Blue Boxes

Question 1

• cholesterol-uptake disrupted
• elevated LDL
• defect in gene for LDL receptor
• leads to atherosclerotic plaques

Answer 1

Familial hypercholesterolemia

Question 2

• defect in peroxisomes (absent or reduced #)

- congenital

Answer 2

Zellweger spectrum disorders

Question 3

Defect in transcription-coupled repair
mutations in ERCC6 and ERCC8
 Growth retardation, skeletal abnormalities, sensitivity to sunlight
 RNA polymerase is permanently stalled at sites of damage in important genes

Answer 3

Cockayne’s Syndrome

Question 4

• lack 3’OH
• converted to dNTPs -> inhibit DNA replication
  ex:
• arabinosylctosine (ara-C, cytarabine) –> leukemia therapy
• acyclovir
• azidothymidine (AZT) –> HIV therapy

Answer 4

nucleoside analog inhibitors

Question 5

skin is sensitive to light –> melanomas, carcinomas

–> thymidine dimers in DNA (cannot fix these due to defective NER complex)

Answer 5

xeroderma pigmentosum

Question 6

mutation in MER complex
increased susceptibility to colorectal cancers
acquired mutation in good copy of gene -> MER system nonfunctional -> tumor development

Answer 6

hereditary nonpolyposis colorectal cancer

Question 7

mutation in tumor suppressor genes (BRCA)

–> higher risk for other cancers

Answer 7

BRCA associated breast cancer

Question 8

missense mutation in B-globulin of Hb (Glu -> Val)
(- charged -> hydrophobic branched AA)
change in Hb conformation –> aggregate/rigid rod-like structures -> poor O2 carrying capacity -> clog capillaries -> poor O2 supply to tissues

Answer 8

sickle cell anemia

Question 9

X-linked, recessive -> mutation in muscle protein dystrophin (stabilizes the membrane w/ Ca2+ handling) –>
muscle wasting

Becker MD is a milder version

Answer 9

Duchenne Muscular Dystrophy

Question 10

abnormal ptn: amyloid beta peptide (AB) -> AB plaques in the brain *extracellular

hyperphosphorylation of Tau (neurofibrillary tangles) *intracellular

symptoms:
- loss of memory, cognitive function, language

Familiar form: APP, Tau
Sporadic form: aging disease

Answer 10

Alzheimer’s disease

Question 11

Parkinson’s disease

Answer 11

Abnormal ptn: a-synuclein (AS) forms insoluble fibrils -> Lewy bodies in dopa neurons in substantia nigra -> death of these neurons -> red. availability of dopamine

symptoms:
impairment of fine motor control

Familiar form: AS mutations
Sporadic form: aging

Question 12

Huntington’s disease

Answer 12

Abnormal ptn: mutation in Huntington gene -> CAG repeats -> polyglutamine repeats -> intramolecular H-bonds -> misfold, aggregate -> death of basal ganglia cells

Symptoms: loss of movement and cognitive functions, psychiatric problems

*detected w/ VNTP (variable # tandem repeats)

Question 13

Crutzfeldt-Jacob disease

Answer 13

Abnormal ptn: prion ptns, part of Transmissible spongiform encephalopathies (TSEs)

Symptoms: failing memory, behavior changes, lack coordination, visual disturbances
mental deterioration, blindness, weakness, coma

Question 14

used in cancer treatments

ex: Etoposide, Fluoroquinolones

Answer 14

topoisomerase inhibitors

Question 15

cross-linking agent -> prevents DNA replication/transcription
contains platinum ions
binds to plasma ptns -> concentrates in liver, kineys, intestine, and ovaries -> excreted in urine
* used for solid tumors

Answer 15

Cisplatin