Đề thi môn sinh học được cho dưới dạng tiếng anh và được giải chi tiết bằng tiếng anh.
Trang 13 6-mercaptopurine has been used successfullly to treat acute lymphocytic leukemia and inflammatory
diseases, like Crohn's syndrome However, 1 in 300 individuals have a toxic reaction There has been signficant discussion about getting the FDA to require appropriate labeling Why is that?
A 6-mercaptopurine taken with certain foods is toxic
B Individuals with sickle cell anemia cannot take 6-mercaptopurine
C Patients with homozygous mutations in the TPMT gene have a toxic reaction to
6-mercaptopurine
4 A patient is found to have a mutation for HNPCC, hereditary non-polyposis colon cancer and based on
his pedigree, it is inherited, i.e it is found in other family members How do you counsel him to deal with his genetic disease?
A Encourage him to tell his family
B Contact all of his first degree relatives and advise them to be tested
C Treat the disease and forget about the genetics
Problems Section 2
1 How would the genetic content of the somatic cells of individual A, who is the product of a meiotic
nondisjunctional event, differ from that of B, who experienced a mitotic error early in development? Avoid
consideration of exceptional cases
a A’s cells would be genetically heterogeneous; B’s cells would be genetically homogeneous.
b A’s cells would be genetically homogeneous; B’s cells would be genetically heterogeneous.
c A’s and B’s cells would be genetically heterogeneous.
d A’s and B’s cells would be genetically homogeneous.
2 How may these patients differ clinically, assuming the same autosome is involved in each case?
a A and B would develop clinical symptoms of similar intensity.
b A would be clinically affected, but B would be normal.
c A would be clinically affected The degree of abnormality in B would depend upon the proportion of
aneuploid cells present
d B would be clinically affected, but A would be normal.
Trang 23 A man and woman have a daughter with Turner syndrome (45,X) The glucose-6-phosphate dehydrogenasegenotypes of this family are:
Father: G6PD A Mother: G6PD B G6PD B Daughter: G6PD A
G6PD is X-linked During which stage(s) of meiosis could nondisjunction have occurred?
4 Two of the following techniques have proven useful in accurately identifying each chromosome Select the appropriate methods
a Autoradiography
b G-banding
d C-banding
5 Schematically outline meiosis in a male using one pair of autosomal alleles (A and a) and the sex
chromosomes (X and Y) If a encodes an abnormal protein, predict the proportion of normal and anomalous gametes
b ¼ A,X; ¼ a,X; ¼ A,Y; ¼ a,Y d ¼ A,X; ¼ a,X; ½ A,Y
6 A female infant has trisomy (triplication) of chromosome 10 How would you express her karyotype
according to standard nomenclature? Assume there are no other abnormalities in her karyotype
7 Anaphase lag refers to loss of a chromosome during meiosis or mitosis due to failure to migrate to the proper
pole of the dividing cell Which of the following children most likely originated following mitotic anaphase lag? Semicolons separate karyotypes of different cell lines
Trang 38.You have received a report from a clinical cytogenetics lab stating that one of your patients has the karyotype: 46,XX,del(18)(q12) What does this mean?
a Male with a deletion of the short arm of 18 distal to band 12
b Female with a deletion of the short arm of 18 distal to band 12
c Male with a deletion of the long arm of 18 distal to band 12
d Female with a deletion of the long arm of 18 distal to band 12
9 If this patient was fertile, how would you counsel the patient relevant to future children? Assume that there
is no mosaicism for the alteration specified in (15), and that the alteration is present in the gametic cell line
a The defect is sporadic and will not recur
b About half of the male children only will inherit the same alteration
c About half of the children, regardless of sex, will inherit the alteration
d All of the children will inherit the alteration
Problems Section 3
1 A patient with a rare inherited syndrome was found to have 10% of normal enzyme “X” activity Isolation and characterization of the erythrocyte form of the enzyme indicated that the mutant protein differed from itsnormal counterpart by a single amino acid substitution The syndrome
a is due to a regulatory gene mutation
b is caused by the presence of an inhibitor
c is the result of an exonic base substitution
d resulted from a failure in hormonal induction of gene activity
2 Based upon your knowledge of biochemistry and genetics, which of the following observations would indicate that a hormone was specifically inducing enzyme “A” activity?
a An increase in enzyme “A” activity
b An increase in mRNA, rRNA, tRNA, and enzyme “A” activity
c An increase in enzyme “A” mRNA and enzyme “A” activity
d Accumulation of the hormone in the nucleus and the changes observed in 2b
Questions 3–10: Match the following with their appropriate functions in the cell
Trang 43 rRNA a Initiates protein synthesis
ribosomes
precursors
6 HnRNA d Contains DNA elements influencing transcription of a gene
11 Outline transcription and translation using the appropriate base abbreviations and three code words Start
with DNA: AGCTCCAAA and use the table of the genetic code in your biochemistry textbook.
