BS Hard-to-Remember updated 6/9

Arrow = SMOOTH ER (SER) = network of

membranous sacs, vesicles + tubules continuous
with the RER but lacking ribosomes

* enzymes involved in biosynthesis of

phospholipids, TGs, sterols (e.g. steroid hormones)
ABUNDANT IN CORPUS LUTEUM active
synthesizers female sex hormones
ADRENALS (steroid hormone synth)
*detox rxns (glycogen degredation,
gluconeogenesis, lipoprotein particle assembly)
lots in liver
MT: 9 doublets + 2 (ciliary axoneme) +2 dynein arms)
RER ("parallel arrays of membrane-
Bound cisternae populated with
multiple electron-dense dots

Cell undergoing mitosis

(HETEROCHROMATIN condensed, tightly
wrapped around histones vs. loosely-packed
transcriptionally active euchromatin)

1. Gene X is on opposite strand sequence will run in

opposite direction

2. start codon ATP7B is "near first exon gene X"

5'UTR region ATP7B gene is thus either
immediately upstream of its translation start codon
or immediately downstream gene X exon 1
st
opposite Gene X 1 intron (see below)

Different receptor types

ARTERIOLlongitudinal x-section
A= endothelial cell
intima
B = PMN in vessel
C = basal lamina
underlying
endothelium
D = arteriolar
adventitia
E = smooth muscle
cell in media (b/c
this section is
longitudinal, the normally "fusiform, spindle-
shaped" SM cell appears round BUT STILL SHOULD ID THIS EASILY given it's LOCATION b/w ADVENTITIA + INTIMA (e.g. thus = media)
1
DO GEL READINGS QUICKLY if given a gel and asked for the complementary sequence look at
the TOP (which is negative side + therefore the end part of the given gene but we want
complementary so this will be start of that) + then just switch to complementary NT (eg AT)
only do for as much as needed to find answer in choices
immediately look at the last NT in sequence = G
Complementary will start with opposite of this = C so know strand starts C, T (vs. G, A)

MISSENSE mutation = MC MUTATION TYPE

Large segment deletion alpha thalassemia

2
BIOCHEM
Chronic arthritis, black urine Alkaptonuria
- Tyrosine
Liver and kidney dz 2/2 AA issue Tyrosinosis
Albinism Tyrosine def. melanin
Pale hair + r/o melanoma/skin ca
Pale hair + skin, MR, musty smell Phenylketonuria (AR)
Phenyalaninetyrisone deficient (phenyl enzyme or TB4
coenzyme)
Branched AAs Isoleucine
Leucine
Valine
Maple syrup urine dz CNS, MR, death, sugar-smell diaper)
*"I Love Vermont maple syrup"
MR, osteoporosis, marfinoid-habitus, lens subluxation Homocysteinuria
methionine/cysteine (cysteine becomes essential AA)
What RBC changes would you expect in a female who presents with an Inherited HEMOLYTIC anemia = 1. G6PD deficiency or 2. PK deficiency
inherited hemolytic anemia If woman, unless information given to suggest x-linked (and then
receiving 2 bad xs), most likely pyruvate kinase since this is not sex-
linked (AR)
NO Heinz (these are in G6PD RBC denaturation)
RIGHT SHIFT in oxygenation curve if PK, then glycolytic
intermediates back up alternate pathway includes 2,3 BPG
affinity for O2 (more offloading, LESS pickup - (REMEMBER,
fetal Hgb, HbF has 2,3BPG to allow for affinity/more pickup
from mom)
Heritability familial hypercholesterolemia AD

MOLECULAR + CELL BIO

RER secretory/exported proteins protein folding here
N-linked oligosacch addition
Nissl bodies in neurons ChAT enzyme that makes Ach; peptide NTs
GI goblet cells (mucous secretion), plasma cells (Ab-secretion)
Chaperones Class of specialized proteins that function to assist proper folding newly
synthesized proteins (properGolgiplasma mem etc.)
If they are dysfunctional + poor folding protein is polyubiquinated
lysosome for degredation
Will detect protein IN RER BUT WON'T find receptor (the protein) on
membrane (e.g. all is good until RER)
Ex calnexin, calreticulin
SER STEROID synth
DETOX rx, poison
hepatocytes (detox) + adrenal ctx (produces steroid hormones)

Golgi Proteins/lipids ERplasma membrane + vesicles

Modifies N-oligos on nitrogen of asparagine
Adds O-oligos on serine + threonine
Add MANNOSE-6-phos for traffic to lysosomes
o FYI : I-CELL DISEASE don't tag with mannose secrete
enzymes OUTSIDE cell instead of lysosome
Coarse face, clouded corneas, restricted jts,
plasma lysosomal enzymes
Fatal in chldhood
COPI retrograde, GolgiER

3
COPII anterograde, RERcis-Golgi
Endosome outside or Golgi lysosome or Golgi
Clathrin Trans-Golgi lysosomes,
Plasma membrane endosomes
R-mediated endocytosis (forms coat)
Peroxisome membrane-enclosed organelle for catabolism very LCFAs + AAs
Proteins destined for peroxisome incorporation synthesized on free
polysomes (ribosomes?)
Proteosome = degradation damaged/unnecessary proteins tagged by UBIQUITIN
Microtubule general action, processes - Cilia (details below), flagella
- Mitotic spindle
- Axonal trafficking
- Centrioles
*arranged with neg ( - ) end near centrosome (MTOC) + pos (+) radiates OUT
Microtubules - dynein vs. kinesin - Alpha + B-tubulin dimers, each with 2 GTP
- DYNEIN = RETROGRADE (+ -) e.g. toward NUCLEUS = NEGATIVE
(hannahs home-made mnemonics "I'm DYNING IN tonight"
(coming to the home/nucleus)
**CLINICAL CORRELATE herpes, polio, rabies viruses + tetanus toxin
are all exogenous substances that affect neuron cell bodies via
RETROGRADE axonal transport
(Im "DYing over here", regressing retrograde")

- KINESIN = ANTEROGRADE ( - +) e.g. away from nucleus

Tubulin Monomeric unites that comprise MT (necessary for movement cargo within cell)
Disease caused by defect in microtubule polymerization and Chediak-Hagashi MT polmerization defect fusion phagosomes+lysosomes
fusion of phagosome with lysosome Recurrent pyogenic infection
Partial albino
Peripheral neuropathy
Cilia structure 9+2 MT arrangement
Axonal dynein-ATPase links peripheral 9 dblts cilium bending
Disease caused by immotile cilia (and cause of immotility) KARTAGENERS immotile cilia d/t dynein arm defect
Male/female infertility
Bronchiectasis
Recurrent sinusitis
Situs inversus
Retrograde axonal transport dysf
Drugs acting on microtubules to treat fungus? To treat Mebendazole/thiabendazole anti-helminth
worms? To treat cancer (2)? To treat gout? Griseofulvin anti-fungal
Vincristine, Vinblastine anti-CA
Paclitaxel anti-breast CA
Colchicine anti-gout
Actin/Myosin general actions - *Microvilli
- Muscle ctx
- Cytokinesis
- Adherens junctions
Location where processing "goes wrong" in cystic fibrosis CFTR protein is misfolded in endoplasmic reticulum
- d/t F508 mutation (deletion phenylalanine) interference folding +
post-translational processing of oligosaccharide side chiains
- degraded by proteosome instead of membrane translocation
DNA ligase Catalyzes formation phosphodiester bond b/w 3' OH of DNA fragment with
adjacent DNA 5'-monophosphate grp

4
DNA Polymerase I Read 3' 5' (e.g. start at OH grp and read toward phos grp)
Synth 5'3' (adding new NT's phospho grp on to the free OH grp of growing strand
"hydroxyl attack" + energy from new NTs phos grp)
Both polymerization NTs and processing/repair mechs
Polymerase III Prokaryote only
Part of multiprotein complex, major replicating enzyme e. coli
Topoisomerase and Abx - swivel points in DNA to relieve strain at replication (cut+reseal DNA)
Quinolones interfere here
Cytosine deamination = URACIL if intact DNA repair mechanisms, these will be repaired (mismatch
repair genes will eliminate via base excision)
Dolichol Substrate for forming branched "carbohydrate trees" that are transferred to
proteins in synthesis glycoproteins (mostly protein w/ some attached sugars)
- on RER
- goes to golgi, then either plasma membrane/lysosome/secreted protein
"scientist wants to characterize the carbohydrate chains that will be transferred to
protein component of albumin. Which molecule functions for synthesis of these
chains?
*N-linked carbohydrate chains that will be transferred to protein component of
albumin are assembled in RER + attached to colichol phosphate

transferred to nitrogen of asparagine to form glycoproeins

- secreted = albumin
- retained in membrane = insulin-R
- targeted to lysosome = hexosaminidase A (tay-sachs)
Arachidonic acid Precursor of:
- PGs
- Thromboxanes
- Leukotrienes
FA in phospholipid membrane released by phospholipase A2
Ceramide Parent sphingolipid from which sphingomyelin, cerebrosides, gangliosides are
derived (think LYSOSOMAL STORAGE DISORDERS e.g. niemann-pick genetic
deficiencies of lysosomal enzymes that should digest these spingolipids cause the
diseases)
Dermatan sulfate GAG (glycosaminoglycan)
-precursor of proteoglycan (carbs w/ small proteins remember if protein>>carb
component = glycoprotein)
- part of ECM
Types: chondroitin sulfate, hyaluronic acid
Remember *dermatan + heparan sulfates are substrates to enzymes deficient in
HURLER (Worse, corneal cloud) + HUNTER dz
Tetracycline Binds ribosomal 30s subunit (prokaryotic small subunit euk = 40s)
prevents aminoacyl-tRNA attachment
Aminoglycoside Streptomycin, gentamycin, tobramycin, amikacin

