrial Answer: a

Jorde: Medical Genetics, 5th Edition Chapter 4: Autosomal Dominant and Recessive Inheritance Sample Problems & Essay Questions Question 1: Your class of 100 people has been typed for a two-allele polymorphism (alleles labeled 1 and 2), and the following 3 genotype counts were obtained: 1,1 30 1,2 50 2,2 20 What are the gene frequencies for alleles 1 and 2 in you class? Answer: F(1) = 0.55 F(2) = 0.45 Question 2: Suppose that the prevalence of hemophilia A (x-linked recessive) among the females of a population is 1/1,000,000. Based on this figure, what is the gene frequency in this population, and what would the prevalence be among males? Answer: 0.001, 0.001

.CthOatMhalf of the females who have Question 3: Continuing questioNnU2R , sSuI ppNoG seTnB ow hemophilia A are manifesting heterozygotes. Will this raise or lower the gene frequency estimate? Why? Answer: Lowers the estimate because half the females have only one copy of the gene. Question 4: A woman comes to your office for genetic counseling because her niece has cystic fibrosis (autosomal recessive). She is concerned that she might be a CF carrier. What is the probability that this woman is a heterozygous carrier for a cystic fibrosis mutation? Answer: 1/2 Question 5: A man and woman are both affected by an autosomal dominant disorder that is lethal in the embryonic period in homozygotes. The disease has 50% penetrance in heterozygotes. On average, what proportion of their live-born offspring will be affected? Answer: 2/3 x 1/2 = 1/3 Question 6: A woman who is a known heterozygous carrier of a PKU mutation marries her half second cousin (see pedigree). What is the probability that this couple will produce a child with PKU (autosomal recessive disorder)?

Sample Problems & Essay Questions

Answer: (1/2)^6 x 1/4 = 1/256 Question 7: A color-blind (X-linked) male with hemophilia A mates with a normal female. They produce a daughter with Turner syndrome who is not color blind. What is the daughter's risk of developing hemophilia? Answer: ~0 Question 8: A woman is affected with a mitochondrial disease. What proportion of her son's children will be affected with the disease? What proportion of her daughter's children will be affected with the disease? Answer: son's children: 0% daughter's children: 10N 0U %RSINGTB.COM Question 9: An autosomal dominant disorder is transmitted in each of these 3 pedigrees, and each pedigree member has been typed for a two-allele marker. Based on the genotypes in generation 3, what is the recombination rate between the disease locus and the marker locus?

Answer: 0.10 Question 10: Continuing question 9, what is the LOD score for the hypothesis that r = 0 in these families?

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Answer: LODs = log(16/1) + log (8/1) + log (0) = 1.2 + 0.9 + - infinity = - infinity Question 11: How has cloning and sequencing the cystic fibrosis gene led to a better understanding of causation, variable expression, and pleiotropy in this disorder? Answer: Cloning the cystic fibrosis gene led to the demonstration that this gene encodes a chloride ion channel necessary for the exit of chloride ions from specialized epithelial cells. Further study showed that the gene product also influences sodium channel activity in these cells. Mutations in the gene lead to an absence of or reduction in the activity of chloride channels. Consequently, chloride and sodium build up in airway and pancreatic cells. The salt imbalance, and its effect on water balance, help to explain why the airway and pancreas become obstructed with thick, heavy secretions. Pleiotropy is explained by the fact that the chloride defects affect cells in the airway. Pancreas, and sweat glands (in the latter, there is a defect of chloride reabsorption, which produces elevated sweat chloride levels). Different mutations in the gene N canR iat. ioCn inMexpression (allelic heterogeneity). U lead SIto NGvar TB O For example, the DF508 mutation results in a nearly complete lack of ion channels and nearly always produces pancreatic insufficiency when inherited in two copies. Other mutations may only reduce ion channel activity and thus do not necessarily produce pancreatic insufficiency. Question 12: Match the pedigree with the most likely mode of inheritance. Note that complicating factors, such as reduced penetrance, may be present. Assume that the gene frequency of the disorder in the general population is very low. These answers may be used more than once.

Sample Problems & Essay Questions a. autosomal dominant b. autosomal recessive c. X-linked recessive d. X-linked dominant e. mitochondrial Answer: b Question 13: Match the pedigree with the most likely mode of inheritance. Note that complicating factors, such as reduced penetrance, may be present. Assume that the gene frequency of the disorder in the general population is very low. These answers may be used more than once.

NURSINGTB.COM a. autosomal dominant b. autosomal recessive c. X-linked recessive d. X-linked dominant e. mitochondrial Answer: c Question 14: Match the pedigree with the most likely mode of inheritance. Note that complicating factors, such as reduced penetrance, may be present. Assume that the gene frequency of the disorder in the general population is very low. These answers may be used more than once.

Sample Problems & Essay Questions

a. autosomal dominant b. autosomal recessive c. X-linked recessive d. X-linked dominant e. mitochondrial Answer: a Question 15: Match each karyotype shown below with the appropriate description. The same answer can be used more than once. (Sorry that the images are not that clear)

Sample Problems & Essay Questions

a. Isochromosome b. Deletion c. Reciprocal translocation d. Robertsonian translocation e. Inversion Answer: e Question 16: Match each karyotype shown below with the appropriate description. The same answer can be used more than once. (Sorry that the images are not that clear)

a. Isochromosome b. Deletion c. Reciprocal translocation d. Robertsonian translocation e. Inversion Answer: d

Sample Problems & Essay Questions Question 17: Match each karyotype shown below with the appropriate description. The same answer can be used more than once. (Sorry that the images are not that clear)

a. Isochromosome b. Deletion c. Reciprocal translocation d. Robertsonian translocation e. Inversion Answer: b

Jorde: Medical Genetics, 5th Edition Chapter 5: Sex-linked and Nontraditional Modes of Inheritance Sample Problems & Essay Questions Question 1: A 30-year-old woman is phenotypically normal but had a brother who died from infantile Tay-Sachs disease (autosomal recessive lethal condition with 100% penetrance). What is the probability that this woman is a heterozygous carrier for TaySachs disease? Answer: 2/3 Question 2: A phenotypically normal couple with negative family history produces four children, three of whom have Marfan syndrome (autosomal dominant). What is the most likely explanation for this? Answer: Germline mosaicism Question 3: You have been called as an expert witness in the J.O. Sampson case. J.O. is accused of shoplifting a scalpel from a medical supply store. The shoplifter clumsily cut himself (herself) while stealing the scalpel, leaving a drop of blood at the scene of the crime. Mr. Sampson was typed for one VNTR locus and was found to have alleles 3 and 5 of this system. The blood samN plU eR wS asItyNpG edTaBn. dC wO asMfound to match J.O. for these two alleles. The frequencies of these alleles in the general population are 0.05 and 0.10. What is the probability that somebody in the general population would match the blood sample? Answer: 2pq = 0.1 x 0.1 = 0.01 Question 4: Two years later, the Sampson case is still in court. A second VNTR system has now been tested, and again a match is found between J.O. and the blood left at the crime scene. For this locus, J.O. is a homozygote for allele 2. This allele has a frequency of 0.10 in the general population. Combining the information from the two VNTR loci, what is the probability that someone in the general population would match the blood sample? (Remember that in question 3 Mr. Sampson was typed for one VNTR locus and was found to have alleles 3 and 5 of this system. The blood sample was typed and was found to match J.O. for these two alleles. The frequencies of these alleles in the general population are 0.05 and 0.10.) Answer: p^2 = 0.10^2 = 0.01 0.01(from above) x 0.01(from previous question) = 10^-4 = 0.0001

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Question 5: The accompanying pedigree shows two individuals who are affected with tyrosinase-negative albinism (autosomal recessive). What is the risk that their grandchild will be affected with this disorder?

Answer: 25% Question 6: What is the most likely explanation for the inheritance pattern shown here for neurofibromatosis type 1?

NURSINGTB.COM Answer: New mutation Question 7: In the accompanying pedigree, each individual has been assayed for a microsatellite repeat polymorphism that is known to be linked to an autosomal dominant disorder that is being transmitted in this family. The polymorphism has four alleles, labeled 1,2,3, and 4. Based on the genotypes of the offspring in generation III, what is the recombination fraction for the disease locus and the linked microsatellite system?

Answer: 25%

Sample Problems & Essay Questions

Question 8: Consider the accompanying pedigree, in which an autosomal dominant disease is segregating. Based on the genotypes in generation III, what is the LOD score for the hypothesis that the recombination fraction for the disease locus and the marker locus (with 2 alleles, 1 and 2) is zero?

Answer: -¥ Question 9: The accompanying pedigree shows the inheritance of galactosemia (autosomal recessive metabolic disorder) in a family. One child is affected with the disease, as shown. A second child has just been born, and his disease status is not yet known. The family has been tested for a two-allele RFLP that is very closely linked to the disease gene. The results are shown in the autoradiogram. Based on these results, what is the risk that the second child is also affected with galactosemia? (the numbers below each individual are labels to identify N thU em to. raC diO ogMram) RSonItNheGaTuB

Answer: 0

Question 10: The accompanying pedigree shows the inheritance of autosomal dominant breast cancer, a disorder whose penetrance is approximately 85% by age 85. A parent and one child are affected with the disorder, and the entire family has been typed for a tightly linked four-allele microsatellite polymorphism. Based on the genotypes shown in the autoradiogram, what is the risk that each of the other children in the family (numbered 46) will also develop breast cancer if they live to age 85?

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Answer: 4 = background = ~10% 5=~0 6 = 85% Question 11: You are on a quest to find the D&M gene (a cause of progressive dysmelodia). Using linkage analysis, you have localized the gene to a 10cM region of chromosome 7. How would you now proceed to isolate and clone the D&M gene? Answer: (from page 145 in the book) Suppose that we know the approximate location of a polymorphic marker that is tightly linked (less than 1 cM, or approximately 1 Mb) to the disease gene we wish to isolate. A technique commonly used to proceed toward the gene is called chromosome walking. DNA from the marker is used as a probe to pick out partially overlapping segments of DNA from a genomic library. The overlap can be determined by testing for hybridization between the probe and each DNA segment taken NUtheRSove IN GTping B.C from the library. Once identified, rlap DN OAMsegment itself is used as a probe to pick out another DNA segment from the genomic library with which it partially overlaps. In this way one uses partially overlapping DNA segments to "walk" along the chromosome until the disease gene itself is reached. Because we usually cannot be certain whether the disease gene is on one side of the marker or the other, chromosome walking typically proceeds in both directions away from the marker (a "bidirectional" walk). The DNA segments may be cloned into vectors, such as plasmids, cosmids, or yeast artificial chromosomes (YACs). Plasmids accommodate the smallest DNA inserts, whereas YACs accommodate the largest ones, about 1000 kb. These maps of contiguous DNA segments are often termed "contic" maps. Question 12: The autoradiogram shown here represents variation at which type of system? a. Restriction fragment length polymorphism (using Southern blotting). view image b. Microsatellite repeat polymorphism c. VNTR polymorphism (minisatellite) d. Rh blood group polymorphism e. Restriction fragment length polymorphism (using PCR) Answer: b

Jorde: Medical Genetics, 5th Edition Chapter 6: Clinical Cytogenetics: The Chromosomal Basis of Human Disease Sample Problems & Essay Questions Question 1: A population has been screened for mutations in the cystic fibrosis (autosomal recessive) gene using DNA testing. The test shows that 1/100 individuals in this population are heterozygous carriers of a cystic fibrosis (CF) mutation. Based on this figure, what is the expected proportion of affected individuals in this population? Answer: q = 1/200 p = ~1 2pq = 1/100 2q = 1/100 q^2 + 1/40,000 1/40,000 Question 2: Continuing question 1, if a known CF carrier in this population mates with somebody in the general population, what is the probability that the couple will produce a child affected with cystic fibrosis? Answer: 1/2 x 1/2 x 1/100 = 1/400 Question 3: Imagine that the known carrier in question 2 mates with his first cousin. What is the probability that this couple will produce a child affected with cystic fibrosis? Answer: 1/8 x 1/4 = 1/32 Question 4: You (or your significant other) have been identified as the culprit in a paternity suit. DNA testing has been performed to establish whether or not you are the father. Four VNTR loci were tested for you, the mother, and the baby in question. Unfortunately for you, the baby's alleles and your match for all four loci. The frequencies of these alleles in the general population are .05, .01, .01, and .02. What is the probability that somebody else in the general population could be the father of the baby? Answer: .05 x .01 x .01 x .02 = 10^-7 Question 5: A woman has had two sons who are affected with Duchenne muscular dystrophy (X-linked recessive). She also has two normal sons, and there is no other family history of the disease. This woman also has muscle weakness in her legs. What is the likely explanation for her muscle weakness? Answer: manifesting heterozygote Question 6: Consider two linked loci, labeled A and B. Each locus has two alleles, labeled 1 and 2. The frequencies of the alleles in a population are: A1 = 0.6, A2 = 0.4, B1 = 0.7, B2 = 0.3. If there is linkage equilibrium between these two loci in the population, what is the expected frequency of chromosomes carrying a combination of the A1 and B2 alleles?

Sample Problems & Essay Questions

Answer: (.6 x .3) = 0.18 Question 7: In the accompanying pedigree, each individual has been assayed for a microsatellite repeat polymorphism that is known to be linked to an autosomal dominant disorder that is being transmitted in this family. The polymorphism has six alleles, labeled 1,2,3,4,5, and 6. The genotypes in this family are shown in the autoradiogram. Based on the genotypes of the offspring in generation III, what is the recombination fraction for the disease locus and the linked microsatellite system?

Answer: 3/8 Question 8: Consider the accompanying pedigrees, in which an autosomal dominant disease is segregating. Based on the genotypes in generation III, what is the LOD score for the hypothesis that the recombination fraction for the disease locus and the marker locus (with 4 alleles, 1,2,3, and 4) is zero?

Answer: ((1/2)^4)/((1/4)^4) = 2^4 = 16

Sample Problems & Essay Questions

16:1 LOD = 1.2 64:1 LOD = 1.8 ~3 Question 9: A somatic cell hybridization panel is shown below. It indicates which clones yielded a positive hybridization signal for a DNA segment from a gene we wish to map. Based on the patterns in the hybridization panel, on which chromosome is the DNA segment located?

Answer: 20 Question 10: The accompanying pedigree shows the mating of two individuals who are both heterozygous carriers of mutations that can cause Wilson Disease, an autosomal recessive disorder of copper metabolism. The parents and their three offspring have each been typed for a closely linked microsatellite polymorphism. Based on the autoradiogram, what is the genotype of individual 5 (i.e., normal homozygote, heterozygote, or affected homozygote)?