12 HbZ has an altered -chain The amino acid sequence is normal from residue 1 to residue 46 and from residue 70 to the end of the chain Residues 47–69 do not match sequences from any known normal hemoglobin chains How may this mutant hemoglobin arise?
a Substitution of a base in codon 47
b Insertion of a base into codon 46
c Deletion of a base from codon 47
d Insertion of a base into codon 47 and deletion of a base from codon 69
e Deletion of a base from codon 47 and insertion of a base into codon 69
13 Arylsulfatase A is deficient in patients afflicted with the progressive neurological disease, metachromatic leukodystrophy You have successfully purified this enzyme and have prepared a specific antibody against
it You find that immunotitration of extracts of cells cultured from the patient’s skin demonstrates very low levels of arylsulfatase A protein Mutations involving which of the following DNA sequences would explain the low levels of arylsulfatase A protein in this patient?
a The promoter of the arylsulfatase A transcriptional unit
b An exon of the arylsulfatase A transcriptional unit
c A gene affecting the intracellular distribution of arylsulfatase A
d An exon-intron splice junction of the arylsulfatase A transcriptional unit
14 Which of the following structures appear to be physical manifestations of the inactive X chromosome in interphase nuclei?
Trang 5a Barr body c Y body
15 The genetic code consists of triplets derived from four different bases The “degeneracy” of the code may generally be attributed to variation in
a the first nucleotide of the triplet
b the second nucleotide of the triplet
c the third nucleotide of the triplet
d all three nucleotides
Trang 6A simple human gene is illustrated in the above diagram This gene is transcribed from left to right A
mutation at the position of the arrow (asterisk = ATG) would most likely affect
a efficiency of transcription d stability of the mRNA
b accuracy of transcription e initiation of mRNA translation
c processing of the pre-mRNA
b Chain termination may occur such that an incomplete polypeptide is formed
c No change may result
d A shift in the reading frame may occur
2 Why have most attempts to improve the fitness of organisms through induced mutations failed?
a Mutagens are typically nonselective in their points of action
b Most mutations are harmful
c Inappropriate experimental systems have been used
d Mammals are highly sensitive to these mutagens
Questions 3–7: Match the following mutagens with their nuclear effects
Trang 73 X-rays a Thymine dimers
Question 8: True or False
8 The degree of radiation damage is greater in mitotically or meiotically dividing tissue than in nondividing tissue
9 A mutant -globin chain from a patient with hemolytic anemia contained 157 amino acids rather than the normal 146 The amino acid sequence of the mutant -globin chain was identical to the normal chain through amino acid 135; however, the sequences after that point were markedly different Describe the mutation most likely responsible for this patient’s disease
10 The following patterns are observed for a DNA polymorphism after digestion of genomic DNA with the restriction enzyme Eco RI: in males, a fragment of either 9 or 11 kB; in females a fragment of either 9 or
11 kB or both What is the likely origin of these patterns?
Problems Section 5
1 A woman with facioscapulohumeral muscular dystrophy (FMD), an autosomal dominant trait, is seeking advice on having children Her husband, who is 28 and normal, has an uncle with Huntington’s disease (HD; autosomal dominant) His parents are normal, and both are over 50 Symptoms of Huntington’s disease may appear from 12 to 65 years after birth; however, all HD members of his father’s kindred developed signs during their thirties HD and FMD are fully penetrant What are the genetic risks for this couple’s children?
