Deck 6: Genetics

Question 1

A 15-year-old girl is brought to the physician for evaluation of primary amenorrhea.  Her mother is concerned because her other daughters had menarche before age 13.  Vital signs are normal.  The patient is at the 5th percentile for height and 20th percentile for weight.  Examination shows a high arched palate and Tanner stage I breasts with inverted and widely spaced nipples.  Further evaluation would most likely show which of the following?

A)Absent uterus
B)Ambiguous genitalia
C)Atrophic ovaries
D)Fibrosed fallopian tubes
E)Hirsutism
F)Vaginal agenesis

Answer 1

C

Primary amenorrhea is defined as the absence of menses by age 15 in someone who has normal growth and secondary sexual characteristics (eg, body hair growth, breast development) or absence of menses by age 13 in girls without secondary sex characteristics.  Chromosomal abnormalities resulting in ovarian insufficiency are the most common cause of primary amenorrhea.
This patient's short stature, high arched palate, Tanner I breasts, and widely spaced nipples are characteristic of Turner syndrome (45,XO).  Patients with Turner syndrome have a variable degree of ovarian dysgenesis.  The ovaries usually appear underdeveloped and atrophic ("streak gonads") due to in utero degeneration of the ovarian follicles with replacement by fibrotic tissue.  Since menstruation and breast development are estrogen-dependent processes, they do not occur because the ovaries are nonfunctional.
(Choice A)  Although patients with Turner syndrome may have streak ovaries, the uterus should be present.  An absent uterus and primary amenorrhea can be seen in Müllerian agenesis and androgen insensitivity syndrome.
(Choice B)  Turner syndrome patients have normal female external genitalia.  Ambiguous external genitalia can be seen in 46,XX patients with congenital adrenal hyperplasia.
(Choice D)  Fibrotic fallopian tubes are not seen in Turner syndrome but are sometimes seen in pelvic inflammatory disease.
(Choice E)  Hirsutism and secondary amenorrhea can be seen in polycystic ovarian syndrome.
(Choice F)  Vaginal agenesis results from absence or underdevelopment of the Müllerian ductal system (Müllerian agenesis).  Although patients with Müllerian agenesis have primary amenorrhea, they will have normal palate and breast development.
Educational objective:
Common manifestations of Turner syndrome include primary amenorrhea, short stature, a high arched palate, and widely spaced nipples.  Primary amenorrhea occurs in these patients due to in utero degeneration of the ovarian follicles (gonadal dysgenesis).
__________
References:
The patient with Turner syndrome: puberty and medical management concerns.
(http://www.ncbi.nlm.nih.gov/pubmed/22884020)

Question 2

A cell biologist is studying the role of ribonucleoproteins in normal cellular function.  He prepares a cell extract using a specific cell type obtained from a 73-year-old man.  Ribonucleoproteins are separated and purified from the cell extract for structural and functional analyses.  These cells are found to express higher amounts of a particular protein in comparison to other cell types.  This protein has reverse transcriptase activity that functions to add TTAGGG repeats to the 3' end of chromosomes.  Which of the following cell types was most likely studied in this experiment?

A)Epidermal basal cells
B)Erythrocytes
C)Myocardial cells
D)Neurons
E)Pancreatic β cells

Answer 2

A

Telomerase is a ribonucleoprotein that adds TTAGGG repeats to the 3' end of chromosomes (telomere region).  It is similar to other reverse transcriptase enzymes in that it synthesizes single-stranded DNA using single-stranded RNA as a template (RNA-dependent DNA polymerase).  Telomerase is composed of 2 main subunits, the telomerase reverse transcriptase (TERT) subunit and the telomerase RNA component (TERC).  TERC is a "built-in" RNA template that is repeatedly read by the TERT subunit to add TTAGGG DNA sequence repeats to telomeres.
Stem cells have very long telomeres due to their high telomerase activity, allowing them to proliferate indefinitely in a controlled manner.  In contrast, most terminally differentiated adult somatic cells (eg, myocardial cells, neurons, pancreatic β cells) have short telomeres as they do not express telomerase and their telomeres shorten with every cell division (Choices C, D, and E).  Critical shortening in telomere length is thought to be a signal for programmed cell death.  In fact, syndromes of premature aging (eg, Bloom syndrome) are associated with shortened telomeres.  In contrast, cancer cells upregulate their telomerase activity, preventing cell death by maintaining their telomere length.
Stem cells are undifferentiated cells with the potential to differentiate into other cell types and can be classified as either embryonic or adult stem cells.  Although embryonic stem cells are present in the very early stages of embryogenesis and can give rise to every cell type in adult humans (pluripotent), adult stem cells are present in most tissues and are generally responsible for replacing dead cells.  For example, the epidermis is continuously replaced by stem cells present in the basal cell layers.  Bone marrow stem cells similarly replace peripheral red and white blood cells.
(Choice B)  Erythrocytes have no nuclei and therefore have no potential to divide.
Educational objective:
Critical shortening in telomere length can signal for programmed cell death.  Telomerase is a reverse transcriptase (RNA-dependent DNA polymerase) that lengthens telomeres by adding TTAGGG repeats to the 3' end of chromosomes.  Stem cells have long telomeres due to high telomerase activity, allowing them to proliferate indefinitely in a controlled manner.
__________
References:
Telomere structure and telomerase in health and disease (review).
(http://www.ncbi.nlm.nih.gov/pubmed/22941386)

Question 3

A 22-year-old woman presents to clinic for a medical check-up.  She has been diagnosed with Turner's syndrome.  Cardiovascular examination reveals no abnormalities of the heart or aorta.  She asks about her chances of having a baby.  Which of the following methods could be used to achieve pregnancy in this patient?

A)Bromocriptine therapy
B)Clomiphene citrate
C)Pulsatile GnRH infusion
D)hCG therapy
E)In vitro fertilization (IVF)

Answer 3

E
Most women with Turner syndrome (45,XO) are infertile secondary to ovarian failure.  With sufficient estrogen and progestin supplementation, however, these women can develop a thick endometrial lining that is substantial enough to support a pregnancy.  In vitro fertilization of Turner syndrome patients with an ovum provided by a related or anonymous donor results in pregnancy rates approaching 60%.  A thorough renal, cardiac and thyroid examination should be carried out before pregnancy is attempted to reduce the potential for complications during pregnancy.  Pregnancy can occur spontaneously in some patients with Turner syndrome, but the risk of spontaneous abortion, Down syndrome and Turner syndrome are all increased in such cases.
(Choice A) Bromocriptine is a dopamine receptor agonist that inhibits pituitary prolactin secretion.  It can restore fertility in women with hyperprolactinemia.
(Choice B) Clomiphene citrate is an antiestrogen that stimulates ovulation by blocking the feedback inhibition of estrogen on the hypothalamus thereby enhancing the release of pituitary gonadotropins.  It is best used to achieve fertility in women with ovulatory failure who are normogonadotropic, normoprolactinemic and euthyroid.
(Choice C) Pulsatile GnRH infusion can stimulate ovulation in women who have disordered hypothalamic GnRH secretion resulting in hypogonadotropic, hypogonadal anovulation.  Pituitary and ovarian function must be intact for this method to work.
(Choice D) hCG therapy can be used to trigger the ovulatory cascade in an oocyte donor when her follicles are deemed mature.
Educational objective:
In vitro fertilization using a donated ovum is the most promising means of achieving pregnancy in a woman with Turner syndrome.  Pregnancy can occasionally occur spontaneously in some patients with Turner syndrome, but the risk of spontaneous abortion, Down syndrome and Turner syndrome are all increased in such cases.