Answer: Heterozygote Question 11: In the family shown below, several females have been diagnosed with breast cancer (the mother in generation I has died). Two of the females have been tested

Sample Problems & Essay Questions

for mutations in the BRCA1 gene on chromosome 17, and both of them have mutations in the gene. Yet a linkage analysis performed on the entire family yields a negative LOD score for linkage between a linked marker (r = .03) and breast cancer in this family. List two possible explanations for this finding. (2-3 sentences should be sufficient.)

Answer: Possible explanations include: (1) recombination between the marker and the disease locus, (2) locus heterogeneity or "nongenetic" causes such that other affected family members do not have BRCA1 mutations (3) incomplete penetrance or delayed age of onset in some family members Question 12: Describe amniocentesis, chorionic villus sampling, and in vitro fertilization diagnosis, discussing the relative advantages and disadvantages of each procedure.

NiU IaNl G Answer: Amniocentesis is the w thR drS aw ofTaBs. mC alO l aM mount of amniotic fluid from the uterine cavity. It is usually performed at approximately 16 weeks post-LMP and provides fetal cells (amniocytes) for karyotyping, diagnosis of some biochemical disorders, and DNA-based genetic diagnosis. It also provides an alpha-fetoprotein level, which can be used to diagnose neural tube defects. The rate of fetal demise as a consequence of the procedure is approximately 1/200. The primary advantages of the procedure are its accuracy and ability to diagnose a wide variety of conditions. A disadvantage is the fact that it is done relatively late during the pregnancy, and fetal cells often have to be cultured (which takes an additional week or more). Chorionic villus sampling (CVS) is the removal of a small piece of villus material, which contains fetal cells. It can be done either transabdominally or transcervically and is typically performed at 10-11 weeks post-LMP. An advantage is that it can be done earlier in the pregnancy than amniocentesis. Disadvantages include a higher rate of fetal loss (11.3%) and the possibility of misdiagnosis as a result of confined placental mosaicism. There is limited (but not entirely convincing) evidence that CVS performed before 10 weeks can cause limb reduction defects. In vitro fertilization (IVF) diagnosis is performed on an IVF-generated blastomere at the 8- or 16-cell stage. A single cell is removed (this does not harm the blastomere) and diagnosed using PCR to amplify the DNA. If the diagnosis yields a negative result (i.e., no disease) the blastomere can be implanted. If not, it can be stored or destroyed. The primary advantage is that pregnancy termination is not necessary. Disadvantages include the cost, difficulty of the procedure, and possibility for diagnostic error.

Sample Problems & Essay Questions Question 13: The autoradiogram shown here most likely represents variation at which type of system?

a. Restriction fragment length polymorphism b. Microsatellite repeat polymorphism c. VNTR polymorphism (minisatellite) d. Rh blood group polymorphism e. Each of the above is equally likely Answer: a

Jorde: Medical Genetics, 5th Edition Chapter 7: Biochemical Genetics: Disorders of Metabolism Sample Problems & Essay Questions Question 1: A population of 50 individuals has been assayed for a 4-allele microsatellite polymorphism, and the following genotype counts have been obtained: Genotype Count 1,1 4 1,3 8 1,4 3 2,3 5 2,4 9 3,3 4 3,4 6 4,4 11 Based on these genotype counts, what are the gene frequencies of alleles 1 and 2 Answer: F(1) = 0.19 F(2) = 0.14

Mardy-Weinberg equilibrium, what Question 2: Continuing questioN nU 1:RiS f tI hiN sG loT cuB s. isCinOH is the expected genotype frequency for the 1,1 genotype? Genotype Count 1,1 4 1,3 8 1,4 3 2,3 5 2,4 9 3,3 4 3,4 6 4,4 11 Answer: p^2 = 0.19^2 = 0.036 Question 3: A linkage study has been performed in which recombination frequencies have been measured for a disease locus (D) and two marker polymorphisms (A and B). The estimated recombination frequencies for each pair of loci are: A-B = 0.15; A-D = 0.04; B-D = 0.11. Based on these estimates, what is the order of the three loci on a chromosome? To which marker is the disease locus most closely linked? Answer: ADB Closest to A

Sample Problems & Essay Questions

Question 4: A man is affected with an X-linked dominant disorder. The penetrance of the disease genotype is 60%. What is the probability that his daughters will be affected with this disorder? Answer: 0.60 Question 5: ,Consider the accompanying pedigree, in which an autosomal dominant disease-causing gene is segregating. Each family member has been typed for a closely linked 2-allele RFLP. What is the risk that the offspring in generation III will inherit the disease-causing gene?

Answer: Uninformative family; Can't determine risk more accurately than 50% Question 6: In the accompanying pedigree, in which an autosomal recessive disease is N R I G B.ClyMlinked 6-allele microsatellite segregating, each member has beeUn tySpedNforTa closeO polymorphism. The genotypes are shown in the autoradiogram. What is the risk that individual 7 will develop the disease?

Answer: ~ 0

Sample Problems & Essay Questions

Question 7: In the accompanying pedigree, each individual has been assayed for a microsatellite repeat polymorphism that is known to be linked to an autosomal dominant disorder that is being transmitted in this family. The polymorphism has five alleles, labeled 1,2,3,4, and 5. What is the recombination fraction for the disease locus and the liked microsatellite system?

Answer: 2/8 = 0.25 Question 8: You are attempting to find a gene that causes autosomal dominant dysmelodia (this is a real condition -- tone deafness). You have chosen to label this gene as the D&M locus. Transmission of the D&M gene is shown in the accompanying pedigree. Family members haveNbeeRn tyIpedGforBa.4C ele marker locus (alleles are labeled U S N T -all OM 1,2,3, and 4). Based on the genotypes in generation III, what is the LOD score for the hypothesis that the recombination fraction for the disease locus and the marker locus is zero?

Answer: log(32) = ~ 1.5 Question 9: Your study has progressed, and a second family has now been studied and typed for the same polymorphic marker. You estimate the LOD score for this family, too. Considering the LOD scores in both families, how would you interpret your results?

Sample Problems & Essay Questions

Answer: LOD = - infinity NOT linked at r = 0. Could mean locus heterogeneity : NOT linked at r = 0 Question 10: A woman affected with retinoblastoma has borne a pair of monozygotic twins. One of the twins developed two retinoblastomas before age 5, while the other twin has never developed a retinoblastoma. What is the most likely explanation for this? Answer: Second hit did not occur; reduced penetrance Question 11: You are now employed by a well-known HMO, and a switch of babies in the hospital nursery is suspected. To determine whether "baby Smith" is truly the offspring of Mrs. Smith, the baby and Mrs. Smith have been typed for four VNTR systems (the other baby is not available for testing, and Mrs. Smith is unsure of the father of the baby). Mrs. Smith and the baby match for one allele in each of the four systems. The frequencies of the matching VNTR alleles in the general population are 0.01, 0.02, 0.05, and 0.1. To increase the acNcurR acyI of iG denB tif. icC atioM n, mother and baby have also been U S N T O sequenced for a portion of their mitochondrial DNA. They match for this sequence, too. This particular sequence is seen in 3% of the general population. Taking all of this information into account, what is the probability that a baby in the general population would have this combination of VNTR alleles and mitochondrial sequence? Answer: 0.02 x 0.02 x 0.05 x 0.1 x 0.03 = 0.00000003 = 3 x 10^-8 Question 12: Consider the following prenatal diagnostic techniques: amniocentesis, chorionic villus sampling, and the testing of fetal cells in the maternal circulation. Rank these three tests in terms of their potential for causing fetal loss, from least potential to greatest. Answer: fetal cells least risk amniocentesis chorionic villus sampling greatest risk Question 13: Discuss the genetic mechanisms responsible for antibody diversity. How do these mechanisms differ from those responsible for T-cell receptor diversity and MHC (major histocompatibility complex) diversity?

Sample Problems & Essay Questions

Answer: 1. Germ-line diversity. For the heavy and light chains, there are 100-200 variable (V) region segments, six joining (J) region segments, and, for the heavy chains, about 30 diversity (D) segments. 2. Somatic recombination. This is a process in which one V,J, and D segment is selected for the mature B lymphocyte (the deletion and recombination process is carried out by recombinases). This produces many possible combinations of V, J, and D segments. 3. Junctional diversity. Slight variations (insertions and deletions of nucleotides) occur at the junctions at which V,J, and D segments are joined. 4. Somatic hypermutation. V,J, and D segments mutate at a very high rate as B lymphocytes divide during the process of secondary differentiation. This provides higher affinity to foreign antigens. 5. Further diversity is provided by multiple combinations of different heavy and light chains. All of these mechanisms apply to T-cell receptors as well, although somatic mutation occurs at a lower rate than in B cells. MHC diversity occurs between individuals rather than within individuals and is the result only of germ-line differences between individuals.

Jorde: Medical Genetics, 5th Edition Chapter 8: Gene Mapping and Identification Sample Problems & Essay Questions Question 1: Your class of 100 individuals has been typed for a 3-allele microsatellite polymorphism, and the following genotypes were obtained. Genotype Count 1,1 4 1,2 18 1,3 24 2,2 8 2,3 28 3,3 18 Based on these genotype counts, what are the gene frequencies of alleles 1,2, and 3? Answer: F(1) = (8 + 18 + 24)/200 = 0.25 F(2) = (18 + 16 + 28)/200 = 0.31 F (3) = (24 + 28 + 36)/200 = 0.44 Question 2: Suppose you are studying a complex multifactorial disease, and you find that the concordance rate for this traN it U inRmSoI noNzG ygToB tic.tC wO inM s is identical to that of dizygotic twins. What is the heritability of this disease? Answer: 0 Question 3: A boy has severe hemophilia A (X-linked recessive). His sister also has hemophilia, but her disease is much milder. What is the most likely explanation for this difference in severity? Answer: Sister is a manifesting heterozygote Question 4: Women with Turner syndrome (45, X karyotype) sometimes reproduce. What is the risk of a 45, X karyotype in their offspring at conception? Answer: 1/4 Question 5: Consider the accompanying pedigree, in which an autosomal dominant disease-causing gene is segregating. Each family member has been typed for a linked 4allele microsatellite (recombination frequency = 0.02). What is the risk that the offspring in generation III will inherit the disease-causing gene?

Sample Problems & Essay Questions

Answer: 0.98 Question 6: In the accompanying pedigree, in which an autosomal recessive disease is segregating, each member has been typed for a closely linked 5-allele microsatellite polymorphism. The genotypes are shown in the autoradiogram. The disease genotype for individual 5 is shown. For individuals 6,7, and 8, indicate whether they are homozygous normal, heterozygous carrier, or homozygous affected.

Answer: 6 = Heterozygote 7 = Normal homozygote 8 = Homozygous affected Question 7: The president of a mythical country has just been named in a paternity suit. The defendant (labeled WC in the autoradiogram), the mother (labeled ML), and the baby (labeled "Buddy") have each been typed for two VNTR systems, as shown in the autoradiograms below. Each of these VNTR systems has four alleles. For the first VNTR, the frequencies of alleles 1,2,3, and 4 in the general population are 0.2, 0.4, 0.3, and 0.1, respectively. For the second VNTR, the frequencies of alleles 1,2,3, and 4 are 0.1, 0.1, 0.2, and 0.6, respectively. Answer 2 questions: Does the autoradiogram indicate that WC could be the father of Buddy? What is the probability that another male in the general population could be the father of Buddy?

Sample Problems & Essay Questions

Answer: 1) yes 2) 0.4 x 0.6 = 0.24

Question 8: In the accompanying pedigree, an autosomal dominant disease gene is being transmitted. Each family member has been typed for a 7-allele microsatellite polymorphism. Based on the genotypes in generation III, what is the recombination frequency for the disease locus and the microsatellite polymorphism?

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Answer: 1/10

Question 9: A large number of different mutations in the NF1 gene can cause neurofibromatosis type 1. Although NF1 has been cloned and sequenced, indirect genetic diagnosis is often used for this disease. Why? Answer: Too difficult, expensive, and time-consuming to test directly for all the different mutations. Question 10: (essay) Describe and compare direct and indirect genetic diagnosis (use at least one disease example for each type of diagnosis). What are the advantages and disadvantages of each approach?

Sample Problems & Essay Questions

Answer: Indirect diagnosis refers to the use of linkage analysis to determine whether an individual has inherited a disease-causing gene from a parent. It is used when a disease gene has been mapped but not yet cloned or, in some cases, when the mutations at a locus are very numerous or poorly characterized (e.g., Marfan syndrome, cystic fibrosis in some populations). With direct diagnosis, it is possible to examine the disease-causing mutation(s) directly through methods such as allele-specific oligonucleotide hybridization, restriction site analysis, DNA sequencing, or DNA chip hybridization. Many diseases are now diagnosed directly, including sickle cell disease, alpha-1antitrypsin deficiency, autosomal dominant breast cancer, and cystic fibrosis. Compared with indirect diagnosis, the advantages of direct diagnosis are that the mutation itself must be identified, some sequence information must be known, and large numbers of mutations can render the approach unfeasible. These disadvantages do not apply to indirect diagnosis, where the disease-causing locus need not be cloned and sequenced.

Jorde: Medical Genetics, 5th Edition Chapter 1: Background and History Multiple Choice 1. Achondroplasia has a high mutation rate. This is most likely the result of a. Paternal age effect b. Maternal age effect c. Large gene size d. Methylated CG dinucleotide e. 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 a. Haploinsufficiency b. Dominant negative c. Autosomal recessive d. Gain of function e. 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? a. Chromosome duplication b. Translocation c. Uniparental disomy d. Autosomal trisomy e. Autosomal monosomy Answer: c Correct Feedback: Prader Willi syndrome is effected by genomic imprinting. Thus, a uniparental disomy could cause the disease. Incorrect Feedback: This would not cause Prader Willi syndrome.