Trang 83 Demonstration of allelism in humans is difficult Assume that two traits are codominant Which of the following tests would be most helpful in suggesting they are determined by allelic genes?
a Failure of a person with both traits to transmit both to the same child
b Lack of occurrence of both traits in the same person
c Lack of a doubly affected child among offspring of two parents, each of whom has only one of the traits
d Absence of normal children from marriages of doubly affected individuals to normal individuals
e Both a and d above
Question 4: True or False
4 A normal ancestry indicates that a trait is not hereditary—even if two or more affected siblings are present in
a family
5.Sickle cell trait describes individuals who are heterozygous for normal hemoglobin HbA and sickle cell
hemoglobin HbS, ie, they are HbS/HbA Two people have sickle cell trait and marry Predict the possible phenotypes of their children and their frequencies Note: sickle cell anemia occurs in HbS homozygotes
a 1/4 sickle cell trait, 1/2 sickle cell anemia, 1/4 normal
b 1/2 normal, 1/2 sickle cell anemia
c 1/2 sickle cell trait, 1/2 sickle cell anemia
d 1/2 normal, 1/2 sickle cell trait
e 1/4 normal, 1/2 sickle cell trait, 1/4 sickle cell anemia
6 Phenylketonuria is a disease resulting from lack of the enzyme, phenylalanine hydroxylase The clinical symptoms of mental and growth retardation, microcephaly, seizures, and eczema are limited to untreated homozygotes Heterozygotes have intermediate levels of enzyme activity in liver extracts Select the correct statement(s)
a Phenylketonuria is a recessive disease
b Phenylketonuria is a dominant disease
c Phenylketonuria is a polygenic trait
d The effects of the normal allele are dominant to those of the abnormal allele
e Both a and d above
7.The genes encoding the variant chains in HbS and HbC are allelic Homozygosity for either gene results in anemia, with HbC disease being much less severe than sickle cell anemia Heterozygosity for either allele and the allele determining the normal chain in HbA results in a normal phenotype What would you predict for the SC heterozygote?
a No disease
Trang 9b Anemia of intermediate severity with respect to sickle cell anemia and HbC disease
c Mild problems like HbC disease
d Sickle cell trait
e This combination of alleles would be fatal
8.A syndrome characterized by multiple congenital malformations and mental retardation was observed to occur twice in this kindred What type of inheritance?
a Autosomal dominant c Autosomal codominant
9 What type of inheritance is responsible for transmission of trait C in this pedigree:
b Autosomal recessive d Autosomal dominant, 2 loci
10 A man has been working as an X-ray technician at a community hospital He and his wife recently had a baby born with cystic fibrosis, an autosomal recessive disease The man has brought suit against the hospital and radiologist, claiming that his occupational exposure to X-irradiation is responsible for the disease in their child He supports his claim by saying there is no history of cystic fibrosis in his nor his wife’s families As presiding judge in this case, how would you rule and why?
Trang 10c Sickle cell anemia
3 What factors may account for your answer in (2)?
a Large differences in mutation rates between populations
b Selective advantage of the heterozygote
c Genetic drift in small founder populations or inbred groups
d Experimental error in determining gene frequencies
4 Trait A is an autosomal dominant exhibiting 80% penetrance Twenty-four affected children out of one
million born to normal parents were observed over a period of 20 years at major hospitals in a western country What is the apparent mutation rate?
c 2.4 x 10-5
5 Do you feel your estimate in question 4 is biased?
a No The estimate is correct
b Yes, because of the possible lack of penetrance in the parents, some of the abnormal alleles were not mutations The estimate may be too high
c Yes, because of the selection of major hospitals only, a bias toward an overestimate or underestimate may be present
d Yes, because of the lack of penetrance in the children, some of the mutations may have been missed The estimate may be too low
6 A population has the following ABO blood group distribution: A = 4,900, B = 1,000, O = 4,000, AB = 100
Calculate the frequencies of ABO A (= p), ABO B (=q), and ABO O (=r).
Trang 11Question 8: True or False
8 Selection against the heterozygote will favor the more common allele
9 Heterozygous advantage is believed to maintain stable polymorphisms in which the frequency of the rarer allele exceeds 1% Which of the following diseases may be maintained by stable polymorphisms?
a Cystic fibrosis (aut rec., 1/2,500)
b PKU (aut rec., 1/15,000)
c Huntington's disease (aut dom., 1/20,000)
d G6PD-deficiency (X-linked rec., 1/10 males of Asian, African, or Mediterranean ancestry)
10 Neighboring Indian tribes in Utah have quite different ABO frequencies Tribe 1 is 100% Type O, and Tribe
2 is 95% Type A Cultural barriers prevent marriage between the tribes, even though they are only a few miles apart What factor is most likely responsible for the difference in allele frequencies?
