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 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?

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 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 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 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 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?

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 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 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 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?

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 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 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 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 lysate 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?

Item 2 of 2

The patient’s genetic defect has resulted in decreased β globin chain synthesis.  Which of the following is most likely to be seen on laboratory testing?

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).

Item 1 of 2

Which of the following cellular processes is most likely impaired due to this patient’s gene mutation?

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 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?

Researchers studying chronic lymphocytic leukemia (CLL) observe that in some patients the disease is indolent, with limited growth over more than a decade, whereas in other patients the disease is more aggressive and becomes symptomatic early on.  They find that genetic abnormalities can be detected in a majority of patients with CLL and may play a role in determining the difference between the 2 disease courses.  A clinical study is conducted with the hypothesis that individuals with CLL with trisomy of chromosome 12 have a more favorable course than individuals with other genetic changes.  Which of the following laboratory techniques would be most useful for identifying patients with this genetic abnormality?

A 34-year-old woman comes to the office after her sister was diagnosed with breast cancer.  She has no nipple discharge, breast lumps, or discomfort.  Breast examination is normal.  Her sister was found to have a multiple base pair insertion affecting exon 11 of the BRCA1 gene that leads to a frameshift mutation.  A screening test to evaluate for a similar insertion mutation in the patient’s BRCA1 gene is performed.  The test uses polymerase chain reaction (PCR) to amplify the target exon and gel electrophoresis to assess the size of the exon compared to the wild-type allele.  Which of the following must be known in order to perform the amplification part of this analysis?

A researcher is studying the structure of different hormone receptors.  Receptor proteins are isolated and purified from a homogenized tissue sample.  Detailed structural analysis shows that one of the proteins contains a 30-amino acid motif coordinating a zinc molecule, as shown in the image below.

A receptor for which of the following hormones was most likely isolated in this experiment?

A 54-year-old man comes to the emergency department with a 3-month history of fatigue and exertional dyspnea.  He has early satiety and frequent upper abdominal discomfort.  On physical examination, the patient has palpable splenomegaly but no lymphadenopathy.  Laboratory tests are as follows:

Reverse transcription polymerase chain reaction is used to diagnose chronic myelogenous leukemia in this patient.  Which of the following is most likely to be detected by this test?

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?

Researchers are working to identify new targets for drug development to treat idiopathic pulmonary fibrosis.  After obtaining lung tissue samples from affected patients, they conduct a series of experiments to measure the expression and activity of various profibrotic proteins.  The results for one such protein, galectin-3, are as follows:

Which of the following processes best explains these findings?

Researchers analyzing eukaryotic genome structure and function perform an experiment to extract DNA from exocrine pancreatic cells.  During the purification process, they isolate small circular DNA molecules that resemble a bacterial chromosome.  Further analysis shows that these molecules code for proteins, transfer RNA, and ribosomal RNA.  From which of the following cellular structures did these DNA molecules most likely originate?

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?