Multiple Choice 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? a. Testing for unmethylated CG islands b. Existence of a chromosome deletion in a patient c. Existence of trisomy in a patient d. DNA sequencing e. 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? a. Dementia b. Affective disorder c. New mutation d. Delayed age of onset e. Loss of motor control Answer: c Correct Feedback: This is rarely seen in Huntington 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 disease. 6. Which of the following is not a characteristic of osteogenesis imperfecta? a. Locus heterogeneity b. Allelic heterogeneity c. Pleiotropy d. Imprinting e. 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? a. Huntington disease

Multiple Choice

b. Cystic fibrosis c. Retinoblastoma d. Marfan syndrome e. 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? a. It is associated with methylation b. It can be diagnosed using a karyotype c. It is caused by a trinucleotide repeat expansion d. It displays nearly 100% penetrance e. 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 truNeUoR fF agN ilG eT XB sy.nC drO om Me. SrI 9. Which of the following diseases follow(s) a "2-hit model"? a. Osteogenesis imperfecta b. Adult polycystic kidney disease c. Cystic fibrosis d. Retinoblastoma e. 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 a. Advanced paternal age b. 13/15 translocation in one of the parents c. Extensive methylation of chromosome 13 d. Advanced maternal age

Multiple Choice e. B and D Answer: e Correct Feedback: e. Both advanced maternal age and a 13/15 translocation in one of the parents increases the recurrence risk for trisomy 13. Incorrect Feedback: a. Paternal age is usually not a factor in nondisjunction.b. This is true but is not the only true answer.c. This does not increase the recurrence risk for trisomy 13.d. This is true but is not the only true answer. 11. Which of the following is not correct about the XIST gene a. It is expressed only on the inactive X chromosome b. It produces an RNA product (which coats the inactivated X chromosome) but no protein product c. It is expressed during embryonic development d. It is expressed at twice the level in females as in males e. All of the above are true Answer: d Correct Feedback: d. The mRNA transcripts are not detected in normal males at all. Incorrect Feedback: a. This isN cor rect he.XCIST UR SIabo NGutTtB OMgene which is responsible for X inactivation in normal females.b. This is correct about the XIST gene which is responsible for X inactivation in normal females.c. This is correct about the XIST gene which is responsible for X inactivation in normal females.e. one of the above is false.

Jorde: Medical Genetics, 5th Edition Chapter 2: Basic Cell Biology: Structure and Function of Genes and Chromosomes Multiple Choice 1. Mutation in fibroblast growth factor receptor 3 (FGFR3) a. Retinoblastoma b. Achondroplasia c. Neurofibromatosis type 1 d. Huntington disease e. Marfan syndrome Answer: b Correct Feedback: b. Mutations in the fibroblast growth factor receptor 3 do cause achondroplasia. Incorrect Feedback: a. Retinoblastoma is caused by mutations in a tumor suppressor on chromosome 13. c. Neurofibromatosis type one is caused by a mutation of the neurofibromin gene (which may act as a tumor suppressor) on chromosome 17q d. Huntington disease is caused by a CAG expanded repeat on the distal tip of chromosome 4p. e. Marfan patients have mutations of the chromosome 15 gene encoding fibrillin, a connective tissue protein. 2. Abnormal binding of gene product to GAPDH (enzyme involved in glycolysis) a. Retinoblastoma b. Achondroplasia c. Neurofibromatosis type 1 d. Huntington disease e. Marfan syndrome Answer: d Correct Feedback: d. This is a characteristic of Huntington disease. Incorrect Feedback: a. Retinoblastoma is caused by mutations in a tumor suppressor on chromosome 13. b. Mutations in the fibroblast growth factor receptor 3 cause achondroplasia. c. Neurofibromatosis type one is caused by a mutation of the neurofibromin gene (which may act as a tumor suppressor) on chromosome 17q e. Marfan patients have mutations of the chromosome 15 gene encoding fibrillin, a connective tissue protein.

Multiple Choice

3. phosphorylation of gene product by cyclin-dependent kinases (CDK); binding of gene product to transcription factors such as E2F a. Retinoblastoma b. Achondroplasia c. Neurofibromatosis type 1 d. Huntington disease e. Marfan syndrome Answer: a Correct Feedback: a. The retinoblastoma gene product is phosphorylated by a CDK and then binds to transcription factors. Incorrect Feedback: b. Mutations in the fibroblast growth factor receptor 3 cause achondroplasia. c. Neurofibromatosis type one is caused by a mutation of the neurofibromin gene (which may act as a tumor suppressor) on chromosome 17q d. Huntington disease involves abnormal binding of gene product to GAPDH (enzyme involved in glycolysis) e. Marfan patients have mutations of the chromosome 15 gene encoding fibrillin, a connective tissue protein. 4. Mutations in fibrillin gene a. Retinoblastoma b. Achondroplasia c. Neurofibromatosis type 1 d. Huntington disease e. Marfan syndrome Answer: e Correct Feedback: e. Marfan patients have mutations of the chromosome 15 gene encoding fibrillin, a connective tissue protein. Incorrect Feedback: a. The retinoblastoma gene product is phosphorylated by a CDK and then binds to transcription factors. b. Mutations in the fibroblast growth factor receptor 3 cause achondroplasia. c. Neurofibromatosis type one is caused by a mutation of the neurofibromin gene (which may act as a tumor suppressor) on chromosome 17q d. Huntington disease involves abnormal binding of gene product to GAPDH (enzyme involved in glycolysis) 5. Which of the following could produce an XY female? a. Deletion of the Sry gene b. Point mutation in the Sry gene c. Translocation of the Sry gene to the X chromosome during meiosis in the father d. None of the above

Multiple Choice

e. All of the above Answer: e Correct Feedback: e. All of the above could produce an XY female. Incorrect Feedback: a. This is true, but it is not the only true answer. b. This is true, but it is not the only true answer. c. This is true, but it is not the only true answer. d. There are true answers. 6. Which of the following is not a characteristic of cystic fibrosis? a. Chloride channel defect b. Hyperabsorption of intracellular sodium c. Elevated sweat chloride d. Fibrous ovarian cysts e. Pancreatic insufficiency Answer: d Correct Feedback: This is not a characteristic of cystic fibrosis. Incorrect Feedback: This is a characteristic of cystic fibrosis.

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7. Each of the following chromosome abnormalities involves a 20 megabase region of the long arm of chromosome 5 (5q). Which abnormality is most likely to cause severe disease? a. Deletion of the region b. Duplication of the region c. A balanced translocation involving the region (i.e., in the translocation carrier) d. Pericentric inversion e. Paracentric inversion Answer: a Correct Feedback: This is the most likely to cause severe disease. Incorrect Feedback: This can cause problems, but they are not as likely to be as severe as a deletion of the entire gene. 8. Which of the following diseases is a good example of locus heterogeneity? a. Prader-Willi syndrome b. Myotonic dystrophy c. Osteogenesis imperfecta d. Duchenne muscular dystrophy e. Hemophilia A

Multiple Choice

Answer: c Correct Feedback: c. Locus heterogeneity is where genes have more than on discernible effect. OI effects bones, teeth, and sclera. Incorrect Feedback: a. Prader-Willi syndrome is a good example of genomic imprinting. b. Myotonic dystrophy is a good example of anticipation. d. Duchenne muscular dystrophy is an X-linked disease. e. Hemophilia A is an X-linked disease. 9. Why are some autosomal dominant disorders (e.g., Marfan syndrome) seen more commonly in the offspring of older fathers? a. Replication errors accumulate as sperm-producing stem cells continue to divide b. Rate of nondisjunction increases in older males c. Recombination rates increase in older males d. All spermatocytes are produced during male embryonic development, so older males produce older sperm cells e. None of the above Answer: a Correct Feedback: a. This is wNhyUR som auGtos om .aCl do SIe N TB OMminant disorders are seen more commonly in the offspring of older fathers. Incorrect Feedback: b. This is seen in older mothers. c. This is not true. d. This is not true. e. There is a correct answer 10. A woman with phenotypically normal parents has two brothers with Duchenne muscular dystrophy. She experiences mild muscle weakness in her legs. Which of the following mechanisms is most likely to be directly involved? a. Germline mosaicism b. Skewed X inactivation c. Mutation near the pseudoautosomal region of the Y chromosome d. New mutation in this woman e. Nondisjunction of her mother's X chromosomes Answer: b Correct Feedback: b. This is most likely to be directly involved. Incorrect Feedback: a. This wouldn't explain why a heterotroph would manifest the disease.

Multiple Choice

c. A female would not have a Y chromosome. d. If this were the case it would be unlikely that her brothers had the disease. e. Duchenne muscular dystrophy is not a chromosomal disease. 11. Consider a fetus affected with one of the following conditions. For which condition is spontaneous loss during pregnancy most likely? a. Down syndrome b. Neurofibromatosis type 1 c. Retinoblastoma d. Huntington disease e. Trisomy 18 Answer: e Correct Feedback: e. Chromosomal abnormalities are the number one cause of fetal loss, and trisomy 18 is less compatable with survival than trisomy 21. Incorrect Feedback: a. Chromosomal abnormalities are the number one cause of fetal loss, but trisomy 18 is less compatable with survival than trisomy 21 b. Chromosomal abnormalities are the number one cause of fetal loss. c. Chromosomal abnormalities are the number one cause of fetal loss. d. Chromosomal abnormalities are the number one cause of fetal loss.

Jorde: Medical Genetics, 5th Edition Chapter 3: Genetic Variation: Its Origin and Detection Multiple Choice 1. Which of the following would not tend to raise mutation rates for single-gene disorders in humans? a. CG dinucleotides within the gene b. elevated paternal age c. caffeine exposure d. large genes e. all of the above are known to raise mutation rates in humans Answer: c Correct Feedback: c. Caffein exposure would not raise rates. Incorrect Feedback: a. This would raise mutation rates. b. This would raise mutation rates. d. This would raise mutation rates. e. One of the above does not raise mutation rates. 2. Which of the following diseaN seU sR reS suI ltN s fG roTmBf. auCltO yM DNA repair? a. neurofibromatosis type 1 b. retinoblastoma c. xeroderma pigmentosum d. osteogenesis imperfecta e. hemophilia A Answer: c Correct Feedback: c. This disease results from faulty DNA repair. Incorrect Feedback: a. Neurofibromatosis type 1 is an inherited mutation. b. Retinoblastoma is caused by mutations (two-hit model). d. This disease does not result from faulty DNA repair. e. This disease does not result from faulty DNA repair. 3. Which of the following does not pertain to cystic fibrosis (CF)? a. consanguinity is commonly seen in parents with CF offspring b. variable expression c. c. more than one mutation at the CF locus can cause the disease d. potential candidate for gene therapy e. pleiotropy

Multiple Choice

Answer: a Correct Feedback: Consanguinity is not commonly seen in CF. Incorrect Feedback: This is seen in CF. 4. Which of the following is not true of Huntington disease? a. triplet repeat expansion is observed b. age of onset is delayed c. choreic movements are seen d. recurrence risk for offspring of an affected parent is 50% e. offspring of affected mothers have earlier age of onset than those of affected fathers Answer: e Correct Feedback: The opposite is true. Offspring of affected fathers have earlier age of onset than those of affected mothers. Incorrect Feedback: This is true of Huntington disease. 5. A likely explanation for the fact that some 45,X conceptions (Turner syndrome) survive to term is a. mosaicism in the fetus sord b. delayed age of onset of the diN URerSINGTB.COM c. germline mosaicism in one of the parents d. imprinting on the X chromosome e. incomplete X inactivation Answer: a Correct Feedback: a. This would explain why a Turner syndrome baby could survive to term. Incorrect Feedback: b. Delayed age of onset is irrelevant before the babies birth. c. Germline mosaicism in the parent would lead to the same conclusions as an inherited defect. d. Imprinting would not help survival rates. e. X-inactivation would not help survival rates. 6. Which of the following is not a diagnostic feature of neurofibromatosis type 1? a. neurofibromas b. positive family history c. benign hamartomas of the iris d. melanomas e. cafe-au-lait spots

Multiple Choice Answer: d Correct Feedback: Malignant tumors are rarely seen with NF1. Incorrect Feedback: This is a diagnostic feature of neurofibromatosis type 1. 7. Which of the following is not true of the dystrophin protein? a. binds actin b. binds to sarcoglycan/dystroglycan complex c. c. can be assayed to diagnose Duchenne muscular dystrophy d. is absent in patients having Becker muscular dystrophy e. composes only a very tiny fraction of the mass of a muscle cell Answer: d Correct Feedback: It is not absent, only mutated. Incorrect Feedback: This is true of the dystrophin protein. 8. In which of the following individuals would you not expect to see a Barr body? a. XX male b. 45,X female c. XY female d. a and b e. b and c Answer: e Correct Feedback: e. B and c are both cases where you would not see Barr bodies. Incorrect Feedback: a. You would see a Barr body here. b. This is correct but not the only one. c. This is correct but not the only one. d. A is wrong and b and c are correct. 9. Which of the following is not often seen in the individual with Klinefelter syndrome? a. webbed neck b. increased stature c. diminished IQ (on average) d. sterility e. gynecomastia Answer: a Correct Feedback: This is seen with Turner syndrome.

Multiple Choice

Incorrect Feedback: This is seen with Klinefelter syndrome. 10. What is the most likely explanation for the expression of hemophilia A in a female who is a heterozygote for an X-linked mutation in the factor VIII gene? a. nonsense mutation causing truncated protein b. her father is affected, and her mother is a heterozygous carrier c. a high proportion of the X chromosomes carrying the mutation are active in this female d. one of her X chromosomes carries the SRY gene e. X inactivation does not affect the entire chromosome Answer: c Correct Feedback: This would lead to expression in a heterozygote. Incorrect Feedback: This would not lead to expression in a heterozygote. 11. Which of the following is least likely to increase the recurrence risk of trisomy 13 in a family? a. advanced maternal age b. mother carries a 13/14 Robertsonian translocation c. father carries a 13/14 Robertsonian translocation d. germline mosaicism in the mother in which some cells are 47,XX,+13 e. advanced paternal age Answer: e Correct Feedback: Trisomies are usually derived maternally. Incorrect Feedback: This would increase the recurrence risk.

Jorde: Medical Genetics, 5th Edition Chapter 4: Autosomal Dominant and Recessive Inheritance Multiple Choice 1. Which of the following mutation types is expected to produce the mildest form of disease? a. Mobile element insertion b. frameshift deletion c. nonsense mutation d. missense mutation e. frameshift insertion Answer: d Correct Feedback: d. Missence mutations are most likely to be milder because they only affect one amino acid and not the whole protein Incorrect Feedback: a. Mobile element insertions are not as likely to produce a mild form of disease because they can cause framshifts or nonsense mutations that disrupt the whole protein. b. Frameshift deletions are not as likely to produce a mild form of the disease because they affect a large portion of theNpUroRteSinI. NGTB.COM c. Nonsense mutations cause premature stopping of translation thereby giving a portion of the protein e. Framshift insertions affect the whole protein that is downstream of the insertion point causing a more serious anomoly 2. Individuals who inherit two active copies of the insulin-like growth factor 2 gene (Igf2)-- one from their mother and one from their father--are at increased risk for developing the Wiedemann-Beckwith syndrome (large size at birth, large tongue, increased incidence of kidney tumors). This situation is an example of: a. autosomal recessive inheritance b. X-linked dominant inheritance c. imprinting d. mitochondrial inheritance e. relaxation of imprinting Answer: e Correct Feedback: e. Weidemann-Beckwith syndrome can be caused by relaxation of imprinting leading to an overproduction of Igf2. Incorrect Feedback: a. Weidemann-Beckwith syndrome is actually an autosomal dominant condition with variable expression and incomplete penetrance.