11 Given that Duchenne muscular dystrophy is an X-linked recessive illness, that the hemizygous males are unable to reproduce, and that 1/3 of all X chromosomes are in males, calculate the frequency of this trait in males if the mutation rate is 1/25,000 Assume this population is at equilibrium
Trang 1214 How is this value interpreted?
a It represents the proportion of heterozygous loci in a common ancestor (with respect to parents of child) rendered homozygous in a child by descent
b It is the chance that an inbred child will inherit a deleterious dominant gene from an ancestor
c It is the chance that an inbred child will develop a recessive disease caused by an allele present in an ancestor
d This is the chance that a given locus heterozygous in a common ancestor will be rendered homozygous
in a child by descent
15 Genetic differences among races generally reflect
a presence or absence of alleles in one race, but not another
b differences in relative frequencies of alleles among the races being compared
c the effects of migration, isolation, and divergent evolution
d the effects of diverse environments upon allele frequencies
Problems Section 7
1 True or False: Maternal serum alpha fetoprotein levels are diagnostic for neural tube defect
2.A woman and her husband are carriers for the autosomal recessive disorder Tay-Sachs disease, thus, both have mutant HEX A genes and have requested first polar body diagnosis PCR and DNA analysis have revealed
the presence of a normal HEXA allele in the polar body How would this result be interpreted?
a The oocyte also has the normal allele
b The Tay-Sachs allele is in the oocyte
c The oocyte contains both the normal and Tay-Sachs alleles
d HEXA alleles are absent from the oocyte.
Questions 3-9 Match the following screening methods with the disease they are designed to detect
3 Method of obtaining fetal blood for karyotyping a RH immune globulin
b 10th week of pregnancy
Trang 134 Usual time at which amniocentesis is performed c cordoentesis
d mosaicisim
5 Increased level when fetus has a neural tube defect e 16th week of pregnancy
f alpha feto protein in materal serum
6 Contains fetal cells viable in culture g aneuploidy
8 Usual time at which CVS is performed i Chrorionic villus
9 Derived from extraembryonic tissue j amniotic fluid
10 A maternal serum screen performed on a pregnant woman shows reduced MSAFP, reduced unconjugated estriol and increased human chorionic gonadotrophin, you do which of the following:
a suspect a neural tube defect and order an ultrasound
b suspect down syndrome and order ultrasound to confirm age of the fetus, note the maternal age and suggest amniocentesis
c diagnose the fetus as having Edward’s syndrome
d order additional screens like pregnancy associated plasma protein
Trang 143 Young mothers with two Down’s syndrome children are victims of fate and need not worry about having a third Down’s syndrome child until after age 40.
4 A man is a balanced carrier for a 13/14 Robertsonian translocation Diagram the division figure that would be observed at Metaphase I of meiotic division.
5 List the chromosome combinations of gametes derived from adjacent and alternate segregation in his cells
6 True or False: This man has a slightly elevated risk for having a child affected with Patau syndrome.Questions 7-11: Match the following karyotypes with their appropriate syndromes
b Balanced translocation carrier
2 Why did you select your answer to question 1?
a Excessive genetic material is not as deleterious if present in even increments
b Chromosomes involved in autosomal trisomies are usually smaller than those participating in sex chromosomal trisomies
c X-inactivation tends to diminish the effects of extra X chromosomes
d The Y chromosome carries few active genes
e Deficiencies of chromosome material are less severe than excesses
3 Which of the following chromosomal aberrations is/are more frequent in abortice series than in liveborn
populations?
Trang 15Questions 6 : True or False
4 Maleness is determined by the ratio of Y to X chromosomes (Y/X > 1)
5 A 27-year-old woman in your care has rarely menstruated, has short stature, neck webbing, and pre-pubertal breast development She appears to have normal intelligence She has been married for six years, but she and her husband have been unable to have children What is your provisional diagnosis?
c Down’s syndrome
6.Why are 46,XY* females infertile (Y* refers to a Y chromosome lacking SRY)?
7.Frequent recombination of genes in the pseudoautosomal regions of the X and Y chromosomes is believed to
occur during male meiosis Rarely this recombination may include SRY, transferring the region to the X
chromosome Predict the appearance of an individual inheriting such a recombinant X chromosome
8 A gene, SHOX, encodes a DNA-binding protein that activates genes contributing to height The gene is
located within the pseudoautosomal region of both the X and Y chromosomes SHOX is not X-inactivated
Why may Turner (45,X) women have short stature?