Question 4

A married couple comes to the physician for routine prenatal counseling.  The husband is 120 cm (3 ft 11 in) tall with disproportionately short upper and lower extremities, a large head, and a prominent forehead.  He is unable to provide a biological family history as he was adopted.  His spouse is of average height with normal constitutional features, and her family history is insignificant.  They are concerned about their unborn child's height.  Which of the following is the best response to their concerns?

A)The condition is not inheritable
B)The risk depends on the child's biological sex
C)The risk depends on the mother's carrier status
D)The risk for the child to be short is about 25%
E)The risk for the child to be short is about 50%

Question 5

A 12-year-old girl is brought to the physician by her parents, who are concerned about her loss of interest in playing sports at school.  During a recent competition, she walked off the field in the middle of the game, complaining about the pain in her legs.  The patient has no other medical conditions and takes no medications.  Her vaccination schedule is up-to-date.  Physical examination shows pulsatile vessels within the intercostal spaces and diminished femoral pulses relative to brachial pulses.  This patient's symptoms are most likely associated with which of the following conditions?

A)DiGeorge syndrome
B)Down syndrome
C)Friedreich ataxia
D)Kartagener syndrome
E)Marfan syndrome
F)Tuberous sclerosis
G)Turner syndrome

Question 6

A 10-year-old girl is brought to the office for evaluation of short stature.  She was an average-sized infant, but over the past few years, her height growth velocity has plateaued.  The patient has not menstruated and has no symptoms.  She takes no medications, has no allergies, and has received all recommended immunizations.  Menarche occurred in her mother at age 14 and both of her parents are tall.  The patient's height is at the <5th percentile and weight is at the 50th percentile for age and sex.  She has no breast buds and no axillary or pubic hair.  She has a low hairline, a short and wide neck, a broad chest, and widely spaced nipples.  Which of the following is the most likely underlying mechanism for this patient's condition?

A)Balanced translocation
B)Frameshift mutation
C)Meiotic nondisjunction
D)Trinucleotide repeat expansion
E)Uniparental disomy

Question 7

A 14-year-old girl is brought to the office for a routine physical examination.  The patient will be starting her freshman year of high school soon.  She plays the clarinet in the school band but does not play any sports.  The patient says that she is not sexually active and does not use tobacco, alcohol, or illicit drugs.  Height is at the 5th percentile, and weight is at the 25th percentile.  Her temperature is 36.7 C (98 F), blood pressure is 120/80 mm Hg, pulse is 88/min, and respirations are 16/min.  Physical examination shows a short and thick neck, a broad chest, and shortened fourth metacarpals bilaterally.  A murmur is heard on cardiac auscultation.  Which of the following would most likely be seen in an echocardiogram?

A)Atrial septal defect
B)Bicuspid aortic valve
C)Mitral stenosis
D)Mitral valve prolapse
E)Patent ductus arteriosus
F)Ventricular septal defect

Question 8

A 67-year-old man comes to the office due to dark urine, pale-appearing stools, and progressive yellowing of his eyes over the last few weeks.  He also reports unintentional weight loss, but has had no night sweats, abdominal pain, bloody stools, or vomiting.  He has no chronic medical conditions and takes no medication.  Vital signs are within normal limits.  Scleral icterus is present.  The neck is supple.  No lymphadenopathy or skin abnormalities are present.  There is no hepatosplenomegaly.  Laboratory results are as follows: CT scan of the abdomen reveals a pancreatic mass compressing the common bile duct and the pancreatic duct.  This patient's disease process is most likely caused by a mutation affecting which of the following genes?

A)APC
B)BCL2
C)BRAF
D)c-MYC
E)KRAS

Question 9

A 2-month-old boy is brought to the emergency department due to progressively worsening "floppiness" and poor feeding.  The infant was born in Eastern Europe via an uncomplicated vaginal delivery to a 38-year-old woman and then immigrated to the United States with his family.  The parents describe the infant as a "good baby" who rarely cries and sleeps through the night but has lately been difficult to rouse for breastfeeding.  Stools have also decreased to every other day and are small and pellet-like.  Physical examination shows a hypotonic infant with a large anterior fontanelle, large tongue, and a reducible umbilical hernia.  He has low tone and is unable to hold his head erect on his own.  No other abnormalities are seen.  Which of the following is the most likely cause of this patient's condition?

A)Botulism
B)Down syndrome
C)Galactosemia
D)Hirschsprung disease
E)Hypothyroidism
F)Phenylketonuria

Question 10

A newborn girl is evaluated in the nursery after an uncomplicated spontaneous vaginal delivery to a 29-year-old primigravida.  The mother declined prenatal testing and ultrasound examination during the pregnancy.  Her pregnancy was otherwise uneventful, and she took prenatal vitamins throughout.  Examination of the neonate shows a posterior neck mass and bilateral nonpitting edema of the hands and feet.  Femoral pulses are diminished.  Neck ultrasound reveals a mass composed of cystic spaces separated by connective tissue.  Which of the following is the most likely underlying mechanism responsible for this patient's condition?

A)21-hydroxylase deficiency
B)Androgen receptor mutation
C)Loss of paternal chromosome X
D)Meiotic nondisjunction of fetal chromosome 18
E)Partial deletion of the short arm of chromosome 5
F)Robertsonian translocation involving fetal chromosome 21

Question 11

An 18-year-old woman comes to the office for evaluation of graying hair.  The patient has no other concerns and has otherwise been healthy.  She reports that her mother had similar features at a young age and died of progressive pulmonary fibrosis.  Examination shows diffuse gray hair.  There are white patches on the surface of the tongue.  Cardiopulmonary examination is unremarkable, and the abdomen is soft and nondistended.  Skin examination shows areas of reticular hyperpigmentation on the neck and torso.  The nails of the fingers and toes appear thin.  Genetic testing reveals a loss-of-function mutation affecting the telomerase reverse transcriptase gene.  Which of the following cell types is most likely to be affected by this mutation?

A)Cardiac myocytes
B)CNS neurons
C)Compact bone osteocytes
D)Hematopoietic stem cells
E)Secondary oocytes
F)Vascular endothelial cells

Question 12

A 40-year-old woman, gravida 5, para 0, aborta 4, at 12 weeks gestation comes to the emergency department due to vaginal bleeding, midline pelvic pain, and severe nausea and vomiting.  She has a history of 4 prior first trimester losses.  Pelvic examination shows a 16-week-sized uterus.  Speculum examination reveals dark red blood in the vagina.  A β-hCG level is >100,000 mIU/mL, and an ultrasound shows no fetus and a uterine cavity filled with multiple small cysts.  The patient undergoes dilation and curettage in the operating room, and a friable mass of tissue consisting of many thin-walled cysts is evacuated from her uterus.  Examination of the tissue would most likely show which of the following karyotypes?

