Quiz 12: The Molecular, Biochemical, and Cellular Basis of Genetic Disease

If an infant is found to have hyperphenylalaninemia based on a newborn screen, but this defect doesn't respond to a low phenylalanine diet, what type of molecular defect would be suspected? A) Null mutation for phenylalanine hydroxylase B) Dominant negative mutation for phenylalanine hydroxylase C) A defect in tetrahydrobiopterin (BH₄) metabolism D) A mutation in tyrosine hydroxylase E) A mutation in tryptophan hydroxylase

Which patients with mutations in phenylalanine hydroxylase are most likely to respond to BH₄ supplementation? A) Those with null mutations B) Those who have only one phenylalanine hydroxylase (PAH) mutation C) Those who are compound heterozygotes for PAH mutations D) Those with residual PAH activity E) Those with a defect in BH₄-PAH binding

What observation has facilitated genetic testing for Tay-Sachs disease in the Ashkenazi Jewish population? A) Three mutations account for the vast majority of disease alleles B) The causative gene is small C) There are no pseudo-disease alleles D) Only missense mutations cause disease E) Only nonsense mutations cause disease

Where are GM2 ganglioside and mucopolysaccharides digested? A) Proteasome B) Endosome C) Lysosome D) Extracellularly E) Cytoplasm

The finding that fibroblasts from a patient with X-linked Hurler syndrome could correct the defect in fibroblasts from a patient with autosomal recessive Hurler syndrome (and vice versa) demonstrated what about the two disorders? A) There is a mild phenotype in either case B) One form of Hurler is more severe than the other C) Different proteins were deficient in the two disorders D) The same protein was deficient in the two disorders E) One was caused by a missense mutation and the other by a nonsense mutation

Which of the following properties allows enzyme replacement therapy to work for some lysosomal storage disorders? A) Excess enzyme causes formation of new lysosomes B) The enzymes can be dried into a pill C) The enzymatic defect is generally mild D) Cells can take up the enzymes from extracellular fluid E) The therapy triggers upregulation of the deficient enzyme

Why can vitamins be used to treat some enzymatic defects? A) They are water-soluble B) They can increase the activity of the defective enzyme C) They often serve as enzyme cofactors D) They can sometimes stabilize the defective enzyme E) All of the above

Genetic defects that impair the activity of methionine synthase are mimicked by a dietary deficiency of which vitamin? A) Vitamin C B) Vitamin A C) Vitamin B₁₂ D) Vitamin D E) Vitamin K

What inheritance pattern is most common for metabolic disorders? A) Autosomal dominant B) Autosomal recessive C) X-linked dominant D) X-linked recessive E) None of the patterns predominates

How can a single gene defect lead to multiple enzyme deficiencies? A) The enzymes share a cofactor B) The enzymes are modified by the same processing pathway C) The enzymes are transported in similar ways D) The organelle in which the enzymes work is defective E) Any of the above

a1-antitrypsin deficiency leads to excess activity of which enzyme? A) Elastase B) Trypsinase C) A glycosylase D) Cystathionase synthase E) -L-iduronidase

What environmental exposure greatly influences the life expectancy of individuals with the ZZ genotype for a1-antitrypsin deficiency? A) Low folic acid intake B) Cigarette smoking C) Excess sunlight exposure D) Low fiber intake E) Alcohol intake

The genes associated with familial hypercholesterolemia all have an effect on which protein? A) Apolipoprotein E (ApoE) B) Amyloid precursor protein C) Apolipoprotein C-I D) Low-density lipoprotein (LDL) receptor E) Sterol regulatory element-binding protein

Variation in which familial hypercholesterolemia-causing gene has also been associated with protection from coronary artery disease and high cholesterol levels in general populations? A) LDL receptor (LDLR) B) PCSK9 protease C) Apoprotein B-100 (ApoB100) D) ARH adaptor protein (ARH) E) All of the above

Which of the following phenotypes is found in people with mutations in cystic fibrosis transmembrane conductance regulator (CFTR)? A) Cystic fibrosis B) Congenital bilateral absence of the vas deferens C) Idiopathic chronic pancreatitis D) Meconium ileus E) Any or all of the above

Which of the following is the major cause of chronic pulmonary infection in individuals with cystic fibrosis? A) Pseudomonas aeruginosa B) Influenza C) Common cold D) Clostridium difficile E) Francisella tularensis

Which of the following is the most common CFTR mutation in white populations? A) Arg117His B) Gln1412X C) IVS10 G>A -1 D) F508 E) 2 BP Ins, 1154TC