Problems Section 10
1.Activation of genes appears to be associated with
a modification of chromosome structure
b interaction of steroid hormone-receptor complexes with promoters
c interaction of temporally- and spatially-specific transacting proteins with promoter elements
d interaction of peptide hormones with cyclic AMP-generating systems
2.True or False for 2 and 3:
RNA polymerase only needs to find its promoter sequence in order to initiate transcription
3.The Hox genes are human-specific regulatory genes that encode DNA binding proteins
For 4 –10, match the disorder with the gene that is mutated:
4.Rubenstein-Taybi syndrome-mental retardation a HoxD13
Trang 16Broad thumbs and toes, hirsuit, specific facies b HoxA
12 Waardenburg syndrome is an autosomal dominant condition that accounts for 1.4% of the cases
of congenital deafness In addition to deafness, patients with this condition have atypical facies,
including lateral displacement of the inner canthi and partial albinism A mother has Waardenburg
syndrome, her husband is unaffected, and they plan to have 3 children What is the probability that one of the three children will be affected?
1.Which of the following are reasons to map genes?
a The map position might suggest candidate genes that map to the same position
b Although the identity of the gene causing disease is not precisely known, knowing the map position might allow carrier detection or prenatal diagnosis by linked markers
c comparison of the human and mouse map in their corresponding regions might point to possible animal models for the disease
2.Alternate forms of enzymes X and Y are respectively inherited as autosomal codominant traits Several familieshave been studied to determine whether these loci are linked The cumulative Z scores were (Q=
recombination frequency):
Trang 170 0.00 0.3 +4.25
What would you conclude?
a The loci are unlinked c The loci are 30cM apart
b The loci are 10cM apart d X and Y appear to be determined by allelic genes
3 Consider the following pedigree:
What would you conclude regarding traits A and B?
a The traits are most likely linked
b The traits are assorting independently
c The traits are allelic
d The traits are codominant
4 Assuming the traits are linked, what is the most likely configuration in I–1?
a The genes encoding traits A and B are cis.
b The genes encoding traits A and B are trans.
5 Assuming the traits are linked, which individuals are recombinants?
a II-1, II-2, II-4, III-1, III-4
b II-3, III-2
c II-1, II-4, III-3
d II-2, III-3, III-4
e There are insufficient data to determine recombinants
Trang 186.The F8 gene encodes a clotting factor and is closely linked to G6PD, a second enzyme-encoding locus, on the X
chromosome The daughter of a hemophiliac male (factor 8 deficiency) has two sons, one of whom has
hemophilia like his grandfather The hemophiliac son is G6PD-A, while his normal brother is G6PD-B The A and B G6PD isozymes are inherited as X-linked codominant traits Select the correct chromosomal arrays of the
F8 and G6PD alleles on the X chromosomes of the woman A (/) separates genes on one chromosome from those
on its homolog F8 + = normal allele; F8 o = hemophilia allele.
a is excluded from risk for HD
b is not excluded from risk for HD
c inherited an HD allele from his mother
d The boy’s risk cannot be determined from the information given
Problems Section 12
1 Which of the hemoglobin designations below best describes the relationship of subunits in the
quaternary structure of adult hemoglobin?
2.Blood is drawn from a child with severe anemia and the hemoglobin protein is degraded for
peptide and amino acid analysis Of the results below, which change in hemoglobin primary
structure is most likely to correlate with the clinical phenotype of anemia?
Trang 193.An adolescent presents with shortness of breath during exercise and is found to be anemic A
hemoglobin electrophoresis is performed that is depicted in the figure below The adolescent’s
sample is run with controls including normal, sickle trait, and sickle cell anemia and serum The
adolescent is determined to have an unknown hemoglobinopathy Which one of the lanes contains the adolescent’s sample?
d contains -globin chains rather than -globin chains
5.A particular -globin allele occurs in northern European populations with an average frequency approximating 1/10,000 This allele is most likely maintained in these populations by
Trang 206.Choose from the following: What is the most common mechanism of mutation giving rise to alpha
Thalassemias?
a unequal cross-over between homologous pairs
b equal cross-overs between homologous pairs
c point mutations
d insertional mutagenesis
7 In reference to #6, how would you have answered if the question was “What is the most common
mechanism of mutation giving rise to beta Thalassemias?