A)46,XX
B)46,XY
C)47,XXX
D)47,XXY
E)69,XXX
F)69,XXY

Question 13

A 32-year-old woman comes to the office due to worry that she will go bald.  Her father had a receding hairline with apical baldness beginning at age 20 and was completely bald by age 35.  The patient's paternal grandmother and multiple other relatives on her paternal side also had early-onset baldness, but her father's siblings and the maternal side of her family have had no problems with unusual hair loss.  Physical examination shows mild thinning of hair at the temporal areas, with an otherwise normal hairline, thickness, and coloration.  There is no excess hair growth on her face or trunk, and she has a normal female pattern of pubic hair growth.  Palpation of the thyroid is normal.  Which of the following is the most likely inheritance pattern of the hair loss in this patient's family?

A)Autosomal dominant
B)Autosomal recessive
C)Mitochondrial
D)Polygenic
E)Sporadic

Question 14

A 20-year-old man suddenly collapses while walking on a college campus.  He is found to be unresponsive and pulseless by a bystander.  Despite efforts by emergency medical personnel, the man is unable to be resuscitated.  His friends say he appeared fatigued and described palpitations and dyspnea with exertion in the weeks leading up to the event.  He had no known medical history and did not use tobacco, alcohol, or illicit drugs.  The man's 3 younger siblings are healthy.  His parents confirm a history of "early heart disease" in a paternal grandfather and request an autopsy and genetic testing for further evaluation.  Genetic studies reveal a defect in a TTN gene exon resulting in a truncated titin protein.  Autopsy findings are most likely to show which of the following phenotypes?

A)Arrhythmogenic right ventricular cardiomyopathy
B)Bicuspid aortic valve
C)Dilated cardiomyopathy
D)Hypertrophic cardiomyopathy
E)Restrictive cardiomyopathy

Question 15

A mutation in a non-coding DNA sequence is believed to affect expression of the gene coding for a specific fetal enzyme.  Liver and bone marrow cells from the fetus and his parents are obtained.  Which of the following is the best method to determine if this gene is being transcribed in cultures of the isolated cells?

A)Northern blot
B)Western blot
C)Southern blot
D)Southwestern blot
E)Enzyme-linked immunosorbent assay

Question 16

A 22-year-old woman, who recently relocated, comes to the office for a new patient visit.  She has mild intellectual disability and has completed a high school level of education.  The patient has no major health problems but reports persistent swelling of the hands and feet.  Menarche occurred at age 13, and she has regular menstrual cycles.  Physical examination shows short stature and a webbed neck.  Karyotype analysis performed on peripheral leukocytes shows that 40% of the cells have a 45,X genotype and that the remaining 60% contain a 46,XX genotype.  Which of the following is the most likely cause of this patient's condition?

A)Chromosomal deletion
B)Complete monosomy X
C)Germline mosaicism
D)Somatic mosaicism
E)Uniparental disomy
F)X chromosome inactivation

Question 17

A healthy 31-year-old woman comes to the office as she and her husband desire a second child.  The husband is infertile and the patient's son, who was conceived via donor insemination, was recently diagnosed with glycogen storage disease type II (Pompe disease).  This rare autosomal recessive disease is known to affect 1 in 40,000 of the general population.  Genetic testing confirms that the patient is a carrier for the disease.  A different sperm donor is selected with no personal or family history of Pompe disease; however, his carrier status is unknown.  What is the probability of the patient having an affected child with the new sperm donor?

A)1/4
B)1/240
C)1/400
D)1/800
E)1/40,000
F)1/160,000

Question 18

An autopsy was performed on a 17-year-old girl after a fatal motor vehicle collision.  Her ovaries appear small and underdeveloped on gross examination.  Light microscopic examination shows ovaries primarily composed of connective tissue with no follicles.  Which of the additional abnormalities is most likely to be found on postmortem examination?

A)Bicuspid aortic valve
B)Inspissated pancreatic ducts
C)Lens displacement
D)Mitral valve prolapse
E)Vaginal adenosis

Question 19

A 1-day-old infant in the newborn nursery is found to have a harsh, holosystolic murmur on physical examination.  The neonate was born at 39 weeks gestation to a 36-year-old woman who opted to defer prenatal screening.  Review of medical records shows no family history of genetic or chromosomal disorders.  The infant's vital signs are appropriate for his age.  The rest of the physical examination shows a flat facial profile, protruding tongue, and small ears.  Which of the following most likely occurred prior to conception?

A)Chromosomal deletion
B)Chromosomal translocation
C)Gene inactivation
D)Meiotic nondisjunction
E)Trinucleotide repeat expansion

Question 20

A primigravid woman at 22 weeks gestation comes to the office with her partner to discuss a cleft lip and palate identified on prenatal ultrasound.  The father requests a paternity test of the fetus because no one on his side of the family has ever had a cleft lip or palate.  During your discussion with the family, you explain to them that children with cleft lip and palate often have no family history of the condition because it is most commonly due to which of the following?

A)Autosomal recessive inheritance
B)Embryologic disruption
C)Mitochondrial mutations
D)Polygenetic and environmental interactions
E)Skewed X-inactivation

Question 21

A 65-year-old woman with chronic obstructive pulmonary disease and type II diabetes mellitus comes to the emergency department due to profound fevers and malaise.  After initial evaluation, she is hospitalized for septicemia.  Blood cultures plated on lactose-containing media grow rapidly dividing gram-negative bacteria.  Replication of these microbial cells requires synthesis of two daughter strands of DNA using the parent strands as templates.  Which of the following processes will differ the most between the 2 daughter strands formed at each replication fork?

A)Enzymatic function of DNA helicase
B)Interaction with single-stranded DNA-binding proteins
C)Joining of DNA fragments by ligase
D)Proofreading of the newly synthesized DNA
E)Relief of supercoils by topoisomerase

Question 22

A 14-year-old boy experiences severe, prolonged bleeding following a tooth extraction.  He also has a history of multiple episodes of painful joint swelling following minor trauma.  His parents have no bleeding problems.  Evaluation shows that the patient has an inherited disorder and that one of his parents is a genetic carrier.  His older sister, who does not have this condition, is pregnant.  She does not know the sex of her child.  She asks about the risk that her child will be affected.  Which of the following is the best estimate that this child will have the disease?

A)Near 0
B)1/2
C)1/4
D)1/8
E)1/16
F)1/32

Question 23

Electron microscopy of a eukaryotic cell during interphase of the cell cycle shows 10-nm thick chromatin fibers with a "beads on a string" appearance.  These chromatin fibers are extracted and treated with an endonuclease, which preferentially cleaves the "string" portions of the chromatin.  Further evaluation of the "beads" reveals that they are composed of DNA wrapped around a core of proteins.  Which of the following proteins is most likely found outside of this core and helps promote chromatin compaction?

A)Histone H1
B)Histone H3
C)Histone H4
D)snRNP
E)Topoisomerase II
F)Ubiquitin

Question 24

A research scientist purifies DNA polymerase III from Escherichia coli extract.  When the enzyme is incubated in a mixture containing DNA templates, RNA primer oligonucleotides, and tagged deoxynucleotides, she finds that the enzyme possesses 3' to 5' exonuclease activity.  Which of the following enzymatic actions was most likely observed during the experiment?