Inhibits eIFs = elongating initiation factors that help assemble 30s ribosomal
subunit with initiatior tRNA

5
Ribosome formation, translation 30+50s = 70s prok
40+60=80s euyk

ATP activates tRNA (A=activatation)

GTP = initiation, translocation, holding on to tRNA (G=gripping, going places)

A site incoming aminoacyl-tRNA

P growing polypeptide chain
E = empty tRNA AA has been transferred to growing molecule on P site (exit)

Ribosome advances 3 NTs toward 3' end mRNA (e.g. toward end whose last NT
has free OH)
- This moves peptidyl RNA to P site = translocation
Chloramphenicol 2 MOAs at 50S ribosome
1. Inihibits 50S peptidyltransferase (this is the "top part" ribosome complex
2. Blocks peptide bond formation (so does clinda)
RIBOZYME RNA molecule that has catalyst (E.g. enzymatic "yme") activity
Ribosomal rRNA catalyzes peptide bond formation, transfers growing
polypeptide to AA in A site (which then moves to P site when ribosome moves 3NTs
forward)
Hammerhead Ribozyme Catalyzes sequence-specific cleavage RNA PDE bonds d/t 2 structure they form
(looks like head of hammer)
- possible use as treatment of "activating" mutated genes (e.g. SOD1 in ALS)
synthetic hammerhead RNA w/ complementary sequence to mutant SOD1 mRNA
could potentially bind specifically to mutant + destroy via catalyzing PDE bond
cleavage
"removes mRNA without direct inhibition of translation initiation" it's a
destruction rather than inhibition
Macrolides Erythromycin, azithromycin, clarithro static (Vs. cidal)

50S inhibitor blocks translocation this uses GTP normally

*(CHLORAMPHENICOL is also acting at 50S but blocking PEPTIDYLtransferase)

Clindamycin Same as second MOA chloramphenicol block peptide bond formation at 50S
ribosome
"Buy AT 30, CCELL (sell) at 50" 30S
Aminoglycosides (Strepto, genta, tobra) bacteriocidal
Tetracycline bacteriostatic

Mutation in early post-translational modification collagen
DNA methylation associated dz
50S
Chloramphenicol, Clindamycin static
Erythromycin (macrolide) static
Lincomycin static
Linezolid (variable static vs. cidal)
**Linezolid is for VREs
Ehler-Danlos skin + msk abnormalities
Fragile X
This in addition to TRI-NT repeat EXPANSION

CGG triNT repeat in FMRI gene r/o CHROMOSOMAL BREAK

nd st
- 2 MCC MR (1 = Downs)
- MACROCHORDISM (big testes), long face, LARGE + everted ears, autism,
MVP* (Fragile X = Xtra larges teses/jaws/ears)

6
Thick gums, large tongue, hip dislocation, clubbing feet,
relative immobility extremities and abnormal inclusions in
fibroblasts
Incorrect splicing introns associated with what hematologic
disorder
Hematologic dz caused by missense pt mutation
Transition vs. transversion pt mutation
Tautomerism switch point mutation
Significance of cytosine deamination
NT base with ketone
NT base with methyl grp
Alkylating agents
I-CELL dz
Def. N-acetylglucosamine-1-phosptransferase = defect in addition mannose-6-
phosphate moiety to lysosomal enzymes released to extracellar space so
culture medium will contain lysosomal enzyme activity
- Coarse facies, skeletal abnll, psychomotor retardation
- Type 1 complete def., death in childhood
- Type 3 partial deficiency = milder dz (pseudo-Hurler) survives to adulthood
B-THALASSEMIA
- B-globin gene (chr 11, HBB gene) incorrectly spliced to give B- or Bo
(small function)
HbS Sickle cell
Change A-->T at position 6 allows glutaminevaline
HbC = modified version this error (glutaminelysine)
- less serious and Asx if HbC/A but heterozygous HbS/C can act like HbSS
and homozygote HbCC gives hemolytic anemia
Transition is substitution within same "class" purinepurine / pyrpyr (same
ring "type")
Transversion = switch b/w purine/pyr (A-T T-A or C-G)
(remember Purine PURe As Gold = Glutamine, adenosine; pyrimidine CUT the
PY = cytosine, thymidine, uracil in proks)
Switch single vs. double bond via migration H+
Tautomers are isomers (structural isomers) of organic compounds that readily
interconvert by a chemical reaction called tautomerization.[1][2]This reaction
commonly results in the formal migration of a hydrogenatom or proton, accompanied
by a switch of a single bond and adjacentdouble bond. The concept of
tautomerizations is called tautomerism.Because of the rapid interconversion,
tautomers are generally considered to be the same chemical compound.
Tautomerism is a special case of structural isomerism and can play an important role
in non-canonical base pairing in DNA and especially RNA molecules.
CU this is the only deamination rxn that can be CORRECTED via uracil-DNA
glycosylase (this can be missed in mismatch repair HNPCC, endometrial CA)
*STEPS REPAIR:
1.Uracil-DNA glycosylase generates Abasic site = AP
2. DNA AP endonuclease sees newly formed Abasic site breaks PDE bond
3. DNA Polymerase sees break and creates nick + fills
4. DNA Ligase reforms seal with PDE bond
- ALSO CAN RECOGNIZE related deaminase rxn of METHYLATED cytosine
(methylated in regulation gene transcription epigenetics)
o 5methylcytosinethymine + ammonia (MC single NT
mutation) corrected via thymine-DNA glycosylase fixes
cystinethymine pt mutation in daughter cell
o **Remember, thymine is a methylated uracil so it makes
sense that CU would have methyl-CT
- all others NOT recognized
o Adeninehypoxanthine (this now prefers cytosine instead of
thymidine)
o Guaninexanthine (this now prefers thymidine instead of
cytosine)
*recall deamination = removal of amino grp from molecule
Guanine
Thymine
Cross-link guanine NTs in DNA damaging it enough to stop division
Cisplatin
Carboplatin
7
Base analog agents Incorrectly incorporate the analog into DNA but chemically different enough to not
make targeted protein, e.g. mismatch at base-pairing causes daughter DNA
mutated

BrdU find replicating cells for research

Methylating agents Transfer methyl grps to DNA NT bases (not used for cancer Rx since it doesn't lead
to cell death)
*MGMT = methylguanine methyltransferase repairs

EMS = ethyl methanesulfonate guanine alkylation that can induce high rates of
mutations used in genetic screens/assays to induce mutations to be studied
Antimetabolite 5-FU (fluorouracil) pyrimidine analog; "suicide inhibitor" irreversible inhibition
thymidylate synthase

Antipurine azathioprine (cleaved to 6-MP), thioguanine

Antifolate MTX (analogue that binds, inhibiting DHFR and formation THF), TMP,
pyrimethamine, pemetrexed
DNA intercalating agent Insert b/w 2 NT pairs DNA transcription/replication

Fluorescent dye Ethidium Bromide

DNA cross-linking agents
Cancer Rx Doxorubicin, Daunorubicin
Aflatoxin = Aspergillis
Thalidomide teratogen with strict use policy for last resort anti-inflammatory
(leprosy) + salvage chemo in MM (With dexamethosone)
Birth defect = PHOCOMELIA (horrible limb deformities as well as other
body regions)
Form covalent bond b/w DNA NT bases can't replicate/transcribe

Platinum
Free radicals Highly active in presence of unpaired electrons
- Age-related cell damage
Superoxide
H2O2
Hydroxyl radicals
Ionizing mutagens + UV UV = wavelenth/energy vs. normal length covalent adjacent thymine bond
formed THYMINE DIMER (r/o skin ca)