Multiple Choice

b. Weidemann-Beckwith syndrome shows no signs of being X-linked, and is actually assosiated with the chromosome 11p15.5 region c. Prader-Willi and Angelman syndromes are associated with imprinting. WeidemannBeckwith syndrome is actually associated with a relaxation of imprinting. d. Weidemann-Beckwith syndrome shows no signs of mitochondrial inheritance in that it can be inherited by the father as well as the mother. 3. Which of the following features would you be least likely to observe in neurofibromatosis type 1. a. cafe-au-lait spots b. Lisch nodules c. malignant tumors d. neurofibromas e. previous family history of the disorder Answer: c Correct Feedback: c. Patients with neurofibromatosis type 1 rarely have malignant tumors. Incorrect Feedback: a. Cafe-au-lait spots are a common characteristic of neurofibromatosis type 1 b. Lisch nodules are a common characteristic of adults with neurofibromatosis type 1 d. Neurofibromas are a commonNch arac stic ofibromatosis type 1 UR SIteri NG TBof.nCeur OM e. Most patients have a previous family history of the disease. 4. Concerning retinoblastoma, which of the following is not predicted by the two-hit model? a. sporadic tumors will be unifocal b. inherited tumors will be multifocal c. penetrance is incomplete d. two copies of the gene must be disabled for tumor expression to occur e. imprinting will be observed Answer: e Correct Feedback: Imprinting involves the methylation of the gene by either the mother or the father and is not associated with the two-hit model. Incorrect Feedback: This is predicted by the two-hit model. 5. Which of the following will yield the highest recurrence risk for Down syndrome in a family? a. 45-year-old mother b. 65-year-old father c. 25-year-old mother with a previous child with trisomy 21

Multiple Choice d. 20-year-old mother who carries a 21/14 Robertsonian translocation and has had no previous children with Down syndrome e. 20-year-old father who carries a 21/14 Robertsonian translocation and has had no previous children wit Down syndrome Answer: d Correct Feedback: d. a 21/14 Robertsonian translocation is one cause of Downs syndrome. Incorrect Feedback: a. A 45 year old mother has around a 2% chance of having a baby with down syndrome, but there is a better answer. b. The mother contributes the extra chromosome in 95% of the cases. c. Most cases are from individual nondisjunction events. e. The mother contributes the extra chromosome in 95% of the cases. 6. In which of the following chromosome disorders is the extra chromosome contributed in nearly equal proportions by the mother and the father? a. 47, XXY b. trisomy 21 c. trisomy 13 d. trisomy 18 e. 47, XYY Answer: b Correct Feedback: a. The extra X chromosome is derived maternally in about 60% of the cases which is closer than the other possibilities. Incorrect Feedback: b. 95% of trisomy 21 cases are maternally derived. c. Trisomy 13 is a lot more commonly derived from the mother. d. Trisomy 18 is a lot more commonly derived from the mother. e. With 47,XYY the extra chromosome comes from the father. 7. A crossover event that places the SRY gene on the X chromosome can cause a. an XX male b. a male who has features similar to those of Klinefelter syndrome c. an XY female d. all of the above e. none of the above Answer: d Correct Feedback: d. All of the above can occur. Incorrect Feedback: a. This is correct but there are other right answers as well.

Multiple Choice

b. This is correct but there are other right answers as well. c. This is correct but there are other right answers as well. e. There is a correct answer. 8. Which of the following is not often seen in the child with Down syndrome? a. congenital heart defect b. hypertonia c. mental retardation d. respiratory infections e. simian crease Answer: b Correct Feedback: Hypotonia is seen, not hypertonia. Incorrect Feedback: This is seen in Down syndrome. 9. What is the best explanation for the muscle weakness seen in 8-10% of females who are heterozygotes for the Duchenne muscular dystrophy gene? a. variable expression of the disease gene b. X-linked recessive inheritance c. a high proportion of the X chromosomes carrying the mutation are active in this female d. relaxation of imprinting ntI ireNcGhT roB m. osCoO mM e e. X inactivation does not affectNthUeReS Answer: c Correct Feedback: c. A high proportion of the X chromosomes carrying the mutation being active is a good explanation for this. Incorrect Feedback: a. Variable expression of the disease gene does not explain this. b. Being X-linked only explains why female heterozygotes normally do not have symptoms. d. This is not an example of imprinting. e. This is true, but it does not explain the phenomenum. 10. It has been suggested that schizophrenia is more severe and has an earlier age of onset in the more recent generations of schizophrenia families. If so this would be an example of: a. the two-hit model b. imprinting c. delayed age of onset d. anticipation e. increased numbers of mutagens in more recent generations Answer: d

Multiple Choice

Correct Feedback: d. Anticipation would explain an earlier age of onset and greater severity. Incorrect Feedback: a. The two-hit model would explain incomplete penetrance, but not earlier age of onset and greater severity. b. Imprinting does not explain this. c. Delayed age of onset would not lead to greater severity, and it contradicts the questions part about earlier age of onset. e. Increased numbers of mutagens in more recent generations is not the best answer. 11. Which of the following is true of chromosome abnormalities? a. They are the leading known cause of spontaneous pregnancy loss b. in general, monosomies have more severe consequences than trisomies c. most of the aneuploidies seen among live births increase with maternal age d. none of the above e. all of the above Answer: e Correct Feedback: e. All of the above are true. Incorrect Feedback: a. This is true, but it is not the only true answer. b. This is true, but it is not the oN nly URtrue SIans NGwer TB. .COM c. This is true, but it is not the only true answer. d. There is a true answer.

Jorde: Medical Genetics, 5th Edition Chapter 5: Sex-linked and Nontraditional Modes of Inheritance Multiple Choice 1. Sickle-cell disease is the result of a single nucleotide substitution that produces a single amino acid substitution. This is best described as a a. frameshift mutation b. nonsense mutation c. splice-site mutation d. missense mutation e. none of the above Answer: d 2. Which of the following is not true of imprinting? a. It is often associated with methylation. b. Diseases involving imprinting genes can result from either over-expression or underexpression of the gene product. c. It can be specific to only certain tissues. d. Imprinting results in differential expression of a gene, depending on the gender of the individual who expresses the disease. e. Imprinting can affect multipleNgUeR neS sI inNaGsT inB gl. eC chO roM mosome region. Answer: d 3. What is a likely explanation for the high prevalence of cystic fibrosis in European populations? a. Most of the disease genes are hidden in heterozygotes. b. The locus has a high mutation rate. c. Many different mutations can cause cystic fibrosis. d. Inbreeding is common among Europeans. e. Heterozygotes may have an advantage because of increased resistance to typhoid fever. Answer: e 4. In one form of familial isolated growth hormone deficiency, deletion of an exon of a gene on chromosome 17 alters the protein product. In heterozygotes, this protein product then binds with the normal protein product encoded by the normal copy of the gene on chromosome 17, disabling the normal growth hormone molecule. This is best described as an example of a. dominant negative effect b. haploinsufficiency c. gain of function mutation d. loss of function mutation

Multiple Choice e. none of the above Answer: a 5. Which of the following characterize adult polycystic kidney disease? a. locus heterogeneity b. gain of function mutations c. 2-hit model of causation d. a and b e. a and c Answer: e 6. The mutation that causes Huntington disease is best described as a. a CAG repeat expansion that occurs in the 3' untranslated region of the gene b. a CAG repeat expansion that produces a protein that tends to form aggreagates in the nucleus of the cell c. a CAG repeat expansion that leads to haploinsufficiency and thus neuronal death d. a CAG repeat expansion that causes earlier onset of the disease in males than in females e. all of the above Answer: b 7. Which of the following is not a characteristic of hemochromatosis? a. high prevalence in European populations b. locus heterogeneity c. pleiotropy d. different penetrance in males and females e. early diagnosis can lead to effective treatment and prevention Answer: d 8. A phenotypically normal woman has had two children with trisomy 13. Which of the following scenarios would be least likely to result in this recurrence? a. she is a germ-line mosaic for trisomy 13 b. she carries a Robertsonian translocation of chromosome 13 to chromosome 14 c. she carris a Robertsonian translocation of chromosome 21 to chromosome 14 d. she has had both children in her late 40s e. she carries a Robertsonian translocation of chromosome 13 to chromosome 15 Answer: c 9. Which of the following is not a feature of Down syndrome? a. hypotonia (poor muscle tone) b. reduced IQ

Multiple Choice c. association with elevated maternal age d. increased risk of leukemia e. cleft lip/cleft palate Answer: e 10. Uniparental disomy in a live birth is caused by which of the following mechanisms? a. trisomic conception followed by subsequent loss of the chromosome that was contributed in single copy by one parent. b. triploid conception followed by subsequent loss of the extra set of chromosomes c. fusion of an egg cell and a polar body, resulting in a conception with no paternal genetic contribution d. monosomic conception followed by the gain of a chromsome e. all of the above Answer: a 11. X inactivation a. involves activation of the XIST gene on the X chromosome that becomes inactive. b. does not affect the entire inactivated X chromosome c. is associated with methylation of the inactive X chromosome. d. can lead to disease symptoms for an X-linked recessive disorder in a heterozygous female if the proportion of inactivated paternal and maternal chromosomes deviated strongly from 50/50. e. all of the above Answer: e

Jorde: Medical Genetics, 5th Edition Chapter 6: Clinical Cytogenetics: The Chromosomal Basis of Human Disease Multiple Choice 1. Which of the following is not true od the trinucleotide repeat expansions that cause the neurodegenerative disorders Huntington disease and the spinocerebellar ataxias? a. they typically involve large expansions to several hundred or several thousand repeat units. b. They cosist of CAG repeats located within exons c. They are considered to be gain of function mutations. d. Expansion is more likely to occur when the repeat is passed through the father than through the mother e. In at least some cases, the mutation causes a buildup of protein aggregates in the cell nucleus. Answer: a 2. Segmental neurofibromatosis, in which disease features are seen in only part of the body, would best be described as a. inherited mutation b. new mutation c. germline mosaicism d. Somatic mosaicism e. none of the above Answer: d 3. Which of the following features is not true of achondroplasia? a. nearly all disease-causing mutations occur at a single methylated CG dinucleotide within the gene b. surgical repair is possible for this disorder c. it is caused by mutations in a fibroblast growth factor receptor gene d. most cases are the result of a new mutation e. homozygotes and heterozygotes are equally severely affected Answer: e 4. Which of the following is true of the Utah population? a. elevated rates of inbreeding are seen b. elevated prevalence of PKU, cystic fibrosis, and hemochromatosis c. relatively high rates of genetic drift d. genetically similar to northern European populations e. all of the above

Multiple Choice

Answer: d 5. In which of the following chromosome abnormalities is mosaicism most likely to be seen? a. Klinefelter syndrome b. Down syndrome c. XXX syndrome d. Turner syndrome e. Translocation Down Syndrome Answer: d 6. Wich of the following best explains variable expression in mitochondrial diseases? a. locus heterogeneity b. heterozygosity c. heteroplasmy d. modifier loci e. imprinting Answer: c 7. Which of the following would be most likely to produce an imbalance in the amount of essential genetic material in the carrier? a. Robertsonian translocation b. Paracentric inversion c. Pericentric inverison d. Reciprocal translocation e. Isochromosome Answer: e 8. Which of the following statements regarding chromosome abnormalities is true? a. Structural abnormalities increase with paternal age, while abnormalities of chromosome number increase with maternal age b. All chromosome abnormalities increase wit maternal age c. For all abnormalities of chromosome number, the extra or missing chromosomes are most often the result of meiotic error in the mother d. all of the above e. none of the above Answer: a,c,d,e 9. Which of the following conditions is most compatible with survival to term? a. trisomy 13 b. trisomy 18 c. monosomy X (45,X Turner syndrome)

Multiple Choice d. monosomy 21 e. trisomy 21 Answer: e

Jorde: Medical Genetics, 5th Edition Chapter 7: Biochemical Genetics: Disorders of Metabolism Multiple Choice 1. It has been suggested that cystic fibrosis (autosomal recessive) has a high prevalence in some populations because heterozygotes are resistant to the effects of chloride-secreting diarrhea. This is best described as an example of a. Mutation b. Gene flow c. Genetic drift d. Natural selection e. Linkage disequilibrium Answer: d Correct Feedback: d. This is an example of Natural Selection Incorrect Feedback: a. This is not a mutation b. This is not an example of gene flow c. This is not an example of genetic drift e. This is not an example of Linkage disequilibrium 2. Which of the following is not true of genetic diagnosis using fetal cells in the maternal circulation? a. PCR is used to amplify DNA from the fetal cell b. The procedure involves no risk to the fetus c. The procedure involves virtually no risk to the mother d. The procedure is more accurate than amniocentesis e. FISH analysis can be used to detect aneuploidy in the fetal cells Answer: d Correct Feedback: Amniocentesis is actually more accurate. Incorrect Feedback: This is true. 3. Using linkage analysis, you have mapped a disease gene to a 1 magabase (Mb) region of a specific chromosome. Which of the following approaches would be least useful in identifying and cloning the gene? a. Single strand conformation polymorphisms (SSCP) analysis b. Testing for cross-species conservation c. DNA sequencing d. Isolation of CG islands e. Radioactive in situ hybridization

Multiple Choice

Answer: e Correct Feedback: This would be useful. Incorrect Feedback: This would be useful. 4. Which of the following is a major difference in the mechanisms for generating diversity in T cell receptors and B cell immunoglobulins (antibodies)? a. Somatic hypermutation is seen in immunoglobulin genes but not in T cell receptor genes b. There are multiple variable region genes for immunoglobulins but not for T cell receptors c. Somatic recombination is seen only in immunoglobulin genes d. Junctional diversity is generated only in T cell receptor genes e. Junctional diversity is generated only in immunoglobulin genes Answer: a Correct Feedback: This is the major difference. Incorrect Feedback: This is true for both. maj ity locus) allelic diversity among 5. Why is there so much MHC (N URorShIisto NGcom TBp.atCibil OM individuals in populations? a. This region is especially susceptible to the effects of genetic drift b. The MHC region has a high level of somatic hypermutation c. Diversity enables the population to combat a larger number of different pathogens d. There are hundreds of different MHC loci, and they are shuffled by somatic recombination e. MHC diversity ensures that most tissue grafts will be rejected. Answer: c Correct Feedback: This is the real reason why ther is so much allelic diversity. Incorrect Feedback: This is not the reason. 6. A likely explanation for autoimmune disease is a. Repeated infection by the same microbe eventually stimulates an autoimmune response b. Depletion of T cell activity as a result of interleukin deficiency c. Depletion of B cell activity as a result of interleukin deficiency d. Lack of a memory B cell response e. Mimicry of self proteins by a foreign pathogen Answer: e