A)Cleavage of DNA strands to remove supercoils
B)Excision of thymine dimers within DNA
C)Removal of mismatched base pairs during DNA replication
D)Removal of RNA primer nucleotides
E)Unwinding of the 2 strands of template DNA

Question 25

A 35-year-old woman, gravida 1 para 0, at 20 weeks gestation comes to the office for a routine prenatal visit and fetal anatomy ultrasound.  The ultrasound reveals several abnormalities.  An amniocentesis is performed and a fetal karyotype analysis is ordered; the results are shown in the image below: This fetus is at greatest risk for developing which of the following conditions after birth?

A)Acute lymphoblastic leukemia
B)Aplastic anemia
C)Chronic myelogenous leukemia
D)Germ cell tumor
E)Retinoblastoma
F)Rhabdomyosarcoma

Question 26

A 1-hour-old girl born to a 40-year-old woman is brought to the nursery for evaluation.  The pregnancy and delivery were uncomplicated.  Physical examination shows mid-face hypoplasia with a flat nasal bridge, up-slanting palpebral fissures, a small mouth, and a single palmar crease bilaterally.  Cardiac auscultation reveals a blowing holosystolic murmur heard best along the sternal border.  Which of the following abnormalities is most likely to be present in this patient?

A)Aberrant genomic imprinting
B)Mosaicism
C)Partial deletion
D)Triplet expansion
E)Uniparental disomy

Question 27

A 25-year-old man experiences severe intolerance to certain medications.  On 2 occasions, his reactions to various drugs have necessitated hospital admission.  His family pedigree with respect to this condition is shown below, with the red arrow indicating his position within the family. Assuming that the genetic condition demonstrates complete penetrance and is rare in the general population, which of the following inheritance patterns is most likely?

A)Autosomal dominant
B)Autosomal recessive
C)X-linked dominant
D)X-linked recessive
E)Mitochondrial

Question 28

Pharmacologic researchers develop a novel alkylating chemotherapeutic agent against glioblastoma multiforme.  They find that malignant cells with methylation of the promoter region for the O⁶-methylguanine-DNA methyltransferase (MGMT) gene are more susceptible to this drug than cells without methylation.  Which of the following is the most likely function of the protein encoded by the gene?

A)Induction of apoptosis
B)Reducing major histocompatibility complex expression
C)Repairing DNA damage
D)Upregulation of telomerase

Question 29

An infant born to a 34-year-old woman has a flat facial profile, prominent epicanthal folds, and a holosystolic murmur heard loudest at the left sternal border.  Karyotype analysis is consistent with trisomy 21.  Maternal and paternal karyotypes are normal.  A restriction fragment length polymorphism (RFLP) analysis is conducted to determine the parental origin of the extra chromosome.  DNA samples from the child, mother, and father are obtained and the DNA is fragmented with a restriction enzyme.  The fragments are then sorted by size using the Southern blot technique.  Labeling is done using a probe that binds to a specific DNA sequence close to the centromere of chromosome 21.  RFLP analysis for the child, mother, and father is shown below. In which of the following meiosis events did the nondisjunction most likely occur?

A)Maternal meiosis I
B)Maternal meiosis II
C)Paternal meiosis I
D)Paternal meiosis II

Question 30

A genetic researcher is comparing the DNA replication process of prokaryotic and eukaryotic cells.  In an experiment, Escherichia coli and human cells are cultured in separate media containing tagged nucleotides and their rates of DNA replication are determined.  Although the eukaryotic genome is significantly larger and more complex than that of the prokaryote, eukaryotic DNA replication still occurs in a timely manner.  Which of the following features of eukaryotic replication best explains this observation?

A)Continuous synthesis of the lagging strand
B)Energy-independent DNA unwinding
C)Multiple origins of replication
D)No proofreading of daughter strands
E)No requirement for RNA primers

Question 31

A researcher is studying the expression pattern of a particular gene.  Messenger RNA is isolated from several tissues, subjected to electrophoresis, blotted, and probed with radiolabeled DNA containing sequences from exon 4 from that gene.  An x-ray film is then placed over the blotting membrane, with the results of the autoradiogram shown below: Which of the following best explains the autoradiogram findings in the different tissues?

A)Alternate RNA splicing
B)DNA rearrangement
C)DNA mutation
D)Enhancer effect
E)Transcription factor effect

Question 32

A patient is suspected of having an inherited disorder.  Pedigree analysis shows the following pattern: This patient most likely has which of the following conditions?

A)Classic galactosemia
B)Hemophilia B
C)Huntington disease
D)Leber hereditary optic neuropathy
E)Rett syndrome

Question 33

A 24-year-old woman comes to the office after discovering a new mole on her right leg.  She is worried that it might be skin cancer as she has used tanning beds several times a year since age 18.  Physical examination shows a 5-mm brown, oval macule on her anterior thigh with a homogeneous coloration and discrete borders.  The lesion appears darker than her other moles.  A biopsy of the lesion shows normal-appearing nevus cells clustered in the epidermis, and she is diagnosed with a benign acquired melanocytic nevus.  During histologic analysis, her epithelial cells are each found to contain a condensed body composed of heavily methylated DNA at the periphery of the nucleus.  This region of DNA is most likely associated with which of the following genetic findings?

A)DNA supercoil accumulation
B)Extensive double-strand DNA break repair
C)Histone acetylation
D)Impaired mismatch repair
E)Low transcription activity

Question 34

A 25-year-old nulligravid woman comes with her husband to the clinic for preconception genetic counseling.  She has oculocutaneous albinism due to a homozygous OCA2 gene mutation within the region of chromosome 15q12-q13.  Examination shows pale hypopigmented skin with blonde hair.  Eye examination shows faint brown irises.  Her husband is 26 years old and has oculocutaneous albinism due to a biallelic TYR gene mutation at position 11q14.3.  Examination of the husband shows complete absence of pigmentation in the skin, hair, and irises.  The couple asks about their chance of having a child with oculocutaneous albinism and are told that the chance is 0%.  Which of the following is the best explanation for this?

A)Allelic heterogeneity
B)Heteroplasmy
C)Incomplete penetrance
D)Linkage disequilibrium
E)Locus heterogeneity
F)Pleiotropy

Question 35

A 4-year-old boy is brought to the physician for fatigue and persistent bone pain.  Physical examination shows diffuse lymphadenopathy and multiple purpura over his arms and legs.  Laboratory analysis reveals anemia and thrombocytopenia, and a peripheral blood smear shows lymphoblasts.  After further workup, he is diagnosed with acute lymphoblastic leukemia and started on a chemotherapy regimen that includes doxorubicin.  This agent intercalates between DNA base pairs and inhibits DNA replication, a process that normally occurs at sites known as replication forks.  As the replication forks move across the DNA molecule, 2 distinct daughter strands are formed.  Which of the following is unique to the daughter strand that is synthesized in the opposite direction of the growing replication fork?

A)Synthesis of multiple, short DNA fragments
B)5'→3' exonuclease activity of DNA polymerase
C)3'→5' exonuclease activity of DNA polymerase
D)3'→5' polymerase activity of DNA polymerase
E)RNA primer synthesis before DNA strand synthesis

Question 36

Geneticists are studying a malfunctioning protein that causes impaired endothelial cell migration and angiogenesis.  They have noticed that the amino acid sequence of the protein is truncated compared to normal controls.  The mutated mRNA strand is isolated, and analysis shows a nonsense mutation located near the 3' end of the coding region.  The 3' terminal coding sequence of the abnormal mRNA strand is shown below. Which of the following tRNA anticodons is responsible for adding the last amino acid to the truncated polypeptide during protein translation?