Ionizing radiation radioactive materials with high energy that REMOVE electron
from molecule/atom damage/death
Mutagens requiring repair via base excision Xrays
O2 radicals
Alkylating agents
Spontaneous rxns
uracil abasic sites created (AP sites) or single strand break (MCC = CU
deamination)

DNA glycosylase + AP endonuclease remove/repaire, polymerase+ligase fill in

Errors of replication A-G mismatch
T-C mismatch
Insertion
Deletion

Mismatch repair (hMSH/hMLH)

8
Recombinational repair
N-terminal hydrophobic signal sequence added on during
synthesis via cytoplasmic ribosomes
Lysosomes
Intermediate filament stains vimentin Connective tissue
Intermediate filament stains desmin Muscle
Intermediate filament stains cytokeratin Epithelial cells
Intermediate filament stains GFAP neuroGLIAL cells astrocytoma, ependymal cells
Intermediate filament stains neurofilaments Neurons
Drugs that act on microtubules
Dynein arm defects
Partial albinism, peripheral neuropathy and recurrent
pyogenic infections 2/2 molecular bio issue
Kinesin vs. Dynein
Make-up of microvilli
Actin, myosin, MT roles in replication
Plasma membrane composition leading to decreased fluidity
and higher melting temp
RER activity + what cells have more
SER activity + what cells
One damaged strand has some replication use as template
Nonhmologous end-joining (ALWAYS MUTAGENIC) DNA ligase complexes join
separate ends dbl helix
Sequence = "signal recognition particle" (SNP) attaches growing peptide +
ribosomal complex to RER opens up channel allowing peptide to thread into ER
lumen
Will be on any protein destined to be secreted / membrane-bound / lysosomal
If absent protein would be UNABLE TO enter RER in first place (pre-folding
error)
Contain enzymes (made in RER) that degrade sugars (glycosidases) + proteins
(proteases)
*note connects cytoplasmic bodies to membrane dense plaques in actin filament
structure of smooth muscle; cardiac + skeletal myopathies associated w/
mutations in this protein
**REMEMBER GFAP only marks astrocytomas, for prognosis use Ki-67
Mebendazole/thiabendazole anti-helminth
Griseofulvin anti-fungal
Vincristine, Vinblastine anti-CA
Paclitaxel anti-breast CA
Colchicine anti-gout
KARTAGENERS immotile cilia d/t dynein arm defect
Male/female infertility
Bronchiectasis
Recurrent sinusitis
Situs inversus
Chediak-Hagashi MT polmerization defect fusion
phagosomes+lysosomes
Recurrent pyogenic inection
Partial albino
Peripheral neuropathy
DYNEIN = RETROGRADE (+ -) e.g. toward nucleus
KINESIN = ANTEROGRADE ( - +) e.g. away from nucleus
actin/myosin NOT microtubules
Actin/myosin = cytokinesis
Microtubules = mitotic spindle, centrioles
MORE cholesteroal and/or MORE long saturated FAs
- secretory/exported proteins
- N-linked oligosacch addition
- Nissl bodies in neurons ChAT enzyme that makes Ach; peptide NTs
- GI goblet cells (mucous secretion), plasma cells (Ab-secretion)
STEROID synth
DETOX rx, poison
hepatocytes (detox) + adrenal ctx (produces steroid hormones)
9
Mitosis order Interphase
Prophase
Metaphase
Anaphase
Telophase

"PMAT" or "People Meet And Talk"

Hand action mnemonic

Sign and significance of tripolar mitoses
2 drugs that act on Na/K ATPase channel directly (not neuro)
Na/K pump activation
Collagen types I IV
Disease a/w DEFECT in Type 1 collagen
Prophase = fingers linked together in the middle
Metaphase = MIDDLE (flat hands)
Anaphase = pulled APART (hands apart)
Telophase = TWO (close fingers to two fists)
= 3 clusters of chromosomes seen on telophase
Signifies malignancy in tumor
Ouabain binds K+ site
Digoxin/digitoxin (glycosides) direct inhibit Na/K = indirect inhib Na/Ca (true
target) [Ca2+]in = contract
Phosphorylated = ACTIVE
ATPADP (donates phos)
"Be (So Totally) Cool, Read Books
I = Bone, Skin, tendon
Type ONE = BONE
II = cartilage (with hyaline), vitreous body + nucleus pulposus
Type TWO = carTWOlage
III = Reticulin = skin, vessels, uterus, fetal tissue, granulation tissue
Type III = ThreE D defective in Ehlers-Danlos
IV = Basement membrane (Easy, think goodpastures)
"Four = Under the Floor"
Osteogenesis imperfecta ("BRITTLE BONE") COL1A1/2
The one that looks like child abuse
Multiple fx w/ minimal trauma
BLUE SCLERA (translucent CT over choroid)
Hearing loss (ABNL MIDDLE EAR BONE)
DENTAL lack dentin

*remember
I = Bone, Skin, tendon
Type ONE = BONE

10
Disease a/w DEFECT in Type 3 collagen Ehlers-Danlos COL3A1 collagen + lysine hydroxylase gene mutations
Hyperextensible skin
Easy BRUISING/Bleeds
Hypermobile jts
**6 types w/ varying inheritance/severity (AD or AR)
TYPE 4 (rare) = MENKE's dz (x-linked depigmented, lusterless KINKY hair
with many facial/ocular/vascular/cerebral manigestations, copper
transport defect and activity copper-depndent enzymes LYSYL
OXIDASE REMEMBER, THIS IS CU-DEPENDENT ENZYME that crosslinks
pre-collagein in ECM to form mature collagen)
+/- associated with:
Joint dislocation
BERRY ANEURYSM
Organ rupture
*remember
III = Reticulin = skin, vessels, uterus, fetal tissue, granulation tissue
Type III = ThreE D defective in Ehlers-Danlos
Disease a/w DEFECT in Type 4 collagen Alport Syndrome (goodpasture = autoimmune not defect)
hereditary GN
ESRD
HEARING LOSS
+/- ocular disturbances
MC type = X-LINKED RECESSIVE (BOYS)

*remember
IV = Basement membrane (Easy, think goodpastures)
Collagen 4 steps within fibroblasts + location 1. Synthesis (RER)
o Translate alpha chains = PRE-PRO-collagen
o Gly-X-Y
X/Y = PROLINE, hydroxyproline/LYSINE
2. Hydroxylation (ER)
o Of Proline + lysine residues VITAMIN C CRITICAL
3. Glycosylation (ER)
o Of Pro-alpha-chain hydroxylysine residues + formation PROcollagen via
H + DISULFIDE BONDS
o TRIPLE HELIX of 3 alpha chains
4. Exocytosis
o PROCOLLAGEN extracell
Collagen 2 steps outside fibroblasts 5. Proteolytic processing
- CLEAVE terminal region = procollagenTROPOcollagen (insoluble)
6. Cross-link
- reinforce tropocollagen via covalent LYSINE-HYDROZYLYSINE CROSS-LINKSb
(LYSIL OXIDASE) FIBRILS
Implicated genetic defect in osteogenesis imperfecta Type I collagen disorder
ColA1, ColA2 unstable collagen triple helix not as strong (phenotypic outcome
depends on unique changes in genes)
2 MC AAs in collagen Glycine
Proline
Gly-X-Y where X = proline (or lysin/glycine), Y = hydroxyproline)
Cartilage with PAS stain Type III Reticulin (skin, vessels, uterus, fetal tissue, granulation tissue)
Lysyl oxidase Involved in forming collagen fibrils from pro-collagen triple helices that have been
secreted into extracellular space
*Copper-dependent
Cross-linkage via covalently binding LYSINEHYDROXYLISINE Fibrils

11

Cofactor requirement in early collagen synth
Elastin
Disease MC a/w elastin defect
Elastase and associated disease
Ddx uric acid + gout primary reasons
Ddx uric acid + gout secondary reasons
nd
VITAMIN C 2 step (HYDROXYLATION) within fibroblast in ER
Without = SCURVY
Weakened vessels = ulcerated gums, tissue hemorrhage, anemia, wound
healing, loose teeth, bone formation
Stretchy protein in lungs, large arteries, elastic ligaments, vocal cords, ligamenta
flava (connect vertebrae for relaxed + stretched conformations)
PROLINE, GLYCINE NONglycosylated forms
Tropoelastin w/ fibrillin scaffold
Marfans fibrillin gene
**FIBRILLIN = large ECM proteins a/w elastic + non-elastic microfibrils
Breaks down elastase normally balance break down/build up but in alpha-1-
antitrypsin excess elastin = EMPHYSEMA (panacinar) + CIRRHOSIS/liver failure
(#1 cause liver transplant in newborns!
Lesch-Nyan
Alcoholism
G6PD
Hereditary fructose intolerance
Galactose-1-P uridyle transferase def. (severe galactosemia)
**all disoders with increased accumulation of phosphorylated sugars =
degradation products (e.g. AMP uric acid)
OVER-PRODUCTION
Leukemia
Myeloproliferative syndromes (MPDs)
MM
Hemolysis
Neoplasia
Psoriasis
Alcoholism