8.The locus control region is located 20 kb upstream of the beta genes and their promoters It is responsible for both high level expression as well as the developmental timing of expression of the beta genes How might you imagine this functions?
a the LCR provides an open chromatin domain that gives transcription factors access to the regulatory elements in the cluster
b It acts a super-enhancer for transcription
c It is highly homologous to the introns of the immunoglobulin locus facilitating class switching
d It packs tighly around histones
9.A woman has sickle cell trait and her mate is heterozygous for Hb C What is the probability that there child will have no normal hemoglobin?
Match the following for 10-19:
12 # of alpha globin genes missing in HbH 3 beta-Thalassemia
13 2 different mutant alleles at a locus 4 alpha-Thalassemia
14 prenatal diagnosis of sickle cell disease 5 high-level beta chain expression
16 # of alpha globin genes missing in 7 genetic compound
hydrops fetalis with Hb Bart
Problems Section 13
Trang 21Data for Questions 1–4: A young girl presented with mental deterioration, failure to thrive, poor motor
development, hepatosplenomegaly, and generalized aminoaciduria The patient died two months after
hospitalization The autopsy report mentioned dense-staining cellular inclusions in neuronal elements of the cerebral cortex, basal ganglia, and cerebellum Metachromatic granules were also observed in liver, spleen, and kidney Liver biopsy specimens obtained prior to the patient’s death lacked superzymase activity, and very low levels of this enzyme were found in fresh brain, kidney, and spleen preparations taken at autopsy Superzymase isalso expressed in leukocytes Both the father and mother of this patient possessed leukocyte superzymase
activities that were about half normal Both parents have normal clinical phenotypes An older brother of the patient died several years earlier from a disease that resembled that in the patient The remainder of the family history is negative for the disease
1 What type of inheritance best explains the transmission of the disease in this family?
a Autosomal dominant d X-linked recessive
c X-linked dominant
2.How would you explain the patient’s clinical symptoms?
a The symptoms are most likely caused by two genes: one responsible for the mental effects, and one causing the physical problems
b The symptoms are the result of several genes, each causing one feature of the disease
c One gene encodes superzymase, and all of the effects are caused by a central block created by
deficiency of this enzyme
d Two recessive mutations are involved: one causing superzymase deficiency, and the other responsible for loss of a transport substance that is a common carrier for all of the amino acids appearing in the urine
e None of the above
3 How would you account for the tissue differences in superzymase activity?
a Modifiers in each tissue affect the expression of the superzymase structural gene
b Inhibitors in the liver totally block superzymase expression in that tissue
c More than one isozyme of superzymase exists Liver has only one isozyme, while other tissues possess more superzymase isozymes The mutation only affects the isozyme expressed in both liver and other tissues
d More than one isozyme of superzymase exists Liver contains at least two isozymes, while other tissues have one The mutation affects the enzyme shared by all tissues
4 How would you explain the granules present in the cells of this patient?
a They may be accumulations of the substrate of superzymase
Trang 22b They could be aggregations of a byproduct produced by a salvage pathway that usually does not operate at significant levels in normal cells.
c The granules may contain the substrate of another enzyme that is inhibited by high quantities of the substrate of superzymase
d They are viral particles that were coincidentally observed in these tissues
5 Which of the following traits illustrates the concept of genetic predisposition for human disease?
c AAT deficiency
6 A couple has a child who has been diagnosed with a medium chain acyl coenzyme A dehydrogenase deficiency (MCAD), a condition that affects the body’s ability to metabolize medium chain fatty acids This couple is now expecting another child Given what you know about the inheritance of metabolic disorders, what is the risk that this child will have MCAD?
7 How may the blood and urine levels of a patient with a mutation affecting the intracellular metabolism of an amino acid differ from those of a patient who has abnormal transport of that amino acid across his proximal tubule membranes?
8 Consider the following pathway:
Predict the consequences of a block between C and D
9 Tay-Sachs disease causes cherry red spots in the eye, ‘startle’responses in infancy, neurodegeneration and death Heterozygotes with an abnormal Tay-Sachs allele are termed carriers What is the risk that the
grandmother of an affected child is a carrier?
Questions 10–13 Match the following diseases with their enzyme/protein deficiency
12 Familial Type IIa Hypercholesterolemia c Hexosaminidase B
e Hexosaminidase A
Trang 23f LDL-receptor
14 A girl seems normal at birth but begins flinching at loud noises (enhanced startle response) at age 6 months Opthalmologic examination reveals a central red area of the retina surrounded by white tissue (cherry red spot) The child initially can sit up, but then regresses so that she can’t roll over or recognize her parents Her physician suspects a lipid storage disease (neurolipidosis) If the diagnosis is correct, what is the risk that the next child of these parents will be affected with the same disease?