Multiple Choice

Correct Feedback: This is the most likely explanation for an autoimmune disease. Incorrect Feedback: This is not very likely. 7. A Northern Blot is used to a. Test polymorphisms in linkage analysis b. Analyze protein variation c. Analyze DNA sequence d. Analyze gene expression in different tissues e. Analyze a Southern blot that has mistakenly been run upside down Answer: d Correct Feedback: d. A Northern blot is a gene expression assay in which mRNA on a blot is hybridized with a labeled probe. Incorrect Feedback: a. This is not a possible use. b. This requires a Western Blot. c. This requires a Southern Blot. e. Southern Blots use DNA and Northern blots use mRNA. Therefore they are not interchangeable. e of osom 8. Which of the following is truN URaut SI NGalTBdo.mCina OMnt breast cancer? a. It is characterized by locus heterogeneity b. It accounts for nearly half of all breast cancer cases in the United States c. It can be detected by hybridization with a single oligonucleotide probe d. Penetrance is close to 100%, with nearly all gene carriers developing breast cancer by age 80 e. Autosomal dominant breast cancer affects females but not males Answer: a Correct Feedback: This is a characteristic of autosomal dominant breast cancer. Incorrect Feedback: This is not true. 9. Which of the following is not true of type 2 diabetes (non-insulin dependent diabetes) a. This form of diabetes is more highly heritable than type 1 diabetes b. Susceptibility to type 2 diabetes is partially due to the MHC and insulin genes c. Diet and exercise can decrease susceptibility to this form of diabetes d. MODY (maturity onset of diabetes in the young) is considered a highly heritable subset of this form e. This type of diabetes typically has a later age of onset than type 1 diabetes Answer: b

Multiple Choice

Correct Feedback: This is not involved in the susceptibility to type 2 diabetes. Incorrect Feedback: This is true. 10. Huntington disease is thought to be caused by a gain-of-function mutation. Which type of gene therapy would be potentially effective in treating this mutation? a. Replacement therapy with retroviral vectors b. Replacement therapy with adenovirus vectors c. Replacement therapy with adeno-associated vectors d. Antisense therapy e. All of the above Answer: d Correct Feedback: d. This would be potentially effective. Incorrect Feedback: a. Replacement therapy is not very effective against gain-offunction mutations. b. Replacement therapy is not very effective against gain-of-function mutations. c. Replacement therapy is not very effective against gain-of-function mutations. e. One of the above is true. ifiC da) 11. A neural tube defect (anenceNpha URlySoIr NspGina TBb. OMcould be detected by a. Amniocentesis b. Chorionic villus sampling c. Ultrasound d. A and B e. A and C Answer: e Correct Feedback: e. A and c will detect a neural tube defect. Incorrect Feedback: a. C is also right. b. This will not detect a neural tube defect. c. A is also right. d. A and c are right, not b. 12. Which of the following is not an indication for prenatal diagnosis by amniocentesis? a. Previous child with a serious chromosome abnormality b. Both parents are heterozygous carriers of a mutation that causes Tay-Sachs disease c. Both parents have bipolar affective disorder (manic depression) d. Maternal age > 35 e. Previous child or children with a neural tube defect

Multiple Choice Answer: c Correct Feedback: Amniocentesis would not help to detect this. Incorrect Feedback: Amniocentesis would help in this case. 13. Which of the following would not be involved in a quantitative trait locus analysis? a. Linkage analysis b. Breeding of experimental animals c. Search for human homologs with a non-human probe d. Estimation of heritability e. Positional cloning of a disease-causing gene Answer: d Correct Feedback: This is not involved. Incorrect Feedback: This would be involved. 14. Which of the following genetic abnormalities is not associated with Alzheimer disease? a. Mutations in the beta-amyloid precursor protein (BAPP) gene b. Presenlilin mutations c. Trisomy 21 d. Apolipoprotein E e4 allele e. LDL receptor mutations Answer: e Correct Feedback: This is not associated with Alzheimer disease. Incorrect Feedback: This is associated with Alzheimer disease. 15. Match each phrase with the most appropriate description. Answers can be used more than once. Age-related macular degeneration a. BRCA1 and BRCA2 (breast cancer) gene products b. HOX (homeobox) gene family c. Leptin mutations d. Stargardt's disease mutations e. Glucokinase mutations Answer: d Correct Feedback: d. This is seen with age-related macular degeneration

Multiple Choice

Incorrect Feedback: a. This is seen in interactions with the Rad51 DNA repair system b. This is seen in transcription factors involved in limb development c. This is seen in obesity. e. This is more common with Maturity onset diabetes of the young (MODY) 16. Match each phrase with the most appropriate description. Answers can be used more than once. Interact with the Rad51 DNA repair system a. BRCA1 and BRCA2 (breast cancer) gene products b. HOX (homeobox) gene family c. Leptin mutations d. Stargardt's disease mutations e. Glucokinase mutations Answer: a Correct Feedback: a. This is seen in interactions with the Rad51 DNA repair system Incorrect Feedback: b. This is seen in transcription factors involved in limb development c. This is seen with obesity. d. This is seen with age-related macular degeneration e. This is more common with Maturity onset diabetes of the young (MODY)

NURSINGTB.COM

17. Match each phrase with the most appropriate description. Answers can be used more than once. Transcription factors involved in limb development a. BRCA1 and BRCA2 (breast cancer) gene products b. HOX (homeobox) gene family c. Leptin mutations d. Stargardt's disease mutations e. Glucokinase mutations Answer: b Correct Feedback: b. This is seen in transcription factors involved in limb development Incorrect Feedback: a. This is seen in interactions with the Rad51 DNA repair system c. This is seen with obesity. d. This is seen with age-related macular degeneration e. This is more common with Maturity onset diabetes of the young (MODY) 18. Match each phrase with the most appropriate description. Answers can be used more than once. Maturity onset diabetes of the young (MODY) a. BRCA1 and BRCA2 (breast cancer) gene products

Multiple Choice b. HOX (homeobox) gene family c. Leptin mutations d. Stargardt's disease mutations e. Glucokinase mutations Answer: e Correct Feedback: e. This is common with Maturity onset diabetes of the young (MODY) Incorrect Feedback: a. This is seen in interactions with the Rad51 DNA repair system b. This is seen in transcription factors involved in limb development c. This is seen with obesity. d. This is seen with age-related macular degeneration

Jorde: Medical Genetics, 5th Edition Chapter 8: Gene Mapping and Identification Multiple Choice 1. In one gene mapping technique, denatured DNA from metaphase chromosomes is hybridized with a radioactively labeled probe. This DNA is then exposed to film to reveal the approximate chromosomal location of the DNA in the probe. Which technique does this best describe? a. Southern blotting b. In situ hybridization c. Somatic cell hybridization d. Fluorescence in situ hybridization e. Single strand conformation polymorphism (SSCP) analysis Answer: b Correct Feedback: b. This describes in situ hybridization. Incorrect Feedback: a. Sothern blotting is a laboratory procedure in which DNA fragments that have been electorphoresed through a gel are transferred to a solid membrane, such as nitrocellulose. The DNA can then be hybridized with a labeled probe and exposed to X-ray film. c. Somatic cell hybridization is a physical gene mapping technique in which somatic cells from two different species are fused and allowed to undergo cell division. Chromosomes from one species are selectively lost, resulting in clones with only one or a few chromosomes from one of the species. d. FISH is a molecular cytogenetic technique in which labelled probes are hybridized with chromosomes and then visualized under a fluorescence microscope. e. SSCP is a technique for detecting variation in DNA sequence by running singlestranded DNA fragments through a non-denaturing gel. Fragments with differing secondary structure (conformation) caused by sequence variation will migrate at different rates. 2. Consider the table of LOD scores shown below for an autosomal dominant disease. The first line gives recombination frequencies, and each subsequent line represents the LOD score pattern found for a specific family. What phrase best describes this pattern? q: 0.0 0.1 0.2 0.3 0.4 2.2 1.4 1.0 0.8 0.2 1.5 1.2 1.2 0.6 0.1 2.0 1.0 0.8 0.3 -0.1 1.2 0.8 0.2 0.1 0.1 a. Tight linkage b. Allelic heterogeneity c. Loose linkage

Multiple Choice

d. Linkage disequilibrium e. Locus heterogeneity Answer: a Correct Feedback: This table shows tight linkage. Incorrect Feedback: This is not shown by this table. 3. Suppose you are attempting to find a disease-causing gene, and you have identified a number of families in which the disease is transmitted. If you have no knowledge of the gene product and no reasonable candidate locus, which of the following would be the first technique you would be most likely to use? a. Linkage analysis b. DNA sequencing c. Single strand conformation polymorphism (SSCP) analysis d. Denaturing gradient gel electrophoresis (DGGE) e. Fluorescence in situ hybridization (FISH) Answer: a Correct Feedback: This is the first technique that you would use. Incorrect Feedback: This wouN ldUbR eS usI edNaGftT erBu. siC ngOlM inkage analysis. 4. Now suppose that you do have a reasonable candidate locus for the disease you are studying. Which of the following would be least likely to contribute useful information? a. DNA sequencing b. Single strand conformation polymorphism (SSCP) analysis c. Northern blotting d. Denaturing gradient gel electrophoresis (DGGE) e. Chromosome karyotype Answer: e Correct Feedback: A chromosome karyotype would be useful in chromosomal abnormalities, but not in single gene disorders. Incorrect Feedback: This would be useful. 5. Some autosomal recessive diseases have a high prevalence in large populations, even though they are often fatal (e.g., sickle cell disease in Africans, cystic fibrosis in Europeans). Which of the following is the most likely explanation for this phenomenon? a. Inbreeding b. High mutation rates in specific populations c. Survival advantage in heterozygous carriers

Multiple Choice

d. Survival advantage in individuals who are normal homozygotes e. None of the above mechanisms explain the pattern Answer: c Correct Feedback: This explanation would explain why these diseases are so prevalent. Incorrect Feedback: This does not explain the phenomenon. 6. Which of the following would you not expect to see in a typical multifactorial disorder? a. Positive correlation between prevalence of the disorder in the population and sibling recurrence risk b. Rapid decrease of recurrence risk with more remote degrees of relationship c. Co-occurrence of the disorder in fathers and sons d. Sibling recurrence risk of 50% e. Higher concordance in monozygotic twins than in dizygotic twins Answer: d Correct Feedback: You would not expect to see such a high reccurance risk in a typical multifactorial disorder. Incorrect Feedback: This wouN ldUbR eS seI enNiG nT aB m. ulC tifO acMtorial disorder. 7. You would be likely to observe the lowest heritability score in a. Cystic fibrosis b. Spina bifida c. Cleft lip/palate d. Mumps e. Congenital heart disease Answer: d Correct Feedback: Mumps is an infectios disease not a genetic one. Therefore, mumps would have the lowest heritability score. Incorrect Feedback: There is a genetic component here and thus a higher heritability score. 8. Familial hypercholesterolemia a. Can be caused by defects in receptor-mediated endocytosis b. Is an important cause of inherited heart disease c. Is an example of a disease in which gene therapy is being tested d. A and B only e. A, B, and C

Multiple Choice

Answer: e Correct Feedback: e. All of the answers are true. Incorrect Feedback: a. This is not the only true answer. b. This is not the only true answer. c. This is not the only true answer. d. C is also true. 9. Familial Alzheimer disease is characterized by a. Autosomal dominant transmission in some families b. Locus heterogeneity c. Population association with specific apolipoprotein E alleles d. All of the above e. None of the above Answer: d Correct Feedback: All of the above statements are true. Incorrect Feedback: This is not the only true answer. otU trR ueSoIf N scGhiz op. hC reni a? 10. Which of the following is nN TB OM a. Monozygotic twin concordance exceeds dizygotic twin concordance. b. Gene mapping studies have shown linkage to specific polymorphic markers in some families. c. A specific schizophrenia susceptibility gene has been cloned. d. Adoption data indicate an increased risk of the disorder among the biological offspring of schizophrenic parents when the offspring are reared by normal parents. e. Second-degree relatives of affected individuals have a lower risk of developing the disease than do first-degree relatives. Answer: c Correct Feedback: This statement is not true of schizophrenia. Incorrect Feedback: This is a true statement. 11. Which of the following is an advantage of indirect genetic diagnosis? a. Family data are not needed b. Error due to recombination is not present c. Uninformative matings do not present a problem d. All of the above e. None of the above

Multiple Choice Answer: e Correct Feedback: e. None of these possibilities are correct. Incorrect Feedback: a. This is not true. b. This is not true. c. This is not true. d. None are correct. 12. A neural tube defect (anencephaly or spina bifida) could be detected by a. Anmiocentesis b. Chorionic villus sampling c. Diagnosis of fetal cells in maternal circulation d. In vitro fertilization diagnosis e. All of the above Answer: a Correct Feedback: a. This is the only way to detect neural tube defects of those listed. Incorrect Feedback: b. This does not allow you to detect neural tube defects. c. This does not allow you to detect neural tube defects. d. This does not allow you to detect neural tube defects. e. Only one of the above is true. 13. Which of the following is not currently a candidate for gene therapy? a. Cystic fibrosis b. Adenosine deaminase (ADA) deficiency c. Lung cancer d. Bipolar affective disorder e. AIDS Answer: d Correct Feedback: This is not a candidate currently. Incorrect Feedback: This is a candidate for gene therapy. 14. Match each genetic disease with the most appropriate molecular or biochemical characteristic. Answers can be used more than once. Serine protease inhibitor defect a. Obesity b. Sickle-cell disease c. Familial adenomatous polyposis coli d. Tay-Sachs disease e. Alpha-1 antitrypsin deficiency

Multiple Choice

Answer: e Correct Feedback: e. Alpha-1 antitrypsin deficiency is a Serine protease inhibitor defect. Incorrect Feedback: a. Obesity is associated with Leptin mutations in mouse. b. Sickle cell disease is a specific mutation in beta-globin gene. c. Familial adenomatous polyposis coli is an interaction of gene product with betacatenin. d. Tay-Sachs disease is a hexosaminidase A deficiency. 15. Match each genetic disease with the most appropriate molecular or biochemical characteristic. Answers can be used more than once. Hexosaminidase A deficiency a. Obesity b. Sickle-cell disease c. Familial adenomatous polyposis coli d. Tay-Sachs disease] e. Alpha-1 antitrypsin deficiency Answer: d Correct Feedback: d. Tay-SacN hsUdR isS eaI seNiG s aThBe. xoCsaOmMinidase A deficiency. Incorrect Feedback: a. Obesity is associated with Leptin mutations in mouse. b. Sickle cell disease is a specific mutation in beta-globin gene. c. Familial adenomatous polyposis coli is an interaction of gene product with betacatenin. e. Alpha-1 antitrypsin deficiency is a Serine protease inhibitor defect. 16. Match each genetic disease with the most appropriate molecular or biochemical characteristic. Answers can be used more than once. Leptin mutations in mouse a. Obesity b. Sickle-cell disease c. Familial adenomatous polyposis coli d. Tay-Sachs disease e. Alpha-1 antitrypsin deficiency Answer: a Correct Feedback: a. Obesity is associated with Leptin mutations in mouse.