UNDER-PRODUCTION
Renal failure
ASA
Diuretics
Alcohol (all 3 categories)
Direction DNA synthesis 5'3'
Direction RNA synthesis 5'3'
Direction DNA/RNA read 5'3' (e.g. mRNA is read 5' 3')
Protein synth NC
Actinomycin D Binds DNA, preventing RNA polymerase from moving along template
Rifampin Binds B-subunit RNA polymerase, inhibits initiation RNA synth
Interstitial deleting Large DNA fragment deleted on single chr pairing 2 genes not normally in
sequence with one another (e.g. could bring activation one gene from another)
Fusion oncogene
Chromosomal inversion Large large segment becomes reversed w/i same chromsome rearrangement
post-breakage chr = fusion oncogene
Ouabain Binds K+ on Na/K pump, inhibiting Na/K ATPase
Digoxin/digitoxin Cardiac glycosides
Direct bind/inhibit Na/K ATPase indirectly inhibiting Na/Ca exchange = Ca in
cell = contractility
Normal amount of an enzyme present yet no enzymatic NONSENSE mutation AA change generating 1 of 3 stop codons
activity where is mutation? mRNA is transcribed correctly but during protein translation, would stop early
(truncated, ineffective)
Three stop codons UGA UAG UAA
(U Go Away, U Are Gone, U Are Away)

12
Test for carrier genetic disease
Steps in testing Lyme
Area where splice acceptor mutation occurs
snRNP
Location cleavage propetides collagen
Cofactor required by phenylalanine hydroxylase
What "substance" crosses plasma membrane fastest?
E-cadherin
Occludin
Desmoglein
Sites of synthesis proteins destined for lysosomal
incorporation
Bullous pemphigous vs. pemphigus vulgaris
Action of alpha-1-adrenergic agonist (e.g. phenylephrine) on
vessels vs. muscarinic
Muscle band changes during ctx A, I, H
PCR
Amplify sequence of question and compare to normal
ELISA first screening sensitive, rapid (can have false+)
Follow-up with more specific WESTERN BLOT (protein)
3' end eukaryotic intron (invariant AG just before end intron) HIGHLY
CONSERVED
5' end intron = GT (GU in RNA) necessary splice donor site
Spliceosome
removes introns recognizing GT at 5' + AG at 3' end = splice sites)
mutation here greatly alters protein (B THALASSEMIA = SPLICING DEFECT
chr11, HBB gene additional, contiguous length non-coding mRNA or
discontinuous fragment = SNP SINGLE NT POLYMORPHISM)
Extracellular first step; therefore is always "pro" type of collagen within cell
Tetrahydrobiopterin
*Defect in either PKU (MR, hypopigmentation)
CO2, followed by O2 then nitrogen, inhaled anesthetics etc.
diffusion is as rapid for these gases as it is for them in water
CO2 has higher solubility vs. water
Allows formation of junctional complexes (critical for formation and maintenance)
via homotypic interaction b/w each other (cadherins) that initiates formation zona
adherens (including signaling paths) which are then activated to initiate formation
zona occludens + desmosomes
Transmembrane cadherin specific to zona occludens tight junctions
Transmembrane cadherin specific to desmosomes
e.g. forms intercellular linkages at desmosomes which connect epithelial cells
PEMPHIGOUS VULGARIS anti-desmoglein Abs
o Irregularly shaped erosions in GINGIVAL, BUCCAL, palatine
mucosae
o POSITIVE Nikolsky test apply pressure + epidermis appears
to separate from underlying dermis
o Bx: acantholysis w subsequent loss of cohesion
RER
Bullous =autoimmune IgG rxn vs. HEMIDESMOSOMES (collagen type XVII aspect)
Pemphigous = DESMOGLEIN, tight junctions specific to epithelial cells, blisters,
positive nikolsky, oral ulcers
Alpha-1 agonists stimulate R on SM [Ca2+]in (IP3, DAG qiss Gq)
contraction (constrict vessel)
Muscarinic can induce NO release (aka EDRF endo relaxing factor); produced
from arginine by endothelial cells
A = NO CHANGE
I = shorten
H = shorten
(think A is the best, so no need to improve, no need to )
A-spans width myosin thick filaments
(INCLUDING overlap actin thin)
length set by length of mysoin (thus
no @ctx)
H = thick myosin WITHOUT overlap
actin
I = actin filaments ONLY
Z line where actin filaments attach
13
MUST KNOW THIS too easy to not MUST KNOW THIS too easy to not have on tip o
have on tip o tongue tongue

Calculating changing osmolarity Mass solutes in cell dont change (while fluid volume
Ex: cell with osmolality of does)
300mOsm/kg is placed in salt solution Mass intracellular solute before = C1V1
and grows to be 1.5x original size. Mass intracellular solute after = C2V2
What is osmolality soln? C1V1 = C2V2
300mosm(1) x(1.5) X = 200

Diseases caused by DNA mutation/repair defects

KEY NER = NT excision repair, AR = recessive, AD = dominant
Dz Defect Inheritence Manifestations Tx
Xeroderma pigmentosum NER AR r/o all skin CA (1,000x) 1. retinoids - CA but
incidence Japan irreversible calcification
tendons/ligaments
- acitretin treats keratoses,
also used in psoriasis
2. 5-FU (pyramidine analog
antimetabolite)
Cocakyn's syndrome NER AR Bird-facies (thin nose, small head, large ears) No cure supportive
Retinopathy, dwarf with long limbs,
photosensitive *CS2 worse than 1
Hyperpigment, erythema, teleangiectasias
Premature aging
Trichothiodystrophy NER AR Sulfur Rare, no cure
Brittle hair/nails
Fish skin scaly
Physical/mental retardation
Fanconi's Anemia ROS AR BM fail w DNA repair defect Tx symptoms
11 genes - petechiase, bruise, pallor, caf-au-lait (anemia/leukemia/CAs)
DNA repair - infection, fatigue
- aplastic anemia (pancytopenia), leukemia,
Cycle ctrl solid tumors (CA liver, neck, esophagus,
vulvar)
Bloom Helicase AR growth w/ r/o malignancy
Butterfly facial telangiectatic erythema
Chr. Instab. -resp/GI infection
Werner's Helicase AR Aging, thin, tight, scleroderma-like skin First 10 yrs of life normal
(WS gene) muscle, wrinkle, hyperkeratosis death 40yo
Cataracts, osteoporosis, arteriosclerosis, CA,
DM No tx
Japan, M=F

14
ATAXIA-TELANGIECTASIA Chromos + AR Heterogenous, but marked by Treat Sx
chromatid chr 7 + 14, neurodegeneration (ataxia) + telangiectasia Death teens
breaks w ATM gene (2/2 dilation vessels)
rearrangmt **(= TCR + Ig - sino-pulm infections
regulation r/o CA, sensitive to xrays/radiation
chr)**
HNPCC/ Mismatch AD Change in # of repeats of germline alleles C'scope q2yr at 25yo, q1yr
LYNCH SYNDROME repair MSH2, accumulation mutations @40yo (colectomy usual at this
Microsat. MLH1, 80% r/o CRC pt)
Instability (PMS2), Ras Females have 30-50% r/o endometrial
genes **L colon>R colon unusual**
BREAST CA p53 AD 60-80% r/o serous adenoCAs CA tx same as regular breast CA
DNA repair, BRCA1 but can do ppx mastectomy
cycle BRCA 2 = ovarian, prostate, pancreatic

GENETICS
Blotting which for what SNoW DRoP
S = DNA
N = RNA
W = Protein

Southwest = DNA-binding proteins (TF factors)