A)5'-AAC-3'
B)5'-AUC-3'
C)5'-CAA-3'
D)5'-GCU-3'
E)5'-UCG-3'

Question 37

A 56-year-old man comes to the office due to difficulty swallowing for the past several months.  He has the most trouble with solid foods and says, "They seem to get stuck in my throat if I don't chew a lot."  The patient has no chest pain or heartburn and has lost 4.5 kg (10 lb) in the last 3 months.  He has been an avid hunter for many years and frequently cures the meat he eats with sodium nitrite.  Physical examination is unremarkable.  Endoscopy shows an ulcerated mass in the distal third of the esophagus, and biopsy samples are obtained from the mass and adjacent normal mucosa.  Analysis of the samples shows accelerated cytosine deamination of chromosomal DNA in both normal and malignant epithelial cells.  This damage is most likely to be repaired through which of the following enzymatic sequences?

A)Endonuclease, polymerase, glycosylase, lyase, ligase
B)Endonuclease, polymerase, lyase, glycosylase, ligase
C)Glycosylase, endonuclease, lyase, polymerase, ligase
D)Glycosylase, ligase, lyase, endonuclease, polymerase
E)Lyase, endonuclease, glycosylase, polymerase, ligase

Question 38

A 13-year-old boy with growth retardation, microcephaly, sun-sensitive skin rash, and recurrent infections is being evaluated for a possible inherited genetic defect.  The patient is the second-born child of a first cousin marriage.  His parents and siblings are healthy, but 2 of his maternal cousins have similar signs and symptoms.  Genetic analysis of the patient reveals a defect in the BLM gene that codes for DNA helicase.  Which of the following is the most likely site of action of this enzyme in the DNA replication fork shown below?

A)A
B)B
C)C
D)D
E)E
F)F

Question 39

A pharmaceutical researcher develops a novel antibacterial drug that works by inhibiting exonuclease activity during DNA replication.  When actively dividing Escherichia coli is exposed to the drug, enzyme-mediated nucleotide removal in the 5' to 3' direction is impaired, leading to inhibition of bacterial growth.  Which of the following enzymes is the most likely target of this drug?

A)DNA polymerase I
B)DNA polymerase III
C)Gyrase
D)Helicase
E)Ligase
F)Primase

Question 40

A young couple has undergone a successful in vitro fertilization procedure.  The father has cystic fibrosis and the mother has a sister with cystic fibrosis.  The father as well as the mother's sister are both known to have ΔF508 mutations, but the mother's carrier status is unknown.  Before making the decision to conceive, the couple underwent extensive genetic counseling regarding the potential risks of having a child with cystic fibrosis.  The family pedigree is diagrammed below with the unborn child marked by the red arrow. What is the probability that the unborn child will have cystic fibrosis?

A)1/16
B)1/8
C)1/4
D)1/3
E)2/3
F)3/4

Question 41

A 23-year-old previously healthy man comes to the office after noticing a painless, hard mass in the left testis.  Scrotal ultrasound shows a solid testicular mass, and CT scan of the abdomen and pelvis shows left paraaortic lymphadenopathy.  Left orchidectomy is performed and postoperative histopathology reveals seminoma of the testis.  External beam radiotherapy is administered to the paraaortic metastatic area.  Several weeks later, the retroperitoneal nodes are observed to have markedly decreased in size.  Which of the following is the most likely effect of the therapy used on the metastatic cells in this patient?

A)Demethylation of DNA
B)DNA cross-linking
C)Double-strand DNA breaks
D)Nucleotide mismatches
E)Pyrimidine dimers

Question 42

A 12-year-old Caucasian male with history of seizure disorder experiences several stroke-like episodes with residual neurological deficit.  He also suffers from muscle weakness.  Blood tests show increased serum lactate levels both post-exercise and at rest.  This patient's condition is known to be maternally inherited.  This patient's sister is also affected by the same disorder, but she displays very few symptoms.  Which of the following is the most likely explanation for the variability in clinical presentation between the patient and his sister?

A)Genetic imprinting
B)Heteroplasmy
C)Anticipation
D)Low expression variability
E)Female sparing

Question 43

A 10-year-old boy is brought to the emergency department for new swelling in his right leg.  He has a history of lens dislocation and intellectual disability.  Physical examination demonstrates moderate, pitting edema from his right calf to his right thigh and a normal left lower extremity.  In addition, the patient has a caved-in appearing chest wall.  He has no family members with similar conditions.  Ultrasound reveals a deep venous thrombosis in his right femoral vein.  Further genetic testing reveals a single missense mutation in the gene coding for cystathionine beta-synthase enzyme.  Which of the following is the most likely explanation for this patient's genetic defect affecting multiple tissues?

A)Dominant negative mutation
B)Genetic linkage
C)Incomplete penetrance
D)Locus heterogeneity
E)Pleiotropy
F)Polyploidy
G)Segregation

Question 44

A 3-year-old boy is being evaluated for recurrent respiratory infections.  The patient's family immigrated to the United States 5 months after his birth.  Since then, the boy has experienced multiple episodes of pneumonia and bronchitis, and has developed a persistent cough and failure to thrive.  His older brother has no medical issues.  A genetic test is performed and reveals a mutation in an exon of a gene that codes for a transmembrane chloride channel.  The abnormal mRNA is isolated from cultured epithelial cells, and its complementary DNA is synthesized.  Amplified cDNA samples from both the patient and his healthy sibling are analyzed using gel electrophoresis and compared to DNA fragments of known size to determine base pair length.  The results are shown below. Which of the following is most likely responsible for this patient's condition?

A)Frameshift mutation
B)In-frame deletion
C)Missense mutation
D)Nonsense mutation
E)Silent mutation
F)Trinucleotide expansion

Question 45

A 33-year-old woman, gravida 2 para 1, comes to the office for a prenatal visit at 20 weeks gestation.  She feels well and reports experiencing fetal movements.  The patient has no medical problems other than a history of cleft lip, which was repaired in childhood.  Her husband is healthy, but her previous child was born with spina bifida.  She takes a daily prenatal vitamin.  Physical examination is unremarkable and uterine size is in accordance with ultrasound dates.  The patient is worried that the fetus may develop the same birth defect as her previous child.  Which of the following is the most likely mode of inheritance of this disorder?

A)Autosomal dominant
B)Autosomal recessive
C)Mitochondrial
D)Multifactorial
E)X-linked recessive

Question 46

A healthy couple, who recently emigrated from Eastern Europe, bring their 3-year-old son to the office for evaluation of an eczematous rash.  On examination, the child also shows signs of intellectual disability and gait abnormality and has a musty body odor.  What is the likelihood that this couple's next child will be affected with the same disease?

A)Same as the general population
B)1/32
C)1/16
D)1/8
E)1/4
F)1/2

Question 47

A 58-year-old man comes to the office with a persistent dry cough.  He has experienced an involuntary weight loss of 10 kg (22 lb) over the last 3 months.  The patient drinks 2-3 beers daily and has a 40-pack-year smoking history.  Physical examination shows dullness to percussion over the right lower lung base.  A chest CT reveals a right-sided pleural effusion and a mass in the lower lobe of the right lung.  Transbronchial biopsy of the mass demonstrates malignant cells with large nuclei that contain prominent, round, basophilic bodies as shown below. Which of the following enzymes is most likely to function only within this basophilic region of the nucleus?