Incorrect Feedback: b. Sickle cell disease is a specific mutation in beta-globin gene.

Multiple Choice

c. Familial adenomatous polyposis coli is an interaction of gene product with betacatenin. d. Tay-Sachs disease is a hexosaminidase A deficiency. e. Alpha-1 antitrypsin deficiency is a Serine protease inhibitor defect. 17. Match each genetic disease with the most appropriate molecular or biochemical characteristic. Answers can be used more than once. Interaction of gene product with beta-catenin a. Obesity b. Sickle-cell disease c. Familial adenomatous polyposis coli d. Tay-Sachs disease e. Alpha-1 antitrypsin deficiency Answer: c Correct Feedback: c. Familial adenomatous polyposis coli is an interaction of gene product with beta-catenin. Incorrect Feedback: a. Obesity is associated with Leptin mutations in mouse. b. Sickle cell disease is a specific mutation in beta-globin gene. d. Tay-Sachs disease is a hexosaminidase A deficiency. e. Alpha-1 antitrypsin deficiency is a Serine protease inhibitor defect.

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18. Match each genetic disease with the most appropriate molecular or biochemical characteristic. Answers can be used more than once. Specific mutation in beta-globin gene a. Obesity b. Sickle-cell disease c. Familial adenomatous polyposis coli d. Tay-Sachs disease e. Alpha-1 antitrypsin deficiency Answer: b Correct Feedback: b. Sickle cell disease is a specific mutation in beta-globin gene. Incorrect Feedback: a. Obesity is associated with Leptin mutations in mouse. c. Familial adenomatous polyposis coli is an interaction of gene product with betacatenin. d. Tay-Sachs disease is a hexosaminidase A deficiency. e. Alpha-1 antitrypsin deficiency is a Serine protease inhibitor defect. 19. Mosaicism is a frequent cause of survival to term a. Down syndrome b. Trisomy 13

Multiple Choice

c. Trisomy 18 d. Klinefelter syndrome (47,XXY) e. Turner syndrome (45,X) Answer: e Correct Feedback: This is often the case with Turner syndrome. Incorrect Feedback: This is not as likely as it is with Turner syndrome. 20. Leading known genetic cause of mental retardation in the human a. Down syndrome b. Trisomy 13 c. Trisomy 18 d. Klinefelter syndrome (47,XXY) e. Turner syndrome (45,X) Answer: a Correct Feedback: Down syndrome is the leading cause of mental retardation accounting for 10% of all cases of mental retardation in the United States. Incorrect Feedback: This is not as prevelant as Down syndrome.

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21. Phenotype is seen only in males a. Down syndrome b. Trisomy 13 c. Trisomy 18 d. Klinefelter syndrome (47,XXY) e. Turner syndrome (45,X) Answer: d

Correct Feedback: d. This is seen only in males. Incorrect Feedback: a. This is seen in both males and females. b. This is seen in both males and females. c. This is seen in both males and females. e. This is seen only in females. 22. Which of the following can be used as vectors in somatic cell gene therapy? a. Retrovirus b. Liposome c. Adenovirus d. Adeno-associated virus e. All of the above

Multiple Choice

Answer: e Correct Feedback: All of the above can be used as vectors. Incorrect Feedback: This is not the only true answer. 23. Maternal serum alpha-fetoprotein levels can be used to screen for a. Turner syndrome b. Neural tube defects c. Klinefelter syndrome d. Down syndrome e. B and D Answer: e Correct Feedback: e. Both b and d are true. Incorrect Feedback: a. Serum alpha-fetoprotein levels cannot be used to screen for this. b. D is also true. c. Serum alpha-fetoprotein levels cannot be used to screen for this. d. B is also true. otU aR pot enti al T pB ro. blC em with somatic cell gene therapy? 24. Which of the following is nN SI NG OM a. Transient expression b. Potential for oncogenesis as a result of random integration c. Difficulties in regulating gene activity d. Ethical concerns surrounding the permanent alteration of our genetic heritage e. None of the above Answer: d Correct Feedback: d. This would only be a problem in non-somatic cells. Incorrect Feedback: a. This is a potential problem. b. This is a potential problem. c. This is a potential problem. e. There is an answer. 25. Which of the following pertain(s) only to genes located on the same chromosome? a. Linkage b. Synteny c. Linkage disequilibrium d. Association e. A,B, and C

Multiple Choice

Answer: e Correct Feedback: e. A b and c pertain to genes located on the same chromosome. Incorrect Feedback: a. There are other true answers as well. b. There are other true answers as well. c. There are other true answers as well. d. Association is the simultaneous occurrence of two traits or events, more often than expected by chance. This does not necessarily mean that they are on the same chromosome. 26. Multifactorial inheritance can reliably be distinguished from single-gene inheritance by a. Differences in sibling recurrence risks, with single-gene recurrence risks always being higher b. More rapid decline in recurrence risks in more remote relatives for multifactorial diseases c. More pronounced differences in sex ratio for multifactorial diseases d. For multifactorial diseases, sibling recurrence risk increases when there are more affected individuals in the family e. B and D Answer: e Correct Feedback: e. Both b and d are true. Incorrect Feedback: a. Recurrence risk is not always higher in single-gene disorders. b. D is also true. c. This is not seen. d. B is also true. 27. Which of the following is not true about chromosome translocations a. They can lead to missing or duplicated chromosome material in offspring of translocation carriers b. They can be helpful in mapping disease-causing genes c. They can cause cancer when they occur in somatic cells d. They are known to increase with advanced maternal age e. B and D Answer: d Correct Feedback: d. The risk does not increase with maternal age. Incorrect Feedback: a. This is true about translocations. b. This is true about translocations. c. This is true about translocations.

Multiple Choice

e. B is true. 28. Alcoholism a. is known to cluster in families b. is linked to a polymorphism near the dopamine D2 receptor gene c. is seen with increased incidence in the offspring of alcoholic parents, even when they are adopted by non-alcoholic parents d. is seen with increased incidence in the offspring of non-alcoholic parents when they are adopted by alcoholic parents e. A and C Answer: e Correct Feedback: e. Both a and c are true. Incorrect Feedback: a. C is also true. b. This is not true. c. A is also true. d. This is not true.

Jorde: Medical Genetics, 5th Edition Chapter 9: Immunogenetics Multiple Choice 1. Consider the table of LOD scores shown below for an autosomal dominant disease. The first line gives recombination frequencies, and each subsequent line represents the LOD score pattern found for a specific family. What phrase best describes this pattern? q: 0.0 0.1 0.2 0.3 0.4 2.2 1.4 1.0 0.8 0.2 1.5 1.6 1.2 0.6 0.1 -1.8 -1.0 -0.8 -0.3 -0.1 -2.1 -1.7 -1.2 -0.8 -0.3 a. Tight linkage b. Allelic heterogeneity c. Loose linkage d. Linkage disequilibrium e. Locus heterogeneity Answer: e Correct Feedback: This pattern shows locus heterogeneity because it has positive numbers in some families and nN egUaR tivSeI inNoGthTeB rs. . COM Incorrect Feedback: This doesn't describe this pattern. 2. Fluorescence in situ hybridization (FISH) a. does not involve radioactivity b. offers better resolution than standard in situ hybridization c. is sometimes used with interphase chromosomes d. a,b, and c e. a and c Answer: d Correct Feedback: d. All are true. Incorrect Feedback: a. This is not the only true answer. b. This is not the only true answer. c. This is not the only true answer. e. B is true also. 3. Loci that are located on the same chromosome but not necessarily linked are said to be a. in linkage disequilibrium b. associated

Multiple Choice

c. syntenic d. unassociated e. in linkage equilibrium Answer: c Correct Feedback: c. That is the definition of syntenic. Incorrect Feedback: a. Linkage disequilibrium is nonrandom association of alleles at linked loci in populations. b. Association is the simultaneous occurrence of two traits or events, more often than expected by chance. d. Association is the simultaneous occurrence of two traits or events, more often than expected by chance, so unassociation would be when this is not true. e. Linkage equilibrium is the lack of preferential association of alleles at linked loci. 4. Which of the following would be least useful if you were looking for a gene using positional cloning? a. identification of CG islands b. identification of a candidate gene within the region of interest c. identification of a chromosome translocation within the region of interest in a patient d. the finding that some portions of the region of interest are highly conserved among different species r lin locus at a recombination frequency e. finding a polymorphic markeN URked SItoNtGheTdBis.eaCseOM of .10 Answer: e Correct Feedback: This would be the least useful. Incorrect Feedback: This would be useful. 5. Which of the following would not help to distinguish autosomal dominant from autosomal recessive inheritance? a. presence of consanguinity b. proportion of affected offspring in each mating c. sex ratio of affected individuals d. appearance of the disease phenotype in multiple generations of the family e. all of the above Answer: c Correct Feedback: c. Sex ratio does not factor into autosomal conditions. Incorrect Feedback: a. This can help you distinguish. b. This can help you distinguish.

Multiple Choice d. This can help you distinguish. e. There is an answer. 6. Autoimmune diseases a. are sometimes associated with specific MHC class II alleles b. are sometimes associated with specific MHC class I alleles c. may sometimes involve molecular mimicry d. A and C e. A, B, and C Answer: e Correct Feedback: e. All of the above are true. Incorrect Feedback: a. There are other true answers as well. b. There are other true answers as well. c. There are other true answers as well. d. B is also true. 7. Which of the following is not involved in generating antibody diversity? a. a high rate of germline mutation b. junctional diversity c. somatic recombination d. a high rate of somatic mutatioNnURSINGTB.COM e. multiple copies of V, J, and D genes in the germline Answer: a Correct Feedback: Its somatic mutation not germline that is involved. Incorrect Feedback: This is involved. 8. There is very good evidence that many neural tube defects can be prevented by a. chorionic villus sampling to diagnose the disorder b. in vitro fertilization diagnosis to diagnose the disorder c. folic acid supplementation d. sulfuric acid supplementation e. gene therapy Answer: c Correct Feedback: Folic acid supplementation has been shown to reduce neural tube defects. Incorrect Feedback: This has not been shown.

Multiple Choice 9. Which of the following is true of obesity? a. It can be caused by leptin receptor mutations in humans. b. It can be caused by mutations in the leptin gene in humans. c. No specific obesity genes have been identified in the human. d. It is rare in North America. e. It is often associated with type I diabetes. Answer: a Correct Feedback: a. This has been shown to cause obesity. Incorrect Feedback: b. This has not been shown to be true. c. Some genes have been found (the leptin gene and its receptor) d. Obesity is not rare in North America. e. It is a risk factor for Type II diabetes. 10. Which of the following does not differ in type I and type II diabetes a. average age of onset b. presence of insulin resistance c. presence of autoimmunity d. degree of insulin production e. presence of elevated blood sugar Answer: e Correct Feedback: e. The blood sugar is elevated in both type I and type II diabetes. Incorrect Feedback: a. This is different. The average age of onset is earlier for type I diabetes. b. This is not true. c. Only type I is an autoimmune disease. d. This is not true. 11. In genetic screening, sensitivity refers to a. the proportion of true negatives detected by the test b. the proportion of true positives detected by the test c. the demonstration of a compassionate attitude d. the positive predictive value of the test e. none of the above Answer: b Correct Feedback: b. Sensitivity is the proportion of affected individuals who are correctly identified by a test. Incorrect Feedback: a. This is specificity.

Multiple Choice

c. This is not true in terms of genetic screening. d. This is another term altogether. e. One of the above is true. 12. Match each disorder with the most appropriate characteristic. Answers can be used more than once. chloride ion channel defect a. Marfan syndrome b. Tay-Sachs disease c. Cystic fibrosis d. Sickle cell disease e. Osteogenesis imperfecta Answer: c Correct Feedback: c. Cystic fibrosis is a chloride ion channel defect. Incorrect Feedback: a. Marfan syndrome is associated with fibrillin mutations. b. Tay-Sachs disease is associated with a high gene frequency among Ashkenazi Jews. d. Sickle cell disease is associated with recurrent infections, vaso-occlusive crises leading to tissue infarctions. e. Osteogenesis imperfecta is associated with type I collagen mutations. eU mR ostSI appr ia. teCcha 13. Match each disorder with thN NGopr TB OMracteristic. Answers can be used more than once. gene frequency is especially high among Ashkenazi Jews a. Marfan syndrome b. Tay-Sachs disease c. Cystic fibrosis d. Sickle cell disease e. Osteogenesis imperfecta Answer: b Correct Feedback: b. Tay-Sachs disease is associated with a high gene frequency among Ashkenazi Jews. Incorrect Feedback: a. Marfan syndrome is associated with fibrillin mutations. c. Cystic fibrosis is a chloride ion channel defect. d. Sickle cell disease is associated with recurrent infections, vaso-occlusive crises leading to tissue infarctions. e. Osteogenesis imperfecta is associated with type I collagen mutations. 14. Match each disorder with the most appropriate characteristic. Answers can be used more than once. sodium channel defect

Multiple Choice

a. Marfan syndrome b. Tay-Sachs disease c. Cystic fibrosis d. Sickle cell disease e. Osteogenesis imperfecta Answer: c Correct Feedback: c. Cystic fibrosis is a chloride ion channel defect. Incorrect Feedback: a. Marfan syndrome is associated with fibrillin mutations. b. Tay-Sachs disease is associated with a high gene frequency among Ashkenazi Jews. d. Sickle cell disease is associated with recurrent infections, vaso-occlusive crises leading to tissue infarctions. e. Osteogenesis imperfecta is associated with type I collagen mutations. 15. Match each disorder with the most appropriate characteristic. Answers can be used more than once. type I collagen mutations a. Marfan syndrome b. Tay-Sachs disease c. Cystic fibrosis d. Sickle cell disease e. Osteogenesis imperfecta Answer: e Correct Feedback: e. Osteogenesis imperfecta is associated with type I collagen mutations. Incorrect Feedback: a. Marfan syndrome is associated with fibrillin mutations. b. Tay-Sachs disease is associated with a high gene frequency among Ashkenazi Jews. c. Cystic fibrosis is a chloride ion channel defect. d. Sickle cell disease is associated with recurrent infections, vaso-occlusive crises leading to tissue infarctions. 16. Match each disorder with the most appropriate characteristic. Answers can be used more than once. fibrillin mutations a. Marfan syndrome b. Tay-Sachs disease c. Cystic fibrosis d. Sickle cell disease e. Osteogenesis imperfecta Answer: a

Multiple Choice

Correct Feedback: a. Marfan syndrome is associated with fibrillin mutations. Incorrect Feedback: b. Tay-Sachs disease is associated with a high gene frequency among Ashkenazi Jews. c. Cystic fibrosis is a chloride ion channel defect. d. Sickle cell disease is associated with recurrent infections, vaso-occlusive crises leading to tissue infarctions. e. Osteogenesis imperfecta is associated with type I collagen mutations. 17. Match each disorder with the most appropriate characteristic. Answers can be used more than once. recurrent infections, vaso-occlusive crises leading to tissue infarctions a. Marfan syndrome b. Tay-Sachs disease c. Cystic fibrosis d. Sickle cell disease e. Osteogenesis imperfecta Answer: d Correct Feedback: d. Sickle cell disease is associated with recurrent infections, vasoocclusive crises leading to tissue infarctions.