This makes sense DNA = South, TF=Protein = West
Use labeled oligoNT probes
Blot that allows determination of whether Northern blot
absence of protein is due to failure gene Isolate RNA from PMNs gel, blot, 32-P-DNA probe for specific gene
transcribed vs. post-transcriptional defect
Technique used to separate false positive HIV- Western blot
ELISA from true positives
Uses DNA-DNA hybridization Southern blot
Indirect geenetic testing within families, relatedness of individuals,
determination epidemiologic relatedness of bacterial biotypes, e.g. strains
S aureus producing TSS
Blot that gives semi-quantitave result for level of Northern blot
gene expression in tissue
15
Microarray use (for usmle at least)
Test used to test for antibodies
Uses of FISH
Steps in production recombinant DNA (for
cloning)
Conditional vs. constitutional transgenic mice
RNAi
When in mitosis do you stain for karyotyping?
Microsatellite instability
Lab technique that is best at detecting whether
disease is heritable form (E.g. gene deletion) or
sproadic
Method of coupling Abs to fluorescent markers
to determine cell surface markers of whole cells,
e.g. CD34+ stem cells
Term - Codominance
Term variable expression
Term incomplete penetrance
SNP detection (single NT polymorphisms) to study dz/tx
Genotyping
Forensics
Predisposition to dz
Cancer mutations
Genetic linkage analysis
*detecting relevant amt complementary nucleic acid sequences to dna/rna
probes
ELISA
Two methods:
1. Pts blood + test antigen (coupled to enzyme probe) does pts
immune system recognize?
2. Pts blood + test antibody (coupled) is antigen present?
Most sensitive/specific for HIV 100% each
Microdeletions at molecular level (when deletion too small to see on
karyotype
Fluorescent gene is present
None = gene has been DELETED
Isolate eukaryotic mRNA (post-RNA processing)
Expose to reverse transcriptase cDNA
Insert cDNA into bacterial plasmid containing antibiotic resistance genes
surviving bacteria on Ab medium produce cDNA library
Conditional = targeted insertion/deletion gene via homologous
recombination
Constitutive = random insertion gene into mouse genome
dsDNA made to separate + degrade target mRNA
Synthesized to complementary mRNA
Metaphase
Characteristic with loss-of-function in mismatch repair genes (hMLH, hMSH
HNPCC, endometrial CA, ovarian CA, gastric CA)
Areas of diNT repeats a/w "slippage" @replication that s number of
repeats on new strand (=instability)
o Mismatch repair genes would normally fix
*Normal microsatellites can be 2-4bp totaling <150bp total (repeats =
instability)
PCR can see size DNA of amplified band
If INHERITED ALL CHROMOSOMES in body will show shorter allele WHEREAS
SPORADIC will ONLY have abnormal/short allele IN TUMOR tissue/cell-types
FACS
Neither of the 2 alleles are dominant
Blood groups (A, B, AB) O is "no allele"
Nature + severity phenotype vary 1 personanother
2 pts w/ NEUROFIBROMATOSIS may have varying severity
Not all individuals with mutant genotype show mutant phenotype
16
Term pleiotropy
Term - imprinting
Term loss of heterogeneity
Term Dominant negative mutation
Term linkage disequilibrium
Term - Mosaicism
Term Locus heterogeneity
Term heteroplasmy
Term uniparental disomy
1 gene > 1 effect on person's phenotype (sort of opposite locus heterogeneity)
PKU causes many seemingly unrelated symptoms (MR hair/skin s)
OSTEOGENESIS IMPERFECTA (excess atypical fx, scoliosis, basilar skull
deformities, blue sclerae, opalescent teeth, skin laxity)
Diff in phenotype depends on whether mutation is of maternal vs. paternal
origin
PRADER-WILLI Dad "happy puppet"
ANGELMAN'S Mom hyperphagia + obesity
Chr15*
Patient inherits/develops mutation in tumor suppressor gene then the
COMPLEMENTARY allele must be deleted/mutated BEFORE CA develops
RETINOBLASTOMA (Rb p100)
Exerts DOMINANT EFFECT heterozygote has non-functional altered protein
that prevents normal gene product from functioning
MUTATION of TF in its ALLOSTERIC SITE nonfunctioning mutant can still
bind DNA thereby PREVENTING wild-type TF from bnding
Tendency for certain alleles to occur together more often than expected by
chance
Measured in population NOT family + varies between different pops
Occurs when cells in body have different genetic makeup
- Can be germ-line mosaic can produce disease not carried in parent's
somatic cells
LYONIZATION- random X inactivation in females
DOWN'S trimsomy w/ mosaicism 47, +21 /46 -2-3% Down's, less severe
phenotype (IQ etc) has half normal cells, half not
NON-disjunction chr21 occurs DURING MITOSIS NOT MEIOSIS in an
early cell division)
Mutations at different loci produce same phenotype (Sort of opposite
pleiotropy)
*MARFAN'S, MEN 2A/B + HOMOCYSTEINURIA all cause MARFINOID HABITUS
*ALBINISM (+ acular type e.g. color-blindnessb)
*OSTEOGENESIS IMPERFECTA (type 1 procollagen chr7 OR chr 17 BOTH lead
to imperfect formation trimeric protien)
Presence both normal + mutated mtDNA = variable expression in
mitochondrial inherited dz
LEBER'S HEREDITARY OPTIC NEUROPATHY
degeneration retinal ganglion cells + axon leading to
acute loss vision
Offspring receives 2 copies chr from 1 parent and no copies from other
17
NONDISJUNCTION meiosis 1 vs. 2
Reciprocal vs. Robertsonian translocation
3 DIFFERENT types Down's inheritance
Pedigree with horizontal transmission
Pedigree with vertical transmission
Pedigree x-linked recessive
Pedigree x-linked dominant
Example x-linked dominant
Heteroplasmy
NONDISJUNCTION = failure of paired chromosomes to separate + go to diff daughter
cells leading to one daughter cell getting extra chromosome (n+1) while the other is
one chr "short" (n-1)
MEIOSIS I - if NONDISJUNCTION HERE child will get 3 different copies of gene (2
from 1 parent + 1 from other parent) b/c homologues carry SIMILAR but NOT
IDENTICAL info
MEIOSIS II sister chromaatids (2 identical copies SAME chromosome) should separate
if NONDISJUNCTION HERE 2 copies SAME EXACT chrosome passed to progeny
(e.g. 1 allele x2 from 1 parent and one from other)
SUM if mom has alleles A+B, dad has C+D if kid gets A, B, C = meiosis I A, A, C =
meiosis II
RFLP (restriction fragment length polymorphism) can detect region near centrosome of
a chromosome (E.g. chr21) surrounding region exhibits crossover suppression
genetic exchange canNOT occur in this area and so probe = reliable marker individual
chromosome
Reciprocal: true exchange DNA chrchr (fragments b/w chromosomes) FUSION
GENE or CHANGE EXPRESSION existing gene
BCR-ABL 9;22 CML
Robertsonian: large fragment 1 chr another WITHOUT a "return" of DNA (e.g. non-
recipricol)
ACROCENTRIC CENTROMERES (
o 13, 14, 15, 21, 22
Minority DOWN's has 2114 robertsonian (MCC Downs = trisomy)
1. Trisomy 21 (47, +21) - MCC
2. Trisomy MOSAICISM 21 (47, + 21 / 46) 2-3%
a. 2 "populations" of cell types normal cell line (46 chrs) AND
nd
2 line w/ trisomy 21
i. Less extreme phenotype (e.g. IQ)
3. Robertsonian translocation (2114)
AR all effected are in same generation, e.g. unaffected parents but affected
kids
- 25% offspring 2 carrier parents affected, see in one generation only
(usually)
- Commonly more severe than AD disorders shows up in childhood
AD 50% offspring affects, across generations
- Often PLEIOTROPIC, presenting after puberty
- FH crucial to dx
M > F (female must be homozygous), but dad never passes on to his son (e.g.
NO malemale transmission)
- 50% sons to MOM CARRIER affected (heterozygoous mom)
-
*If DAD is affected ALL DAUGHTERS affected
*If MOM is affected Sons and daughters MAY be affected
HYPOPHOSPHATEMIC RICKETS (formerly = vitamin-D-resistant rickets)
- phosphate wasting PROXIMAL TUBULE
rickets-like presentation
Normal AND mutant MITOCHONDRIAL DNA (mtDNA)are expressed
18
Ex of mitochondrial inheritance + genetics
inheritance
Female who is heterozygous for X-linked
recessive gene can sometimes have mild
expression of disease phenotype - how?
Female expressing FULL phenoytype of x-linked
recessive disease
Hardy-weinberg
Given that 1 partner is heterozygous for an
autosomal recessive trait (pq) and the
frequency of dz (A), AND NO OTHER INFO, how
could you predict the chance that the partner
will have a diseased baby without knowing the
other partner's status?
*transmission via mom only all offspring (M/F) may have signs dz
**often d/t failure oxidative phosphorylateion
- Variable exprssion d/t heteroplasmy
MITOCHONDRIAL MYOPATHIES
- LEBERS HEREDITARY OPTIC NEUROPATHY acute loss of central vision
- MYOCLONIC EPILEPSY
- MITOCHONDRIAL ENCEPHALOPATHY
"RAGGED RED FIBERS" on microscopy
X inactivation is random event normally, female has enough "normal"
phenotype b/c on average, of cells will express normal allele HOWEVER,
extrae degrees of X-chr inactivation can lead to predominance one allele
can express gene
G6PD mild anemias
Hemophilia mild bleeding
Possible if concomittant TURNER'S SYNDROME (SHORT stature etc) since only
1X
WILL SEE ABNORMAL KARYOTYPE will see a missing sex chr
2 2
p + 2pq + q =1
p+q=1
generally, given disease freq
2
(p ) or allele freq (p)
if GIVEN disease freq, than
2
calculate mutant allele freq = p = p
Using, p, find normal allele freq = 1-p = q
Now can determine carrier freq = 2pq or if asked to predict FUTURE baby given
just one partner, using the calculated p+q AND BE SURE to account for various
possible outcomes as you would with ANY baby problem e.g. if asking about
baby carrier status to a heterozygote + normal person, than know it is 50% but
nd
if you DONT know status 2 partner, use allele freq population as frequency
that gene in partner (almost as though treating like variable penetrance) see
below problem
2
If frequency of dz = A,, then a = p
- allelic frequency = A this will also be EQUAL TO frequency egg
carrying the recessive allele (a, or pA)
- if 1 partner is KNOWN CARRIER, there is 50% of passing on recessive allele
- thus, chance that he will have a child with the disease = (0.5)( A), i.e.
(0.5p)
nd
with numbers: if 1% population has X and 1 partner is carrier, 2 partner
status unknown
0.01= p p = 0.1
2
19
Change in H-W equation if disease is X-linked
ASSUMPTION MADE IN H-W EQUATIONS
LINKAGE DISEQUILIBRIUM
Genetic drift vs. gene flow
Males hemizygous = 1 allele FREQUENCY OF ALLELE will be EXACTLY THE
2
SAME as the GENOTYPE e.g. q = q (incidence dz = incidence allele)
MALES: p + q = 1 is equation expressing allele freq AND gen. freq
2 2
FEMALES: p + q = 1 allele freq ONLY; for gen. freq, need p + 2pq + q =1
"The incidence of DMD in N. America is 1/3000. Based on this frequency, what
is the gene frequency of this trait?" 1/3000!
**ON EXAM, BE CAREFUL they will not say "THIS IS X-linked" so PAY
ATTENTION to the DISEASE BEING MENTIONED do not go right to equation
b/c it changes If x-linked
(x-linked = Boys Wish For Hannah's GOLD Hockey Skills bruton's
agammaglobulinemia, wiskot-aldrich, fabry's, hemophilia, G6PD, ocular
albimism, lesch-nyhan, duchennes(+beckers), hunters syndrome)
P=1
**DONT FORGET TO MULTIPLY BY 2 TO GET CARRIER FREQUENCY after
calculating q (carrier = 2pq and if p=1, carrier = 2q)
Preferential association of allele at one locus with another allele at nearby
locus more frequently than be chance alone
DRIFT gene frequency d/t FINATE population size would ONLY SEE in
small/closed communities
FLOW gene exchange b/w different populations
20
 WORKING THROUGH ALPHA-THAL genetics