The cause of Tay-Sachs disease is best described by which of the following?
a excess of lysosomal enzyme in blood due to defective uptake
b deficiency of a lysosomal enzyme that digests proteoglycans
c deficiency of a membrane receptor that takes up proteoglycans
d deficiency of a mitochondrial enzyme that degrades glycogen
15 A woman who married her first cousin wants to know what the risk of having a child with cystic fibrosis
is because her grandmother, who is also her husband’s grandmother, died of cystic fibrosis
16 Which of the following is most likely in an untreated child with PKU?
a elevated tyrosine
b increased skin pigmentation
c decreased skin pigmentation
d normal phenylalanine hydroxylase levels
e elevated alanine
Problems Section 14
1 A mutation in the pro alpha 1 chain of collagen is in general more deleterious than
a mutation in the pro alpha 2 gene of collagen for which of the following reasons:
a post-translational modifications only occur on pro alpha chain1
b post-translational modifications only occur on pro alpha chain 2
c collagen molecules are formed by 2 pro alpha 1 chains and 1 pro alpha 2 chain
d pro alpha 1 is the only chain able to associate with elastin
2 Mutations in pro alpha 1 chain lead to what kind of ratio of normal to mutant collagen chains?
3 Which of the characteristics below apply to the amino acid glycine?
a has a hydrogen for a side chain, thus, is small
b large molecular diameter interfering with alpha helix formation
c hydrophilic, basic and charged
d hydrophobic
Trang 244 Amino acid hydroxylation requires the reducing agent ascorbic acid, which is also known as vitamin C Scurvy, results from a deficiency of vitamin C Which of the following symptoms might you expect to see in individuals with scurvy?
a neural tube defects.
b Mental retardation
c Brittle bones with fractures and bleeding tendencies
d Digestion problems
5 Why did you answer 4 the way you did?
6 Little People of America is a support group for individuals with short stature that conducts many workshops and social activities Two individuals with achondroplasia meet and decide to marry and have children What is their risk of having a child with dwarfism?
7 The diagnosis of osteogenesis imperfecta is most accurately performed by which of the following?
a PCR amplification and DNA sequencing of type I collagen gene segments to look for point
mutations
b Gel electrophoresis of labeled type I collagen chains synthesized in fibroblasts
c PCR amplification and ASO hybridization to detect particular alleles
d Northern blot analysis to examine RNA levels and size
e Purfication and trypsin digestion of type 1 collagen to examine the peptides by 2 D gel
electrophoresis
8 A patient with Marfan’s syndrome is evaluated at a clinic He is noted to have a tall, thin body, loose joints
and arachnodactyly Opthalmologic examinination reveals lens dislocation Echocardiogram reveals dilation of the aortic root A family history reveals that the patient’s parents are normal but that this paternal grandfather and great-grandfather died in their 40s with lens dislocation and dissecting aortic aneurysms A sister is found to have a similar body habitus, dilation of the aortic root and normal lenses The different findings in these family members with the same disease is best described as:
Trang 259 Marfan’s syndrome is caused by which of the following mechanisms?
a mutation that prevents addition of carbohydrate residues to the fibrillin glycoprotein
b mutation in a carbohydrate portion of fibrillin
c mutation that disrupts a secondary structure of fibrillin and blocks its assembly into microfibrils
d mutation in a lysosomal enzyme that degrades fibrillin
e mutation in a membrane receptor that targets fibrillin to lysosomes
Problems Section 15
1.Bill is the only person in his family affected with Duchenne muscular dystrophy He has one unaffected brother Joe DNA analysis shows that Bill has a deletion in the DMD gene Joe received the same maternal X chromosome but without the deletion What happened to account for this?
a Bill and Joe have different fathers
b Bill arose from a new mutation on the X chromosome from his mother
c The mother may be a mosaic and the mosaicism occurred in her germline
d The father is a mosaic and the mosaicism occurred in his germline
2 A woman with a hemophiliac father is married to a man with Becker muscular dystrophy Both traits are inherited as X-linked recessives Patients with this mild form of muscular dystrophy are fertile and are usually not confined to a wheelchair until their forties What types of children may they have?