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Incorrect Feedback: a. Marfan syndrome is associated with fibrillin mutations. b. Tay-Sachs disease is associated with a high gene frequency among Ashkenazi Jews. c. Cystic fibrosis is a chloride ion channel defect. e. Osteogenesis imperfecta is associated with type I collagen mutations. 18. Match each type of receptor with the most appropriate characteristic. Cytotoxic T lymphocyte receptors a. Interact with peptides bound to class II MHC molecules b. Interact with peptides bound to class I MHC molecules c. Have uniform amino acid sequences in all cells of the individual d. Are secreted from the cell into the circulation e. Have recently been shown to be sensitive to insulin Answer: b Correct Feedback: b. Cytotoxic T lymphocyte receptors interact with peptides bound to class I MHC molecules. Incorrect Feedback: a. Cytotoxic T lymphocyte receptors interact with peptides bound to class I MHC molecules, not class II. c. This is not true. d. This does not happen

Multiple Choice

e. This is not true. 19. Match each type of receptor with the most appropriate characteristic. Helper T lymphocyte receptors a. Interact with peptides bound to class II MHC molecules b. Interact with peptides bound to class I MHC molecules c. Have uniform amino acid sequences in all cells of the individual d. Are secreted from the cell into the circulation e. Have recently been shown to be sensitive to insulin Answer: a Correct Feedback: a. Helper T lymphocyte receptors interact with peptides bound to class II MHC molecules. Incorrect Feedback: b. They interact with peptides bound to class II MHC moleculed not class I. c. This is not true. d. This is not true. e. This is not true. 20. Match each type of receptor with the most appropriate characteristic. Helper T lymphocyte receptors a. Interact with peptides bound N toU clR ass ules .oClec SIIINMGHC TBm OM b. Interact with peptides bound to class I MHC molecules c. Have uniform amino acid sequences in all cells of the individual d. Are secreted from the cell into the circulation e. A and D Answer: e Correct Feedback: B lymphocyte receptors have recently been shown to be sensitive to insulin. Incorrect Feedback: This is not true. 21. Which of the following is (are) an example(s) of a sex-influenced trait? a. Autosomal dominant breast cancer b. Adenomatous polyposis coli c. Male-pattern baldness d. Cystic fibrosis e. A and C Answer: e Correct Feedback: e. Both a and c are examples of sex-influenced traits.

Multiple Choice

Incorrect Feedback: a. C is also an example. b. This is not an example. c. A is also an example. d. This is not an example. 22. The quantitative trait locus approach typically involves all of the following except a. the use of a high-resolution genetic map b. backcross matings in experimental animals c. the identification of sequence homology between humans and experimental animals d. somatic cell hybridization e. B and D Answer: d Correct Feedback: d. Somatic cell hybridization is not involved in the quantitative trait locus approach. Incorrect Feedback: a. This is involved. b. This is involved. c. This is involved. e. B is involved. 23. An increased risk of Down syndrome in a couple's offspring can be caused by a. advanced maternal age b. germline mosaicism for trisomy 21 in a normal mother c. father is a carrier of a 14/21 Robertsonian translocation d. mother is a carrier of a 14/21 reciprocal translocation involving the distal third of chromosome 21 e. all of the above Answer: e Correct Feedback: All of the above can increase the risk for Down syndrome. Incorrect Feedback: This is not the only true answer.

24. Which of the following can be used to help provide a prenatal diagnosis of Down syndrome? a. Chorionic villus sampling b. Diagnosis of fetal cells in mother's circulation c. Amniocentesis d. Maternal serum alpha-fetoprotein screening e. all of the above Answer: e

Multiple Choice

Correct Feedback: All of the above can be used. Incorrect Feedback: This is not the only true answer. 25. Somatic cell gene therapy is feasible for which of the following diseases? a. spina bifida b. cystic fibrosis c. alcoholism d. adenosine deaminase (ADA) deficiency e. B and D Answer: e Correct Feedback: e. Somatic cell therapy has been tried in both of these disorders. Incorrect Feedback: a. Somatic cell therapy would not be feasible for this disease. b. D is also correct. c. Somatic cell therapy would not be feasible for this disease. d. B is also correct. 26. Which of the following are advantages of direct genetic diagnosis over indirect genetic diagnosis? a. Recombination does not causN eU diR agn ostic rsCOM SI NGerr TBo. b. PCR techniques can be used c. Information from other family members is not needed d. Direct diagnosis can be performed in the prenatal period e. A and C Answer: e Correct Feedback: e. Both a and c are true. Incorrect Feedback: a. C is also true. b. This is not true. c. A is also true. d. This is not true. 27. Autosomal dominant breast cancer caused by mutations in the BRCA1 gene (chromosome 17) is characterized by: a. relatively early age of onset of the disease b. increased incidence of breast cancer in males c. increased risk of ovarian cancer d. increased risk of small cell lung cancer e. A and C

Multiple Choice Answer: e Correct Feedback: e. Both a and c are true. Incorrect Feedback: a. C is also true. b. This is not true. c. A is also true. d. This is not true.

Jorde: Medical Genetics, 5th Edition Chapter 10: Developmental Genetics Multiple Choice 1. Thus far, two genes have been found that can cause autosomal dominant breast cancer (one on chromosome 13 and one on chromosome 17). This is best described as an example of: a. Linkage b. Allelic heterogeneity c. Synteny d. Linkage disequilibrium e. Locus heterogeneity Answer: e Correct Feedback: e. This is an example of locus heterogeneity. Incorrect Feedback: a. This is not an example of linkage. b. This is not an example of allelic heterogeneity. c. This is not an example of synteny. d. This is not an example of linkage disequilibrium. 2. The in situ hybridization technique does not involve the use of a. Cloned probes b. X-ray film c. Complementary base pairing d. Gene product expression e. Metaphase chromosomes Answer: d Correct Feedback: In-situ hybridization does not involve gene product expression. Incorrect Feedback: In-situ hybridization does involve this. 3. The Utah Mormons have been the subjects of numerous genetic studies. Which of the following is not true of this population? a. Inbreeding rates are low b. The prevalence rates of PKU and cystic fibrosis are high, relative to other Caucasian populations c. Inbreeding rates have declined through time d. Genetically, the population still resembles populations derived from northern Europe e. Some cases of multiple consanguinity have been observed

Multiple Choice

Answer: b Correct Feedback: This is not true of the Utah Mormons. Incorrect Feedback: This is true of the Utah Mormons. 4. Which of the following is not true of linkage disequilibrium? a. It is a type of association that involves alleles at linked loci b. It can be caused by natural selection c. It can be caused by a disease mutation that has arisen recently on a chromosome containing a specific marker allele d. It becomes nondetectable after one generation of random mating e. It can be used to map genes Answer: d Correct Feedback: This is not true. Incorrect Feedback: This is true. 5. For which of the following diseases would you expect to observe the highest heritability a. Neural tube defects b. Measles c. Cleft lip/palate d. Schizophrenia e. Cystic fibrosis Answer: e Correct Feedback: This disease would be expected to have the highest heritability. Incorrect Feedback: This disease has non-heritable aspects to it. 6. The quantitative trait locus method does not typically involve a. Estimation of heritability b. Linkage analysis c. DNA sequence homology between humans and animal models d. Breeding experiments e. Gene cloning Answer: a Correct Feedback: The quantitative trait locus method does not involve estimations of heritability.

Multiple Choice

Incorrect Feedback: It does involve this. 7. Which of the following is least likely to be seen in highly heritable subsets of multifactorial diseases? a. Early age of onset b. Relatively severe presentation of the disorder c. Recurrence risk is higher in siblings of probands than in more remote relatives d. Bilateral presentation (when there is laterality) e. Recurrence risk in siblings is higher when the proband is affected later in life Answer: e Correct Feedback: The opposit is true. Recurrence risk in siblings is higher when the proband is affected earlier in life Incorrect Feedback: This is seen in heritable subsets of multifactorial diseases. 8. A multifactorial disease has a prevalence of 1/500 in females and 1/1,000 in males. You are evaluating families in which a parent is affected. Under a sex-specific threshold model, which parent-offspring combination would you expect to yield the highest risk for the offspring? a. Father-son b. Father-daughter c. Mother-son d. Mother-daughter e. A and B are equal Answer: b Correct Feedback: b. This combination would give you the highest risk because it paires the less commonly affected parent sex with the more commonly affected child sex. Incorrect Feedback: a. The risk would not be as high here. c. The risk would not be as high here. d. The risk would not be as high here. e. B is more likely than A. 9. Which of the following are not part of the adaptive immune system? a. T-cell receptors b. Immunoglobulins c. Natural Killer cells d. MHC class I molecules e. MHC class II molecules Answer: c

Multiple Choice

Correct Feedback: These are part of the innate immune system. Incorrect Feedback: These are part of the adaptive immune system. 10. Which of the following characteristics are not shared by T-cell receptors and B-cell receptors? a. Multiple germline genes that can encode the joining region b. Junctional diversity c. Somatic recombination d. Multiple germline genes that can encode the variable region e. Secretion from the cell surface into the systemic circulation Answer: e Correct Feedback: This is only true of B-cell receptors. Incorrect Feedback: This is true of both B- and T-cell receptor. 11. Which of the following factors are not part of the regulatory process that helps to prevent uncontrolled cell growth leading to cancer? a. Signal transduction molecules b. Growth factors c. Growth factor receptors d. Nuclear transcription factors N UR SI NG TB.COM e. DNA polymerase Answer: e Correct Feedback: This is a normal cell component that does not affect tumor growth. Incorrect Feedback: These are part of the regulatory process. 12. A large proportion of the mutations leading to adenomatous polyposis coli (APC) are a. Missense mutations b. Nonsense mutations c. Splice site mutations d. In-frame deletions e. Expanded trinucleotide repeats Answer: b Correct Feedback: Most APC mutations are nonsense or frameshift mutations that yield a truncated protein product. Incorrect Feedback: This is not as common with APC mutations.

Multiple Choice

13. Which of the following offers a long-term (> 1 year or so) gene therapy treatment? a. Retroviral vectors inserted into bone marrow stem cells b. Adenovirus vectors c. Retroviral vectors inserted into peripheral lymphocytes d. All of the above e. None of the above Answer: a Correct Feedback: a. This offers long-term treatment because the cells are multipotent Incorrect Feedback: b. This is not as likely to be long lasting because the affected cells have a limited life span. c. This is not as likely to be long lasting because the affected cells have a limited life span. d. Only one of the above is true. e. One of the above is true. 14. Which of the following is not true of genetic diagnosis using a linked marker? a. The location of the disease gene does not need to be known b. Family members must be studied c. Uninformative matings are sometimes a problem d. Crossover events may reduce the accuracy of diagnosis ere um e. Becomes impractical when thN .bCerOoMf different disease-causing URisSaIlarg NGeTnB mutations at a locus. Answer: e Correct Feedback: This is not a problem. Incorrect Feedback: This is true of using a linked marker. 15. Which of the following systems would be most important in determining maternalfetal compatibility? a. Rh blood group b. ABO blood group c. MHC class I molecules d. MHC class II molecules e. MHC class III molecules Answer: a Correct Feedback: Maternal-fetal Rh incompatibility can produce hemolytic disease of the newborn. Incorrect Feedback: This is not the most important factor.