27yo Asian-American male comes to ED with RUQ abdominal pain + nausea. Studies show mild, microcytic hypochromic anemia + target cells.
Has a ____ who died at birth from blood disease and uncle with HbH. Wife has completely normal blood. Chance that patient will have carrier
child. We know that BOTH parents must have one completely normal alpha/alpha allele and one completely abnormal - - / - - allele to have had
hydrops baby. Because patient is presenting with symptoms, can
assume he carries trait, e.g. 2 bad alleles out of 4 AND since he is living
must have one full normal + one full abnormal e.g. ( a a / - -)
will have 50%
chance
passing on (a
a) allele and
50% chance of
passing on bad
( - -) allele. Since
wife is clean, 50%
chance child
will have trait

*NOTE* the double mutant allele (a a ) is MC in asian population. Otherwise, more frequently have trait with (a - / a - ) or silent carrier (a - / a a )

**REMEMBER** 2 variations "alpha-thal trait" (a a / - -) OR (a - / a - ) 2 alleles

HbH = (a a / a - ), Hydrops = (a a / a a) 3 + 4 alleles
Silent carrier = ( a - / a a) 1 allele

Disorders by mutated gene/function (see separate "Chromosomal" table too)

ATM gene mutation ATAXIA TELANGIECTASIA
(as name implies) multiple dilated vessels + progressive ataxia
Gene kinase responsible for recognizing/correcting errors in duplicating
DNA during cell division
normal = repair ds DNA break
mutant = sensitivity ionizing radiation frequent chromosomal
abnormalities
incidence MALIGNANCIES ESPECIALLY lymphoreticular (these cells are
dividing most frequently) = HL, NHL, leukemias
Excision endonuclease XERODERMA PIGMENTOSUM
UV light sens freckles, skin CA, corneal ulcerations
Gene thymine dimer repair via nick PDE bond on strand w/ dimer on both
sides + removes
Defect dimers persist

21
Splice site mutation (5' UTR of ATP7B gene) WILSON'S
Copper accumulation (d/t absence ceruloplasmin) in liver, brain, cornea
- Asterixis
- BG degeneration producing parkinsonian sx
-Kayser-Fleisher rings corneal deposits
DOWN's 1. TRISOMY 21 (47, +21) - MCC
2. Trisomy MOSAICISM 21 (47, + 21 / 46) 2-3%
a. 2 "populations" of cell types normal cell line (46 chrs)
nd
AND 2 line w/ trisomy 21 nl, not
i. Less extreme phenotype (e.g. IQ)
NON-disjunction chr21 occurs DURING MITOSIS NOT
MEIOSIS in an early cell division)
3. ROBERTSONIAN TRANSLOCATION (2114)

DOWN'S trimsomy w/ mosaicism 47, +21 /46 -2-3% Down's,

Chromsomal disorders - specific chromosome locations

Disease Chrom- Gene Manifestations
Osome
CYSTIC FIBROSIS 7 CFTR Protein misfolded and improper oligosacch additions at endoplasmic
AR F508 reticulumproteasome (degredation) instead of plasma membrane
(phenylalanine delete) Pseudomas, S. aureus infections PNA, bronchitis/bronchiectasis
Pancreatic insuff, steatorrhea, VitA/D/E/K def
Male infertility
Biliary cirrhosis, meconium ileus
Dx NaCl on sweat test; PCR + ASO probes
Tx enzyme + vitamins etc
N-acetylcysteine (LOOSENs mucus plugs CLEAVES disulfide bond w/i
glycoproteins)
MEN 2A/2B 10 RET RTK that binds neutrophic BOTH 1.medullary thyroid CA 2. pheochromocytoma;
AD factors that signal cell to plus
grow+divide (gain of A=pituitary adenoma
function/activating) B=oral/facial ganlioneuromatosis (e,g, mucosal neuromas- LIPs) +marfinoid

**OTHER RET = hirschsprungs

PRADER-WILI 15q11 (deletion in area affected by Maternal deletion (With silent, methylated father allele) = AngelMans
VS. imprinting) (happy puppet)
ANGELMAN Paternal deletion (silent/methylated mom allele) = Prader-Willi (MR,
hyperphagia+obesity with initial poor feeding)
CRI-DU-CHAT 5q microdeletion High pitched monotonic cry
- Microcephaly, wide-set eyes, MR
- Epicanthial folds
- CARDIAC ABNORMALITIES, e.g. VSD

LI-FRAUMENI AD p53 r/o breast CA, colon CA, soft-tissue sarcoma, osteosarcoma, brain tumors,
Loss-of-function leukemia + adrenocortical CA
mutation/deletion tumor
suppress gene

22
MICROSATELLITE AD w/ hLMH1 + hMSH2 MC association = HNPCC but also in:
INSTABILITY (2+) variable mismatch repair genes - Endometrial CA
pene- - Ovarian CA
trance - Gastric CA

DIGEORGE 22q11 *thymus structural/functional defect; missing T-cell immunodeficiency

*hypoparathyroid = 2 hypercalcemia
*craniofacial abnormalities, palate
SICKLE CELL AD Glutaminevaline @position 6 in Beta-globin gene
WILMS TUMOR 11p13 Microdeletion Malignant urinary tract tumor
2/3 dx by 4yo
Surgical removal

NEUROFIBROMAT 17 NF1 tumor-suppressor gene 90% NF cases (vs. type 2)

OSIS AD Multiple neurofibromas
TYPE 1 Caf-au-lait
(VON Lisch nodules pigmented iris hamartomas
RECKLINGHAUSEN) r/o pheochromocytoma + mengingiomas

NEUROFIBROMAT 22 NF2 tumor suppressor gene BILATERAL acoustic neuromas (schwanomas is tip-off) otherwise,
OSIS AD the rest are both NF1/2:
TYPE 2 Neurofibromas
Caf-au-lait
r/o meningioma+pheo

MARFAN 15 FBN1 fibrillin 1 Marfinoid habitus tall, hyperextensible, pectus excavatum +