A)DNA endonuclease
B)DNA polymerase
C)RNA polymerase I
D)RNA polymerase II
E)RNA polymerase III

Question 48

A 50-year-old previously healthy man is evaluated for progressive fatigue, weakness, and recurrent gingival bleeding.  Laboratory studies reveal normocytic normochromic anemia, thrombocytopenia, and leukocytosis with circulating myeloblasts.  Bone marrow biopsy establishes a diagnosis of acute myeloid leukemia.  Induction chemotherapy followed by allogeneic hematopoietic cell transplantation (HCT) is planned.  Molecular typing of human leukocyte antigen (HLA) -A, -B, -C, -DP, -DQ, and -DR is performed.  The patient's biological sister, with whom he shares both parents, is eligible for stem cell donation and undergoes HLA typing.  Which of the following is the most likely probability that the sibling will be an identical HLA match with this patient?

A)0
B)1/16
C)1/8
D)1/4
E)1/2

Question 49

A 26-year-old woman comes to the office for follow-up.  The patient and her husband want to have a child, and she inquires about the risk of certain genetic conditions, including cystic fibrosis (CF).  The patient is from a small city with a stable Caucasian population, where the carrier frequency for CF is 1/30 Caucasian individuals.  Her husband is from a nearby community, where CF carrier frequency in individuals of Asian descent is 1/100.  Both the patient, who is Caucasian, and her husband, who is of Asian descent, are healthy.  What is the probability that a child born to a mother from the Caucasian community and a father from the Asian community will have the disease?

A)1/900
B)1/1,000
C)1/3,000
D)1/6,000
E)1/12,000

Question 50

A 28-year-old man is evaluated for abnormal movements of the hands and face.  The patient reports that he started experiencing involuntary grimacing a year ago, which has gradually worsened.  He is taking a selective serotonin reuptake inhibitor for major depression but has not taken any antipsychotic medications.  His 52-year-old father was diagnosed with an inherited movement disorder 2 months ago.  Physical examination shows normal strength and normal deep tendon reflexes.  No sensory deficits are noted.  Which of the following best explains the difference in disease presentation between this patient and his father?

A)Anticipation
B)Genomic imprinting
C)Incomplete penetrance
D)Microdeletion
E)Mosaicism
F)Pleiotropy

Question 51

A 46-year-old woman is evaluated for a 2-month history of progressive abdominal distension, vague abdominal discomfort, and a bloating sensation.  Physical examination shows moderate ascites.  Laboratory evaluation reveals markedly elevated CA-125 and imaging studies show an ovarian mass.  Molecular analysis of the malignant cells in ascitic fluid is performed, and these cells are found to have high telomerase activity.  This enzyme promotes cell growth and malignancy by directly causing which of the following actions?

A)Enhancing tissue invasion and metastasis
B)Increasing transcription factor expression
C)Preventing chromosomal shortening
D)Promoting G1/S progression
E)Sustaining angiogenesis

Question 52

Molecular biologists are investigating the functional significance of non-coding RNA molecules.  During an experiment, they isolate large complexes containing both protein and RNA from exocrine pancreatic cells.  The complexes are found both freely floating in the cytoplasm and bound to the endoplasmic reticulum.  The RNA found within these complexes is primarily synthesized at which of the following intracellular sites?

A)A
B)B
C)C
D)D
E)E

Question 53

A study is undertaken to map the HLA-DQ loci in a population with a high incidence of celiac sprue.  High-resolution HLA typing of the DQA1 and DQB1 loci is performed using polymerase chain reaction sequencing.  The frequency of the DQA1*0501-DQB1*0201 haplotype, strongly implicated in autoimmunity, is found to be 0.2.  However, in the same population, the frequency of the DQA1*0501 allele is 0.3 and the frequency of the DQB1*0201 allele is 0.2.  Which of the following best explains the observed DQA1*0501-DQB1*0201 haplotype frequency in this population?

A)Heteroplasmy
B)Increased penetrance
C)Linkage disequilibrium
D)Pleiotropy
E)Segregation

Question 54

In an experiment, cultured fibroblasts are mechanically lysed, and the membrane lipids and cellular proteins are chemically removed to isolate nucleic acids.  The cellular extract containing the purified nucleic acids is incubated along with short sequences of repeated deoxythymidine residues fixed to latex beads.  The solution is washed several times to remove unbound molecules.  Which of the following types of nucleic acid is most likely to bind the strongest to the latex beads in this experiment?

A)Aminoacyl-tRNA
B)Mature mRNA
C)Promoter regions of DNA
D)Ribosomal RNA
E)Splice sites of pre-mRNA
F)Telomere regions of chromosomes

Question 55

A 26-year-old woman comes to the office with her husband for genetic counseling.  She is pregnant with their second child, whose gender is unknown.  Both parents are asymptomatic, but their firstborn 3-year-old son has recurrent episodes of anemia, jaundice, and painful swelling of the hands and feet.  A blood sample is obtained from the boy, and hemoglobin electrophoresis is performed at alkaline pH.  The results are shown in the image below. What is the probability that the unborn child will inherit one or more mutant alleles from the parents?

A)Near 0
B)25%
C)50%
D)75%
E)100%

Question 56

A 19-year-old woman is evaluated for new onset generalized tonic-clonic seizures.  For the past several years, she has also been having erratic jerks of her arms and legs, and intermittent muscle weakness.  The girl has multiple family members with similar symptoms.  Neurological examination reveals decreased sensation in the lower extremities and a broad-based gait.  Skeletal muscle biopsy shows ragged, red-appearing muscle fibers.  Further analysis reveals that the patient's symptoms are due to a mutation affecting extranuclear DNA.  Which of the following pedigrees is most likely to represent this patient's family history? (The arrow points to the patient.)

A)
B)
C)
D)
E)

Question 57

A 5-year-old boy is being evaluated for progressive muscle weakness that has resulted in numerous recent falls.  There is no family history of muscle disorders.  Physical examination reveals bilateral calf enlargement.  When the patient is asked to stand, he uses his hands and arms to help push himself to an upright position.  Serum creatine kinase is 12,600 U/L (normal: 30-170 U/L).  Molecular tests reveal a large muscle protein that is defective due to the loss of 508 amino acid residues.  Genetic analysis reveals a single base substitution within exon 48 of the gene encoding this muscle protein.  This patient's gene mutation has most likely resulted in which of the following mRNA codon changes?

A)CUU → AUU
B)UAA → UAG
C)UAC → CAC
D)UCA → UGA
E)UUU → UUC

Question 58

A 43-year-old man is evaluated for progressive neuropsychiatric symptoms.  A year ago, he began feeling depressed and having hallucinations.  Five months later, he developed intermittent paresthesias and progressively worsening choreiform movements, myoclonus, and ataxia.  These symptoms have not improved despite multiple hospitalizations; an extensive workup has been unrevealing.  The patient is a slaughterhouse worker with extensive exposure to bovine offal.  As part of the evaluation for prion disease, a tissue sample digested with protease is processed via gel electrophoresis and transferred to filter paper.  Antibodies to a specific prion protein are added to the filter.  Next, a marked protein that combines with the antibody-protein complex is used to determine whether the test is positive.  Which of the following best describes this test?