Multiple Choice

16. Down syndrome a. Lysosomal storage disorder b. Elevated amniotic alpha-fetoprotein c. Decreased amniotic alpha-fetoprotein d. Vocal and motor tics e. Rhodopsin mutations Answer: c Correct Feedback: This is a diagnostic test for Down syndrome. Incorrect Feedback: This is not associated with Down syndrome. 17. Tourette syndrome a. Lysosomal storage disorder b. Elevated amniotic alpha-fetoprotein c. Decreased amniotic alpha-fetoprotein d. Vocal and motor tics e. Rhodopsin mutations Answer: d Correct Feedback: This is assoNcU iaR tedSw ur. etC teOsM yndrome. IiNthGTToB Incorrect Feedback: This is not associated with Tourette syndrome. 18. Spina bifida a. Lysosomal storage disorder b. Elevated amniotic alpha-fetoprotein c. Decreased amniotic alpha-fetoprotein d. Vocal and motor tics e. Rhodopsin mutations Answer: b Correct Feedback: This is an indicator for spina bifida. Incorrect Feedback: This is not associated with spina bifida. 19. Retinitis pigmentosa a. Lysosomal storage disorder b. Elevated amniotic alpha-fetoprotein c. Decreased amniotic alpha-fetoprotein d. Vocal and motor tics e. Rhodopsin mutations

Multiple Choice

Answer: e Correct Feedback: This causes retinitis pigmentosa. Incorrect Feedback: This is not associated with retinitis pigmentosa. 20. Tay-Sachs disease a. Lysosomal storage disorder b. Elevated amniotic alpha-fetoprotein c. Decreased amniotic alpha-fetoprotein d. Vocal and motor tics e. Rhodopsin mutations Answer: a Correct Feedback: Tay-Sachs disease is a lysosomal storage disease. Incorrect Feedback: This is not associated with Tay-Sachs disease. 21. Anencephaly can be diagnosed by a. Chorionic villus sampling b. Amniocentesis c. In vitro fertilization diagnosisNU RS INGTB.COM d. Ultrasonography e. B and D Answer: e Correct Feedback: e. Both B and D can diagnose anencephaly. Incorrect Feedback: a. This is not useful in diagnosing anencephaly. b. This is not the only true answer. c. This is not useful in diagnosing anencephaly. d. This is not the only true answer. 22. Variations in the angiotensinogen gene are associated with pre-eclampsia. Which of the following is not explained by this statement? a. Angiotensinogen mutations can cause pre-eclampsia b. The angiotensinogen gene is in linkage disequilibrium with a gene that causes preeclampsia c. The angiotensinogen gene may be part of the genetic "background" that causes preeclampsia d. The fetal genotype, not the maternal genotype, is predictive of pre-eclampsia e. B and D

Multiple Choice Answer: d Correct Feedback: d. This is not explained by this statement. Incorrect Feedback: a. This is explained by this statement. b. This is explained by this statement. c. This is explained by this statement. e. B is not correct. 23. The PCR technique involves the use of a. Synthesized oligonucleotide primers b. Cloned probes c. DNA polymerase d. Metaphase chromosomes e. A and C Answer: e Correct Feedback: e. These are both true. Incorrect Feedback: a. This is not the only true answer. b. This is not used in PCR. c. This is not the only true answer. d. This is not used in PCR. 24. Which of the following will not cause triploidy a. Fusion of an egg and polar body with subsequent fertilization by sperm cell b. Meiotic failure, producing diploid sperm or egg c. Dispermy d. Mitotic failure in the early embryo e. B and D Answer: d Correct Feedback: d. This will not cause triploidy. Incorrect Feedback: a. This will cause triploidy. b. This will cause triploidy. c. This will cause triploidy. e. D will not cause triploidy. 25. Which of the following can be used to determine the physical locations of genes? a. Radioactive in situ hybridization b. Fluorescence in situ hybridization c. Somatic cell hybridization d. Cytogenetic analysis of deletions and translocations

Multiple Choice

e. All of the above Answer: e Correct Feedback: e. All of the above can determine the physical location of genes. Incorrect Feedback: a. This is not the only true answer. b. This is not the only true answer. c. This is not the only true answer. d. This is not the only true answer. 26. Which of the following is not true about class I and class II MHC molecules? a. Both present foreign antigens to T-cell receptors b. Both undergo somatic recombination to produce diversity c. Are both encoded by highly polymorphic genes d. Are both located on the surfaces of all nucleated cells e. B and D Answer: e Correct Feedback: e. B and D are both not true. Incorrect Feedback: a. This is true. b. D in incorrect as well. c. This is true. d. B is incorrect as well. 27. Which of the following represent advantages of chorionic villus sampling (CVS) over amniocentesis? a. Placental mosaicism is less common in CVS b. CVS detects a larger range of genetic disorders than does amniocentesis c. CVS has a lower fetal loss rate d. CVS can be performed earlier in the pregnancy e. B and D Answer: d Correct Feedback: d. This is the advantage of CVS. Incorrect Feedback: a. This is not true. b. This is not true. c. This is not true. e. Only D is true. 28. Difficulties encountered in somatic cell gene therapy using retroviral vectors include all of the following except

Multiple Choice

a. Inability to infect nondividing cells b. Limitation on the size of the inserted gene (<i><</i> 8 kb) c. Transient and low-level gene expression d. Inability to integrate into the host's DNA e. C and D Answer: d Correct Feedback: d. They do integrate into the DNA. Incorrect Feedback: a. This is a difficulty. b. This is a difficulty. c. This is a difficulty. e. Only D is not a difficulty. 29. Disadvantages of using allele-specific oligonucleotides for genetic diagnosis include: a. Part of the gene's DNA sequence must be known b. Other family members affected with the disorder must also be studied c. A different oligonucleotide must be used for each disease-causing mutation d. The mutation must occur at a restriction site e. A and C Answer: e Correct Feedback: e. Both A and C are disadvantages. Incorrect Feedback: a. C is also correct. b. This is not a disadvantage. c. A is also correct. d. This is not a disadvantage. 30. The quantitative trait locus technique has been used in attempts to find genes for all of the following except a. Diabetes b. Obesity c. Hypertension d. Schizophrenia e. A and C Answer: d Correct Feedback: d. This is harder because the quantitative trait locus technique requires an animal model. Incorrect Feedback: a. They have looked at this. b. They have looked at this.

Multiple Choice c. They have looked at this. e. Neither A nor C is correct.

Jorde: Medical Genetics, 5th Edition Chapter 11: Cancer Genetics Multiple Choice 1. A LOD score of zero for a recombination frequency of 0.1 indicates a. There is no recombination between the disease locus and a marker locus b. Linkage and non-linkage are equally likely c. Non-likage is more likely than linkage d. Linkage is more likely than non-linkage, but only slightly e. There is loose linkage between the marker and the disease locus Answer: b 2. In a pair of monozygotic twins, one has developed three retinoblastomas during childhood, while the other has developed none. What is the most likely explanation for this? a. locus heterogeneity b. Allelic heterogeneity c. A new mutation has occurred in the unaffected twin, reversing the phenotype d. Variable expression of the phenotype e. Incomplete penetrance Answer: e 3. The exon trapping technique is used a. to identify coding sequence within a DNA sequence. b. to provide new primers for a PCR reaction c. to identify promoter regions of genes d. to test for cross-species conservation of DNA sequence. e. to provide probes for Northern blot analysis Answer: a 4. A 32-bp deletion in the CCR5 gene (also known as CMKBR5) confers almost complete immunity to HIV infection. This gene encodes a. a protease that inhibits HIV replication. b. a cytokine receptor that HIV uses to enter T cells c. a lipoprotein receptor that HIV uses to exit infected T cells. d. an immunoglobulin variant that has high affinity for HIV when the deletion is present e. A T cell receptor that has high affinity for HIV antigen when the deletion is present Answer: b 5. Members of the PAX gene family encode

Multiple Choice a. growth factor receptors b. growth factors involved in embryonic development c. signal transduction molecules important in embryonic development d. enhancers that upregulate developmental genes e. transcription factors Answer: e 6. Which of the following is not true of HOX genes? a. They exist in four major clusters on four different chromosomes in humans. b. A mutation in one of them causes synpolydactyly. c. They contain a DNA sequence that encodes a DNA-binding homeodomain. d. These genes are found only in humans, apes, and monkeys. e. They are important in formation of the anterior/posterior axis in the embryo Answer: d 7. Which of the following is not true of spina bifida? a. It is usually accompanied by secondary hydrocephalus. *b. it can be diagnosed by PCR analysis of fetal cells taken from amniotic fluid. c. it is considered to be a multifactorial disease. d. At least half of spina bifida cases can be prevented by dietary folic acid supplementation. feN ctGinTnBe. urC alOtuMbe closure. e. like anencephaly, it results froNmUaRdSeI Answer: b 8. The gene that causes adenomatous polyposis coli, an autosomal dominant form of colon cancer, is an example of a. a tumor suppressor gene b. an oncogene c. a proto-oncogene d. a DNA repair gene e. a gene that affects telomere shortening in dividing cells Answer: a 9. Which of the following would be most likely to produce a pedigree in which there is only one affected individual with no previous family history of the genetic disorder? a. Autosomal dominant disease with 80% penetrance b. Autosomal recessive disease c. Germline mosaicism for an autosomal dominant disease d. New mutation for an autosomal dominant disease e. X-linked recessive disease Answer: d

Multiple Choice

10. Match the type of disease with the most appropriate type of gene therapy: Autosomal recessive enzyme deficiency that affects nondividing cells a. Antisense therapy b. Retroviral gene replacement therapy c. Germline therapy d. Adenoviral gene replacement therapy e. Germline enhancement therapy Answer: d 11. Match the type of disease with the most appropriate type of gene therapy: Autosomal resessive enzyme deficiency that affects actively dividing cells a. Antisense therapy b. Retroviral gene replacement therapy c. Germline therapy d. Adenoviral gene replacement therapy e. Germline enhancement therapy Answer: b 12. Match the type of disease with the most appropriate type of gene therapy: Gain-of-function mutation a. Antisense therapy b. Retroviral gene replacement therapy c. Germline therapy d. Adenoviral gene replacement therapy e. Germline enhancement therapy Answer: a 13. Which of the following characterize trisomy 21, trisomy 18, and trisomy 13? a. Increase risk with advanced maternal age b. Hypotonia(decreased muscle tone) c. Mental retardation d. Increased risk with advanced paternal age e. a and c Answer: e 14. Which of the follwing types of cancers is (are) known to contain a highly heritable subset of cases characterized by relatively early age of onset? a. breast cancer b. lung cancer c. colon cancer d. bladder cancer

Multiple Choice e. a and c Answer: e 15. Examples of current gene therapy protocols include a. Adenovirus therapy for cystic fibrosis b. Insertion of vascular endothelial growth factor (VEGF) genew into heart muscle to induce blood vessel formation c. retrovirus therapy for adenosine deaminase (ADA) deficiency d. Lung cancer treatment by insertion of normal p53 genes into tumor cells e. All of the above Answer: e 16. Oncogene Mutations a. can affect genes encoding growth factors, growth factor receptors, and signal transduction molecules b. are usually dominant at the cellular level c. often produce a gain of function d. are seen in retinoblastoma and autosomal dominant breast cancer e. a, b, and c Answer: e 17. T-cell receptor genes a. Undergo somatic hypermutation to generate diversity b. undergo somatic recombination to generate diversity c. encode molecules that mature to become antibodies d. exist in multiple copies and are members of a gene family e. b and d Answer: e 18. Positional cloning of a disease gene can involve a. testing for cross-species conservation of DNA sequences b. computer analysis of DNA sequences to test for patterns that signal the presence of a gene c. identification of unmethylated CG "islands" d. screening for mutations in a DNA sequence e. All of the above Answer: e

Jorde: Medical Genetics, 5th Edition Chapter 12: Multifactorial Inheritance and Common Diseases Multiple Choice 1. Match the following disease with the most appropriate description: Waardenburg syndrome a. Contiguous gene/microdeletion syndrome b. Maternal-fetal Rh incompatibility c. PAX transcription-factor mutations d. Mutations affecting protein cleavage and processing e. Fibroblast growth factor receptor mutations Answer: c 2. Match the following disease with the most appropriate description: Alzheimer disease a. Contiguous gene/microdeletion syndrome b. Maternal-fetal Rh incompatibility c. PAX transcription-factor mutations d. Mutations affecting protein cleavage and processing e. Fibroblast growth factor receptor mutations Answer: d 3. Match the following disease with the most appropriate description: Prader-Willi syndrome a. Contiguous gene/microdeletion syndrome b. Maternal-fetal Rh incompatibility c. PAX transcription-factor mutations d. Mutations affecting protein cleavage and processing e. Fibroblast growth factor receptor mutations Answer: a 4. Match the following disease with the most appropriate description: Erythroblastosis fetalis a. Contiguous gene/microdeletion syndrome b. Maternal-fetal Rh incompatibility c. PAX transcription-factor mutations d. Mutations affecting protein cleavage and processing e. Fibroblast growth factor receptor mutations Answer: b

Multiple Choice

5. Which of the following is most likely to be useful in the prenatal diagnosis of a neural tube defect? a. In vitro fertilization diagnosis b. Polar body diagnosis c. Chroionic villus sampling d. Amniocentesis e. Ultrasound Answer: d 6. In which of the following situations would indirect genetic diagnosis be preferred over direct genetic diagnosis? a. Nearly all cases of disease are caused by a single mutation b. Family data are not available c. High rate of new, unique mutations at the disease-causing locus d. High degree of locus heterogeneity e. Highly variable expression of the disease Answer: c 7. Which of the following is not true of familial adenomatous polyposis coli (APC)? a. It is caused by mutations in mismatch repair genes b. Mutations in the APC gene are seen in most colon cancers runc ot. eiC n pr oduct c. Most APC mutations result inNaUtR SIated NGpr TB OM d. Most colon cancers are not caused by inherited APC mutations e. The gene product can modulate Beta-catenin, a cell adhesion molecule Answer: a 8. Which of the following is least likely to be seen in a multifactorial disease? a. Strong correlation between sibling recurrence risk and the population prevalence of the disease b. Negative family history c. Sex-specific threshold effect d. 50% sibling recurrence risk e. Correlation between severity of disease in a proband and sibling recurrence risk Answer: d 9. For which of the following diseases has genetic screening (at the population level) been most effective? a. Sickle-cell disease b. Cystic fibrosis c. Tay-Sachs disease d. Hemochromatosis e. alpha 1-antitrypsin deficiency

Multiple Choice

Answer: c 10. Which of the following techniques is the best example of a population screening procedure? a. Amniocentesis b. Maternal serum alpha-fetoprotein testing c. Chorionic villus sampling d. In vitro fertilization diagnosis e. Percutaneous umbilical blood sampling (PUBS) Answer: b 11. Familial hypercholesterolemia a. can be caused by mutations in the LDL receptor gene b. is more severe in homozygotes than in heterozygotes c. is a subject of somatic cell gene therapy trials d. sometimes causes xanthomas e. all of the above Answer: e 12. Cytotoxic ("killer") T lymphocytes a. Destroy cells that are infected by a pathogen eign b. have receptors that recognizeNfor UR SIant NGigen TBb.oCund OMby class II MHC molecules c. Undergo VDJ recombination d. Undergo somatic hypermutation e. A and C Answer: e 13. B lymphocytes a. Undergo VDJ recombination b. Undergo somatic hypermutation c. Produce circulating antibodies d. Mature in the thymus e. A, B, and C Answer: e 14. As gene therapy vectors, adenoviruses have the following advantages over retroviruses: a. They are less likely to produce an immune response b. They can insert DNA into cells that are not actively dividing c. They will insert DNA that is integrated into the genome and thus will be transmitted to daughter cells d. They can accept a larger DNA insert

Multiple Choice e. B and D Answer: e 15. Mutations in tumor suppressor genes a. Typically produce a loss of function b. can be seen in both inherited and sporadic cancers c. are typically recessive at the cellular level d. are sometimes detected as a loss of heterozygosity e. All of the above Answer: e 16. Which of the following are difficulties associated with somatic cell gene therapy? a. Microinjection produces a high rate of embryonic lethality b. Gain-of-function mutations cannot be corrected c. Ethical concerns with modifying our genetic heritage d. Low or transient levels of gene expression e. a, b, and c Answer: d