AD kyphoscoliosis
**FIBRILLIN = large ECM proteins Subluxation lens
a/w elastic + non-elastic Heart defects
microfibrils o Cystic Medial Necrosis of aorta
o Dissecting AA
o Valvular insufficiency Mitral regurg = holosystolic murmur
in apex
o MVP = midsystolic click)

VON HIPPEL- 3 VHL = tumor suppressor gene Hemangioblastomas CNS + RETINA

LINDAU (VHL) AD RENAL CELL CA
Cysts internal organs

TUBEROUS AD TS 1/2 Sebaceous adenomas (Angiofibromas of sebaceous glands)

SCLEROSIS o Subependymal nodules = LISCH NODULES
Epilepsy
MR
dysplastic white matter lesions = Hamartomatous lesions skin, CNS,
viscera
Cortical tubers
Shahreen patches (see picture -- -- --- ---
Ash-leaf spot (hypomelanic, light patches,
Wood's)
RENAL ANGIOMYOLIPOMAS
Heart Defect
RHABDOMYOMAS

23
OSTEOGENESIS 7 or 17 COL1A1/2 type 1 procollagen **PLEIOTROPY** - blue sclerae seemingly unrelated to fx
IMPERFECTA - locus **LOCUS OF HETEROGENEITY** 2 diff single chromosome
("BRITTLE hetero- mutationssame dz
geneity Looks like child abuse Multiple fx w/ minimal trauma
BONE")
AD BLUE SCLERA (translucent CT over choroid)
Hearing loss (ABNL MIDDLE EAR BONE)
DENTAL lack dentin
*remember
I = Bone, Skin, tendon
Type ONE = BONE
EHLERS-DANLOS AD and COL3A Hyperextensible skin
AR Type 3 collagen Easy BRUISING/Bleeds
many Hypermobile jts
types **6 types w/ varying inheritance/severity (AD or AR)
+/- a/w:
Joint dislocation
BERRY ANEURYSM
Organ rupture

*remember
III = Reticulin = skin, vessels, uterus, fetal tissue, granulation tissue
Type III = ThreE D defective in Ehlers-Danlos
ATAXIA- Chro- AR Heterogenous, but marked by neurodegeneration (ataxia) +
TELANGIECTASIA mos + chr 7 + 14, ATM (PI3 kinase) telangiectasia (2/2 dilation vessels)
chrom- that phosphorylate >700 - sino-pulm infections
atid proteins in DNA repair* inc. r/o CA, sensitive to xrays/radiation
breaks p53 + BRCA-1 tumor supp
w/ ( chrs correspond to = TCR + Ig
rearra reg)**
ngmt
(WERNERS) AR WS gene helicase error Aging, thin, tight, scleroderma-like skin
muscle, wrinkle, hyperkeratosis
Cataracts, osteoporosis, arteriosclerosis, CA, DM
Japan, M=F
FANCONI AR 11 genes DNA repair, ROS BM fail w DNA repair defect
vulnerability, Cell cycle - petechiase, bruise, pallor, caf-au-lait
dysregulation - infection, fatigue
- aplastic anemia (pancytopenia), leukemia, solid tumors (CA liver, neck,
esophagus, vulvar)
- Tx symptoms (anemia/leukemia, etc)
XERODERMA AR Excision endonuclease thymine UV light sens freckles, skin CA (1,000x), corneal ulcerations
PIGMENTOSUM dimer repair incidence Japan
Tx: 1. retinoids - CA but irreversible calcification tendons/ligaments
- acitretin treats keratoses, also used in psoriasis
2. 5-FU (pyramidine analog antimetabolite)

Normal gene thymine dimer repair via nick PDE bond on strand w/ dimer on
both sides + removes
Defect dimers persist
BREAST CA AD BRCA 1 (2 = ovarian/ prostate/ 60-80% r/o serous adenoCAs
pancreatic)
ALS AD SOD1 copper/zinc superoxide
dismutase

24
MENKE'S X- ATP7A ATP-dependent copper Ehlers-Danlos type 4 "collagen" connection is due to requirement copper
(TYPE 4 EHLERS- linked transport protein co-factor for lysyl oxidase (final steps collagenin EC space)
DANLOS) defective copper transport + abnormally activity copper-dependent
enzymes (one of which is lysyl oxidase) with ceruloplasmin levels

-depigmented, lusterless hair = "KINKY HAIR"

- osteoporosis, anemia
- facial/ocular/vascular/cerebral manifestations (think head-up + vessels,
which always comes with collagenous dz)

"A 4mth old boy appeared healthy at birth but now has poor growth,
feeding and delayed developmental milestones. PE shows listlessness +
matted, sparse + very pale hair"
HUNTINGTON 4 CAG triNT repeat Depression
AD Progressive dementia
Choreiform
CAUDATE ATROPHY
GABA + ACh in brain
20-50yo

SICKLE CELL AR
FAMILIAL APC - tumor suppressor gene
ADENOMATOUS
POLYPOSIS

RETINOBLASTOMA AD w/ Rb - tumor suppressor gene

variable **ALSO IN OSTEOSARCOMA**
pene-
trance
2+
WILLIAM'S 7q Elastin (microdeletion) Elfin facies, HYPER-Ca 2/2 sensitivity to vitD), good verbal, very friendly,
DISEASE heart issues

ACHONDROPLASIA 3 FGF-R3 Dwarf, short limbs, but normal head/trunk size

AD - cell signaling defect **a/w advanced paternal age
FAP 5 APC deletion - >puberty, colon covered with polyps
AD - CRC always if not resected /(usually ~40yo)

DUCHENNE'S X- Dystrophin DUCHENNE = frame-shift = DELETION dystrophin gene accelerated

MUSCULAR linked muscle breakdown
DYSTRPHY VS. LARGE DELETION single gene vs. - Onset <5yo = pelvic girdle weakness (need UE helpto get out of
BECKER'S pt mutation same gene chair sign = COWERS) progresies superiorly
- PSEUDOHYPERTROPHY CALF muscles 2/2 fibrofatty replacement
muscle
- Cardiac Myopathy
- Dx = CPK, muscle biopsy
- **Dystrophin Gene (DMD) = helps anchor muscle fibers (skeletal +
cardiac)
- LONGEST known human gene rate spontaneous mutation
BECKERS = IN-frame deletion or insertion
- less severe, some functional gene made
- Onset adolescence early adult

**SUBCLINICAL FEMALES** - heterozygous carriers have degeneration

fibers
ADPKD 16 APKD1 (90%) *ALWAYS BL, massive kidneys d/t multiple large cysts
AD *Present flank pain, hematuria,HTN, RF

25
FAMILIAL LDL 2/2 defect/absent LDL-R
HYPERCHOLESTER **Heterozygotes (1/500) = 300
OLEMIA (TYPE IIA) **Homozygotes (RARE) = 700+
- Severe atherosclerotic dz early in life
- TENDON XANTHOMAS (achilles)
- MI <20yo

HEREDITARY BLOOD VESSELS

HEMORRHAGIC - Telandiectasias
TELANGIECTASIA - Recurrent epistaxis
(OSLER-WEBER- - Skin discoloration
RENDU) - AVMs

HEREDITARY Spectrin OR Ankyrin Spheroid RBVs d/t hemolytic anemia + SPLENECTOMY CURATIVE
SPHEROCYTOSIS MCHC
MYOTONIC 19 CTG triNT in protein kinase MyoTonic = CTG (vs. CGG = fracile X)
DYSTROPHY AD Clinically UNIQUE:
(can be - Weakness
spont.) - Atrophy
- Myotonia (tonic ctz)
- Head+neck often most weak/atrophic
WONT RELEASE HAND WHEN YOU SHAKE
FRAGILE X X- CGG triNT repeats r/o CHROMOSOMAL BREAK
nd st
linked FMR-1 gene - 2 MCC MR (1 = Downs)
- MACROCHORDISM (big testes), long face, LARGE + everted ears,
(xq27) autism, MVP* (Fragile X = Xtra larges teses/jaws/ears)
IN ADDITION to TRI-nt rpt exp, also role of DNA METHYLATION

Dx = >4% metaphase chromosomes must show specific break-pt on X chr

(percentage above 4% does NOT correlate w/ severity MR)