A)Microarray
B)Northern blot
C)Southern blot
D)Southwestern blot
E)Western blot

Question 59

A researcher develops 2 functional mRNA sequences composed of CUC and CUU trinucleotide repeats, respectively.  He subsequently incubates these mRNAs in a solution containing functional ribosomes and tRNAs charged with the appropriate amino acids.  After several hours, it is found that both mRNA sequences produce polypeptide chains containing leucine repeats.  This observed finding is due to which of the following genetic principles?

A)Ambiguity
B)No punctuation
C)Transition
D)Universality
E)Wobble

Question 60

A 34-year-old woman comes to the office due to dysuria.  The patient has a history of recurrent urinary tract infections.  A urine sample is collected and sent for culture.  Gram-negative bacteria isolated from the urine are found to form pink colonies on lactose-containing MacConkey agar.  Several days later, bacterial isolates from a second urine sample are found to form white colonies when plated on the same type of medium.  Genetic analysis shows that the more recent isolates have a single nucleotide deletion within the lac operon DNA sequence.  This genomic change is most consistent with which of the following?

A)Conservative mutation
B)Frameshift mutation
C)Missense mutation
D)Nonsense mutation
E)Silent mutation

Question 61

In an experiment, erythrocyte precursor cells are incubated in a medium containing radiolabeled cysteine.  These radiolabeled cysteine residues are attached to their appropriate tRNAs by the enzyme aminoacyl-tRNA synthetase.  The bound cysteine residues are then chemically modified to form alanine.  The end product of this reaction is a tRNA molecule that contains the cysteine anticodon but is mischarged with alanine.  Which of the following is most likely to occur to this alanine residue during polypeptide synthesis of alpha-hemoglobin?

A)It will be incorporated into the polypeptide chain at a site requiring alanine
B)It will be incorporated into the polypeptide chain at a site requiring cysteine
C)It will be randomly incorporated into the polypeptide chain, halting chain elongation
D)It will be rapidly cleaved off tRNA by the enzyme glycosylase
E)It will never be incorporated into the polypeptide chain and will remain attached to tRNA

Question 62

A 24-year-old African American woman comes to the office with her husband for prenatal counseling.  She has a 3-year-old child with sickle cell anemia from a previous marriage, and the child's father died in a car accident.  The patient remarried last year and is interested in having more children.  She and her new husband do not have sickle cell anemia, and the patient's husband has no other children.  However, the patient and her husband are worried that their future children could have sickle cell anemia.  A urine pregnancy test is negative.  Which of the following is the best initial test that can be offered to this couple?

A)Chorionic villous sampling during future pregnancy
B)Maternal hemoglobin electrophoresis
C)Northern blot analysis of paternal blood sample
D)Paternal hemoglobin electrophoresis
E)Paternal karyotype analysis

Question 63

A 6-year-old boy is brought to the office due to a persistent facial ulcer for the past 2 months.  His mother reports that the patient has extreme sensitivity to sunlight and has developed freckles on his face, neck, and limbs since infancy.  On physical examination, the skin in sun-exposed areas is dry and rough with numerous freckles and erythematous macules.  There is an ulcerated plaque on the left face; a biopsy reveals squamous cell carcinoma.  Further testing leads to a diagnosis of xeroderma pigmentosum.  A defect in which of the following enzymes is most likely causing this patient's condition?

A)3'→5' exonuclease
B)DNA ligase
C)Endonuclease
D)Helicase
E)Topoisomerase

Question 64

An 8-year-old boy of Ashkenazi Jewish ancestry is brought to the office after developing reduced sensitivity to pain, impaired tear formation, and orthostatic hypotension.  Familial dysautonomia is suspected due to the patient's symptoms and heritage.  This disorder is caused by loss of function of the IKAP protein, which is essential for development and survival of sensory and autonomic neurons.  IKAP gene sequencing reveals a single nucleotide substitution that causes a guanine residue to be replaced by adenine at the highlighted position in the normal gene sequence shown below.  Exon sequences are represented by capital letters and introns by lowercase letters. Which of the following is the most likely effect of this mutation?

A)Decreased mRNA export to the cytosol
B)Impaired ribosomal attachment to mRNA
C)Incorrect splicing of pre-mRNA
D)Increased degradation of mRNA by 5' exonucleases
E)Translation of the 3'-untranslated region of mRNA

Question 65

A 16-year-old girl with a history of anemia since childhood is evaluated for a genetic abnormality after several members of her family are also found to be anemic.  It is determined that she has a point mutation in the β globin gene, which has resulted in the substitution of guanine (G) with cytosine (C) in the mRNA sequence shown below (+1 position indicates start codon). Which of the following cellular processes is most likely impaired due to this patient's gene mutation? A)Co-translational protein targeting to endoplasmic reticulum B)Initiation of translation C)Peptide bond formation D)Ribosomal translocation during polypeptide elongation E)Termination of polypeptide synthesis

Question 66

An 18-year-old man comes to the urgent care clinic due to painful erythema affecting his extremities, trunk, and face.  He is vacationing in Florida and spent 5 hours at a Gulf coast beach earlier in the day.  The patient did not apply any sunscreen as it was cloudy.  The physician explains that cloud cover does not afford a high degree of protection against the sun, especially with prolonged exposure in highly reflective environments like the beach.  He is advised to wear protective clothing and apply sunscreen to prevent recurrence.  Which of the following is most likely to happen within the patient's skin cells as a result of his exposure?

A)Covalent bond formation between adjacent purine bases
B)End-joining repair of double-stranded DNA breaks
C)Endonuclease nicking of the damaged DNA strand
D)Hypermethylation of residues in the undamaged DNA strand
E)Removal of deaminated bases by glycosylase

Question 67

A series of experiments is being conducted to determine the structure and function of different types of bacterial RNA.  Cultures of Staphylococcus aureus are exposed to chemicals that lyse the bacterial cells, and the RNA molecules are then extracted.  A specific RNA consisting of 90 nucleotides is purified for further analysis.  It is found to contain high amounts of chemically modified bases such as dihydrouridine, pseudouridine, and ribothymidine, and its secondary structure arises from base pairing within the chain.  Which of the following is the most likely composition of the 3'-end of this molecule?

A)AUG
B)CCA
C)Methylguanosine triphosphate
D)Poly-A
E)TATA
F)UAG

Question 68

A 12-year-old boy is evaluated in the clinic due to excessive bleeding following a tooth extraction.  The patient also develops large bruises after only minor injury but has had no major bleeding episodes in the past.  His maternal uncle died from an intracranial hemorrhage.  Laboratory testing reveals decreased coagulation factor VIII activity levels.  A referral is made to a clinical geneticist, who suspects that the patient has a deletion mutation in the enhancer sequence of the factor VIII gene.  This mutation has resulted in decreased transcription of factor VIII by RNA polymerase II.  Which of the following is the most accurate statement regarding the abnormal genetic sequence in this patient?