Mutations in the dystrophin gene cause which phenotype? A) Duchenne muscular dystrophy B) Becker muscular dystrophy C) Congenital bilateral absence of the vas deferens D) Both A and B E) Both A and C

What phenomenon has a large effect on the phenotype of female carriers of dystrophin mutations? A) Imprinting B) X-inactivation C) Expression of sex-specific modifier genes D) The lower muscle mass in females E) All of the above

In contrast to mutations associated with Duchenne muscular dystrophy, what is a feature of the mutations associated with Becker muscular dystrophy? A) They are found mostly in the 5' region of the gene B) They are found mostly in the 3' region of the gene C) They are unlikely to be deletions D) They are associated with some production of the dystrophin protein E) They are always point mutations

Which of the following leads to the higher frequency of inherited Becker muscular dystrophy compared to Duchenne muscular dystrophy? A) Higher fitness of mutations in males affected with Becker than Duchenne muscular dystrophy B) Higher mutation rate for Duchenne-associated disease C) Increased frequency of prenatal termination for Duchenne cases D) Lower penetrance in female carriers for Becker versus Duchenne mutations E) None of the above

Mutations in the genes for which major structural protein of bone and other fibrous tissues is mutated in osteogenesis imperfecta? A) Fibrin B) Actin C) Type I collagen D) Myosin E) Dystrophin

Which of the following is the only residue that can fit into certain portions of the triple helical segment of collagen because of its small size? A) Alanine B) Glycine C) Proline D) Aspartic acid E) Lysine

Which type of mutation is likely to be associated with a milder osteogenesis imperfecta phenotype? A) Missense mutation for glycine in pro₁(1) chain B) Missense mutation for glycine in pro_1) chain C) Missense mutation in either chain disrupting rate of  helix formation D) Mutation affecting posttranslational modification of collagen E) Null mutation for pro₁(1) chain

What is the likely cause when a family has two children affected with osteogenesis imperfecta type II? A) Autosomal dominant mutation in family B) Germline mosaicism in parent C) Recurrent mutation D) Increased penetrance in family E) Skewed X-inactivation

What common effect do mutations that are associated with monogenic forms of Alzheimer disease typically have? A) Increased production of Tau B) Increased production of amyloid precursor protein C) Decreased production of amyloid precursor protein D) Increased production of A₄₂ peptide E) Decreased production of A₄₂ peptide

Which of the following is true for the association of ApoE and Alzheimer disease? A) 4 is over-represented in samples of affected individuals B) 4 is associated with an earlier age of onset C) Genetic screening for the 4 allele is performed to identify those at risk of Alzheimer disease D) A and B E) All of the above

Why is maternal inheritance observed with mitochondrial DNA? A) The sperm mitochondria are eliminated from the embryo B) Sperm lack mitochondria C) Female cells have more mitochondria than male cells D) No mitochondrial genes are encoded on the paternal genome E) There is imprinting of the mtDNA

What feature of oogenesis can greatly influence the level of mtDNA mutation in the offspring of a woman carrying a mtDNA mutation? A) The small number of mitotic divisions B) The long time that elapses between the beginning and end of meiosis in females C) The mitochondrial genetic bottleneck D) Energy requirements in the egg mean natural selection has a strong effect on mitochondrial (mtDNA) mutations E) mtDNA deletions have low fitness in the egg

The tissues that are most affected by mtDNA mutations have high requirements for which of the following? A) Free radicals B) Protein C) Macromolecular transport D) Metabolic energy E) Blood flow

What is the histopathologic phenotype associated with mitochondrial myopathy? A) Ragged red fibers B) Excess mitochondria in muscle cells C) Pseudohypertrophy D) Protein inclusions E) Myelin sheath hypertrophy

What is the mechanism thought to be responsible for the expansion of trinucleotide repeats? A) Nonhomologous recombination B) Segmental duplication C) Slipped mispairing during DNA replication D) Resolution of tangled secondary structure E) Polymerase stuttering

CGG expansions in the 5' untranslated region 5'UTR of FMR1 cause which of the following? A) Expression of polyglutamine sequences B) Repeat methylation and transcriptional silencing C) Gain of function toxicity of the FMR1 mRNA D) A or B E) B or C

What is the likely mechanism by which repeat expansions cause myotonic dystrophy? A) Expression of polyglutamine sequences B) Repeat methylation and transcriptional silencing C) Translational silencing by the repeat D) Expanded repeats sequester excessive amounts of RNA-binding proteins E) C and D