FINAL MIX GENETICS, MOBIO, CELL BIO

Child with poor eye contact and HAND FLAPPING Fragile X
CGG repeat
1/2
If 1/100 ppl have disease A which is AR, what is (1/100) = 1/10 = p
carrier population freq? 1 1/10 = 9/10 = q
2pq = 2(9/10)(1/10) = 18/100
Calculating changes in volume with compartments C1V1 = C2V2 (before and after change in environment)
of different salt concentrations Key is that Mass = C x V and this remains constant
Mediator of lysosomal enzyme delivery to Clathrin-coated vesicles
lysosomes
Given phenotype that is related to inheritable PCR
tumor, best lab test to determine if it is due to
- the cells in an inherited disease will all show the different (mutant)
inherited mutation or sporadic mutation?
DNA allele size as all cells came from same progeny
- cells in sporadic disease will only have abnormal IF you are testing
cells from tumor tissues all other, non-involved cells will only
provide alleles of normal size
2 ways that a female can exhibit phenotype of X- 1. Concomitant Turner 45X,0 (hints include a short stature, female 2 sex
linked recessive mutation characteristics) this is similar to being male with only 1 X copy
2. 2 copies mutant X gene must be a disease that does not affect fathers
fertility, such as G6PD
Common sex chromosome aneuploidy that would Klinefelters XXY only ones with two Xs, thereby leading to inactivation of
have fetal tissue expressing Barr bodies one (Barr)
nd
- NOT Turners 45XO (even though this is female missing 2 x chr means no
Barr)

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Type of chromatin in
mitotically dividing cell
Part of cell cycle where triNT repeats in number
Adolescent boy with
recent h/o burning +
tingling of hands
found t have corneal
opacities +
angiokeratomas
(benign cutaneous
lesion of capillaries = small marks red/blue color
)
Cellular component mitotic spindle
Cellular component microvilli
Cellular component cilia
Child diagnosed with an AD disease (e.g. Marfans)
with no family history what is most likely cause?
What does CREB, SP-1, RNA polymeras, + steroid
receptor have in common
If membrane protein seen in RER but not
membrane or cytoplasm
Infant with hyperplastic gums, lethargy,
misshapen long bones, restricted jt movements,
st
corneal clouding, parents are 1 cousins
Protein critical in formation + maintenance
junctional complexes such as the tight junctions
between enterocytes
Action of hammerhead ribozymes
Gas that diffuses fastest across lipid membrane
Effect of a mutation AG CG at 3 end eukaryotic
gene intron
Listless infant with matted, sparse, pale hair, poor
growth, developmentald delay
Substrate in synthesis of carbohydrate chains that
are transferred to protein component of
glycoproteins such as albumin
Hexosaminisae A deficiency
Capping of mRNA
Heterochromatin (closed/wrapped; euchromatin = open for active
transcription)
S (synthesis)
Fabrys
Boy = x-linked
Microtubule
ACTIN (+ myosin by extension)
Microtubule (9+2 arrangement dynein think Kartageners)
New mutation transmitted by one parent to affected child
All are TFs or modulators of transcription on DNA for regulation of protein
synthesis
Misfolding ubiquination + degradation path (proteasome)
I-cell disease
Defective phosphorylation of mannose moieties lyosomal enzymes not
targeted to lysosome = serum levels acid hydrolases + glycosylases
E-cadherins
Occludins = zona occlude
Desmogleins = specific junction protein in epithelial cells (pemphigus vulgaris
w mouth ulcerations)
Degrade mRNA (catalase activity) of which they have homologous sequence
(to bind)
CO2, followed by O2, then all others (e.g. nitrogen)
Abnormal splicing
AG = highly conserved (invariant)) spliceasome acceptor site sequence at 3
end all introns (matches this with preceding 5 GT (GU in RNA) seq)
activity LYSYL OXIDASE
= MENKES X-LINKED (Ehlers Danlos type 4, ATP7A mutation)
- defect copper transport = activity Cu-dependent enzymes with
ceruloplasmin levels
**DEPIGMENTED LISTLESS/KINKY HAIR is biggest tip off
Dolichol
TAY-SACHS
Cherry red macule without hs-megaly (N-P)
st
Occurs immediately after synth 1 30 NTs (e.g. before transcription even
finishes since read 53 will be done earliest)
- GTP condenses w/ available 5 diphosphate on growing RNA chain
forms GUANINE CAP
- Cap recognized during protein synteshsi
- Protects RNA from degradation
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 cytochrome b5 reductase
Selenium deficiency
2 congenital diseases with MR + skin
hypopigmentation (not neurocutaneous)
= IRON-dependent enzyme, aka NADH methemoglobin reductase major
pathway that reduces methemoglobin which forms spontaneously with
oxidative stress etc.
Deficient METHEMOGLOBINEMIA cyanosis (nl amt <1%)
- metHb = OXIDIZED form Hb (Ferrous Fe Ferric Fe ) = affinity O2
2= 3+
(curve shifts LEFT) unloading O2 at tissue (blood has O2-carrying
capacity, turns brown)
can arise in pts with PK def d/t impaired NADH production = ESSENTIAL
COFACTOR of enzyme or in G6PD def d/t impaired NADPH cofactor
* (Also is recessive genetic defect in chr or can occur with abnl Hb variants,
e.g. HbM or HbH)
*remember oxidized = less electrons, reduced = more, so Fe3+ has MORE
positive charge/less electrons = oxidized*
CAUSES OF ACQUIRED METHEMOGLOBINEMIA
1. Exogenous oxidizing Rx + metabolites - rate formation metHb
overwhelms protective systems = acute metHb levels
o benzocaine
o dapsone
o nitrates
2. ABX
a. TMP
b. Sulfas
c. Dapsone
3. Local anesthetics
a. Articaine
b. prilocaine
4. ANILINE DYES (polyurethane, indigo; normally a/w BLADDER CA)
5. Metoclopromide DA-blocking Antiemetic (D2-R antagonist with mild
5HT-3 antagonism + some anti-muscarinic effects)
a. ALSO gastric emptying in gastroparesis good
antiemetic for DM pts); stimulates lactation)
b. Parkinsonian SEs, contra in SBO
6. Chlorates, bromates
7. Nitrate ingestion (bismuth nitrate) BLUE BABY SYNDROME in
babies drinking contaminated water from FERTILIZER nitrates
a. Babies also get from dehydrration 2/2 diarrheal GE, sepsis,
topical anesthetics w/ benzocaine, prilocaine (benzocaine
also often in baby teething gels applied to gum/throat)
*Tx Methylene Blue IV (or flavin) then normal saline flush (= artificial e-
acceptor for NADPH methemoglobin reductase (enzyme function at 5x nl)
NADPH generated via HMP shunt
RESTORES Fe3+ Fe2+ =normal/reduced O2-carrying state)
levels glutathione peroxidase
MYOPATHY + CM
MENKES (E-D type 4, x-linked Cu-enzyme def., lyosyl oxidase)
PKU
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EMBRYO

PATHOLOGY + MISCELLANEOUS
Analine dye association URINARY BLADDER CA industrial workers (also shistosomal parasites outside of
US with general RFs = smoking, exposure to certain chemicals + parasiteic infection)
- Also a/w methomologbloinemia

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Points of exit for Trigeminal nerve
Standing Room Only:
V1 - Superior orbital fissure
V2 - foramen Rotundum
V3 - foramen Ovale
Extensor Compartment of the Arm
Beer Brachioradialis
Eating CReoLe Extensor Carpi Radialis Longus
Eating CRaB Extensor Carpi Radialis Brevis
Eating Dog Extensor Digitorum
Eating Dog's Mother Extensor Digiti Minimi
Even Cathy's Underwear Extensor Carpi Ulnaris

Great vessels- ABC'S of the aortic arch:

Aortic arch, Brachiocephalic trunk, the left common Carotid, and the left Subclavian artery
Thoracic duct
The duck is between two gooses:
duck = thoracic duct
2 gooses = azyGOUS vein and esophaGOUS
Order of structures in groin (from lateral to medial)
NAVEL
Nerve, Artery, Vein, Empty space, Lymphatics
Carpal bones
Some Lovers Try Positions That They Can't Handle
Scaphoid, Lunate, Triquetrum, Pisiform, Trapezoid, Trapezium, Capitate, Hamate.
Gluteal Muscles
Rhmye Time: "Tensor Fasciae Latae, Gluteus Med & Min...first abduct the femur, then rotate it in."
All other gluteal muscles are lateral rotators of the femur.
BONUS: Tensor Fasciae Latae, Gluteus Minimus, and Gluteus Maximus are all innervated by the Inferior Gluteal Nerve.
Radial nerve
"BEST"
It innervates the Brachioradialis, Extensors, Supinator, Triceps.
Median nerve
"LOAF"
It innervates the Lateral 2 Lumbricals, Opponens pollicis, Abductor pollicis brevis, Flexor pollicis brevis.
Brachial Plexus Lesions
"DR. CUMA"
D - wrist Drop (is caused by...)
R - Radial nerve lesion
C - Claw hand (is caused by...)
U - Ulnar nerve lesion
M - Median nerve (lesion causes...)
A - Ape hand
Mitosis
People Meet And Talk, or
PMAT
Prophase, Metaphase, Anaphase, Telophase.

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