a 1/2 at risk for dystrophy; 1/2 normal 1/2 hemophiliac; 1/2 normal
d 1/2 hemophiliac; 1/2 at risk for dystrophy 1/2 hemophiliac; 1/2 normal
e 1/2 at risk for dystrophy; 1/2 hemophiliac 1/2 hemophiliac; 1/2 normal
Question 3: True or False
3 A phenotypically normal woman and a protanopic (red-blind) man cannot have a colorblind son
4 Anhydrotic ectodermal dysplasia (AED) is inherited as an X-linked recessive trait A daughter of a normal man and heterozygous woman has AED What is the most probable cause for the appearance of AED in thisgirl?
a Deletion of her normal allele d Homozygosity for the trait allele
b X-inactivation of her normal allele e Both b and c above
Trang 265 What type of inheritance is most likely responsible for inheritance of the trait in the above pedigree?
a X-linked dominant d Autosomal dominant
b X-linked recessive e Y-linkage
b She would be normal
c She would be affected
d Her phenotype would usually be normal, but occasional affected heterozygotes would be anticipated when X-inactivation in different cells silenced most of their normal G6PD alleles
e None of the above
7 Duchenne muscular dystrophy has a high mutation rate but shows no ethnic variation in frequency Using your knowledge of the dystrophin gene and the genetics of this disorder, choose the best explanation for whythis disorder is equally frequent in all populations:
a Intrachromosomal recombination occurs on the X chromosome to give rise to this deletion
b The large size of the dystrophin gene makes it an easy target for mutation
c There is heterozygote advantage to having a mutation in the dystrophin gene
d Point mutations in tbe promoter can occur in all races
8 XGA is an X-linked trait with lack of Xg(a) antigen being recessive to its presence G6PD is also X-linked,
and the presence of enzyme activity is dominant to its absence Phenotypes of individual erythrocytes can
be scored by using a fluorescent antibody specific for Xg(a) and a stain for G6PD activity If a woman is
heterozygous at both loci and G6PD but not XGA is subject to X-inactivation, what pattern of erythrocytes
would you expect to see after treating them with the two reagents?
9 Amelogenesis imperfecta (hereditary enamel hypoplasia) is inherited as an X-linked dominant trait Males have a very thin, smooth layer of enamel which appears homogeneous Heterozygous females have
irregularly thick and thin enamel, often having the appearance of vertical grooves How would you explain this sex difference?
a Random X-inactivation leads to sectors of mutant and normal cells
b Somatic mutation limited to the female
c The trait is really dominant in males and recessive in females
d The groove pattern is environmentally determined
Trang 27Data for Questions 10–14: The Bruton form of hypogammaglobulinemia is inherited as an X-linked recessive Circulating antibodies in these patients are grossly deficient A woman had two brothers die from the disease Both of her parents and her husband have normal levels of gamma-globulin and normal antibody function.
10 What is the probability that this woman is a heterozygote?
13 Why did you select the above response?
a Risks based upon single-factor inheritance never change
b The genotype of the mother is established
c The genotype of the mother is unknown
d Risk to a future child decreases with increasing numbers of normal events, as long as the mother's genotype has not been established
e Both c and d above
14 Suppose this woman produced a normal daughter and two normal sons What is the probability that the woman is a carrier?
Trang 2816 In most patients with gout as well as those with Lesch-nyhan syndrome, purines are overproduced and overexcreted Yet the hypoxanthine analog allopurinol, which effectively treats gout, has no effect on the severe neurological symptoms of Lesch-Nyhan patients because it does not
a decrease de novo purine synthesis
b decrease de novo pyrimidine synthesis
c diminish urate synthesis
d increase phosphoribosylpyrophosphate levels
17 The most common intrachromosomal recombination event resulting in an inversion is the cause of which of the following diseases:
a Duchenne muscular dystrophy
b Becker muscular dystrophy
c Glucose 6 phosphate dehydrogenase deficiency
d Hemophilia A
e Hemophilia B
Problems Section 16
For 1-13, match the disorder with the description
1 RNA binding protein a Friedreich’s ataxia
4 mitochondrial protein d Huntington’s disease
5 hyper-methylation inhibits RNApolymerase from transcribing the gene
6 coding-region polyglutamine expansion
7 anticipation
8 abnormally high levels of iron in their heart tissue
9 free radical damage
10 expansion occurs during male meiosis
11 expansion occurs during female meiosis
12 may be caused by depletion of an RNA binding protein
13 autosomal recessive
14 A woman presents to you because she is concerned about her unborn child She tells you that she has a brother who looks normal but is “ a little slow” and whose speech is difficult to understand Although