A)It can be located upstream, downstream, or within introns of the gene
B)It can function within only a short distance of the gene
C)It directly binds RNA polymerase and general transcription factors
D)It does not require protein binding to affect transcription
E)It is required to initiate transcription

Question 69

A pharmaceutical researcher is evaluating a nuclear enzyme inhibitor for the treatment of an inherited disorder.  During an experiment, he extracts and purifies nuclear enzymes from skin cells of an affected patient.  One of these enzymes is found to catalyze the methylation of cytosine residues in DNA using S-adenosyl-methionine (SAM) as the methyl donor.  This enzyme most likely plays a crucial role in which of the following genetic processes?

A)Aneuploidy
B)Epistasis
C)Imprinting
D)Meiotic nondisjunction
E)Pleiotropy

Question 70

A pharmaceutical researcher performs preclinical testing on a novel chemotherapeutic drug.  When rat embryos are exposed to this drug during an early stage of organogenesis, they develop severe skeletal malformations.  Further genetic analysis reveals that the drug causes mutations in numerous homeobox genes containing highly conserved 180 base pair DNA sequences.  The genes affected by this drug most likely code for which of the following proteins?

A)Cell surface receptors
B)Cytoplasmic enzymes
C)DNA replication enzymes
D)Structural proteins
E)Transcription regulators
F)Transport proteins

Question 71

A geneticist is performing an experiment to alter protein structures by incorporating modified amino acids into their polypeptide sequences.  During the process, she incubates dermal fibroblasts in a medium containing fluorescently labeled lysine residues.  After several hours, she finds that aminoacyl tRNA synthetase in the fibroblasts "loads" lysine residues onto tRNA molecules containing the anticodon UUU.  This residue most likely attaches to tRNA at which of the following sites in the image shown below?

A)A
B)B
C)C
D)D
E)E
F)F

Question 72

A genetic study performed on a 10-year-old boy reveals a single base substitution mutation involving a DNA segment that encodes a cellular protein, as shown in the image below. This mutation is most likely to affect which of the following processes?

A)DNA methylation
B)Polypeptide folding following translation
C)Posttranscriptional RNA splicing
D)RNA elongation
E)Transcription initiation
F)Translation initiation

Question 73

A 14-year-old boy with chronic anemia is being evaluated after experiencing several episodes of chest, back, and extremity pain.  Peripheral blood smear shows sickle-shaped red cells.  Genetic testing reveals that the patient is homozygous for a point mutation in the beta-globin gene, resulting in a glutamic acid to valine substitution at position 6.  Sequencing of the beta-globin gene would most likely reveal which of the following changes? (The genetic code is shown in the figure below.)

A)CAA → GTT
B)CAT → CTT
C)TTA → CTA
D)GAA → GUA
E)GAG → GTG
F)GTA → GAA

Question 74

A pharmaceutical corporation investigating new therapeutic agents for treatment of Burkitt lymphoma synthesizes a double-stranded RNA molecule that is 21 base pairs in length.  The RNA molecule has a base pair sequence that is complementary to a region of mRNA encoding c-Myc.  Introduction of the RNA molecule into tumor cells results in a significant reduction in cell growth.  Western blot analysis of equivalent numbers of treated and untreated cells is shown below. Which of the following processes was most likely directly interrupted in the cells exposed to the RNA molecule?

A)DNA replication
B)DNA transcription
C)mRNA translation
D)Proteasome activity
E)Splicing

Question 75

A 5-year-old girl is brought to the office by her mother because she is concerned that her daughter "sunburns too easily."  The mother says the patient's skin becomes red and scaly with only minimal sun exposure.  She first noticed the problem when her daughter was 7 months old during a trip to the beach.  The mother has since avoided exposing her child to excess sunlight, but finds it difficult now that the patient has begun kindergarten.  Physical examination shows thin and hyperpigmented skin.  She also has a few nevi on her hands that have been enlarging rapidly.  This patient's disorder is most likely due to a primary defect involving which of the following processes?

A)DNA mismatch repair
B)Nucleotide excision repair
C)Ras signal transduction
D)Regulation of apoptosis
E)Regulation of cell cycle
F)Repair of DNA crosslinks

Question 76

A pharmaceutical researcher develops a new drug that affects bacterial protein synthesis.  In an experiment, Escherichia coli is exposed to the drug and serially cultured in media containing tagged nucleotides and amino acids.  It is found that the drug inhibits molecules that recognize the highlighted codon in the bacterial mRNA fragment shown in the image below. Which of the following molecules is the most likely target of this drug?

A)Charged tRNA
B)Elongation factor 2
C)Releasing factor 1
D)snRNP
E)Transcription factor II D
F)Uncharged tRNA

Question 77

A 32-year-old man is recovering from extensive burns.  Fibroblasts near the site of injury actively synthesize precursor mRNA to be used as templates for protein synthesis.  After transcription, extensive processing of the precursor RNA occurs to form the finalized mRNA sequence.  The finalized mRNA then exits the nucleus and undergoes translation by ribosome complexes before being degraded.  Which of the following steps involving the processing and handling of mRNA occurs only within the cytoplasm of cells?

A)5'-terminal guanosine triphosphate addition
B)Methylation of the 5'-terminal guanine
C)Multiple adenine nucleotide attachment to the 3'-end
D)Interaction with snRNP
E)Removal of intervening sequences
F)Interaction with P bodies

Question 78

A researcher is studying the Fas receptor (FasR), a protein widely expressed on cell surfaces.  The signaling cascade of programmed cell death is initiated when FasR binds to its ligand (FasL), which is expressed on cytotoxic T cells.  In an experiment, cancer cells that escaped elimination by the immune system were found to contain soluble Fas proteins that did not promote apoptosis.  The soluble Fas proteins were shorter and lacked the transmembrane domain.  DNA analysis of these cells revealed no FAS gene mutations.  Which of the following is the most likely explanation for the formation of altered Fas proteins in these cancer cells?

A)Alternative splicing
B)Defective polyadenylation
C)DNA methylation
D)Polycistronic mRNA
E)Protein ubiquitination

Question 79

A 7-year-old boy is admitted to the hospital after his adoptive parents brought him to the emergency department due to fatigue and pallor.  Laboratory evaluation reveals pancytopenia with an absolute neutrophil count consistent with severe neutropenia.  Bone marrow examination reveals signs of aplastic anemia, and subsequent genetic testing reveals a congenital genomic defect in DNA repair leading to chromosomal instability.  A bone marrow transplant is required for treatment.  The patient's only living relatives are an identical twin brother and older sister who were both adopted by the same parents.  He also has stored umbilical stem cells that were harvested after birth.  Which of the following is the best bone marrow transplantation method for this patient?

A)Freshly harvested autologous transplant
B)Matched unrelated donor
C)Stored umbilical cord stem cells from the patient
D)Twin sibling syngenetic transplant
E)Unmatched sibling allogeneic transplant

Question 80

A 6-year-old girl with chronic anemia requiring repeated blood transfusions is undergoing genetic testing.  The patient's mother and older sibling have a history of mild anemia.  Her peripheral blood smear shows hypochromic, microcytic red blood cells, and hemoglobin electrophoresis reveals a predominance of hemoglobins F and A2.  Sequencing of the β-globin gene is performed using the patient's erythroblast DNA.  A schematic representation of the gene and its transcribed RNA is shown in the image below. The base sequence indicated by the bold red arrow is responsible for which of the following functions?

A)Enhancement of transcription
B)Initiation of transcription
C)Initiation of translation
D)Repression of transcription
E)Termination of transcription