Term
Chromatin structure
normal vs. mitosis |
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Definition
Negatively charged DNA loops twice around histone octamer to form nucleosome bead
Histone: 2 each of the positively charged H2A, H2B, H3, and H4
H1 ties nucleosomes together in string
In mitosis - DNA condenses to form mitotic chromosomes |
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Term
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Definition
condensed, transcriptionally inactive
HC = highly condensed |
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Term
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Definition
| Less condensed, transcriptionally active |
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Term
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Definition
Purines: A & G - 2 rings (pure as gold)
Guanine has a ketone
Pyrimidines: C, T & U - 1 ring (Cut the PY)
Thymine has a methyl
deamination of Cytosine = uracil |
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Term
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Definition
A
G
Guanine has a ketone
amino acids necessary for purine synthesis: Glycine, Aspartate, Glutamine |
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Term
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Definition
C (deamination of Cytosine = uracil)
U
T (Thymine has a methyl) |
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Term
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Definition
G-C bond: 3H bonds (stronger)
A-T bond: 2H bonds
Increased GC content increases melting temperature |
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Term
| Purine synthesis requirements |
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Definition
AA: Glycine, aspartate, glutamine
CO2
N10 Formyl tetrahydrofolate
made from IMP precursors |
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Term
| Pyrimidine synthesis requirements |
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Definition
Carbamoyl phosphate
aspartate
Made from orotate precursor with PRPP added later |
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Term
| Nucleoside vs nucleotides |
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Definition
Nucleoside = base +ribose
Nucleotide = base+ribose+phosphate, linked by 3-5 phosphodiester bond |
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Term
| DNA directed Antineoplastic and antibiotic drug mechanism |
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Definition
interfere with NT synthesis
Hydroxyurea - inhibits ribonucleotide reductase
6-Mercaptopurine (6MP) - blocks de novo purine synthesis
5-fluorouracil (5-FU) - inhibits thymidylate synthase (decrease dTMP)
Methotrexate (MTX) - inhibits dihydrofolate reductase (decreases dTMP)
Trimethoprim - inhibits bacterial dihydrofolate reductase (decreases dTMP) |
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Term
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Definition
| inhibits ribonucleotide reductase |
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Term
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Definition
| blocks de novo purine synthesis |
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Term
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Definition
| inhibits thymidylate synthase (decreased dTMP) |
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Term
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Definition
| inhibits dihydrofolate reductase (decreases dTMP) |
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Term
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Definition
inhibits bacterial dihydrofolate reductase
(decreases dTMP) |
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Term
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Definition
| substituting purine for purine or pyr for pyr |
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Term
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Definition
| substituting purine for pyr or vice versa |
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Term
| Genetic code features (4) |
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Definition
1. unambiguous - each codon specifies only 1 amino acid
2. degenerate/redundant - more than one codon may code for the same aa (exception: methionine encoded by only 1 codon (AUG))
3. commaless, nonoverlapping - read from a fixed starting point as a continuous sequence of bases (some viruses are an exception)
4. universal - conserved throughout evolution (exceptions include mitochondria, archaebacteria, mycoplasma, and some yeasts) |
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Term
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Definition
Silent - same aa, often base change in 3rd position of codon (tRNA wobble)
missense - changed aa (conservative - new aa is similar in chemical structure)
nonsense - change resulting in early stop codon
frame shift - change resulting in misreading of all nucleotides downstream, usually resulting in truncated nonfunctional protien
severity of damage: nonsense>missense>silent |
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Term
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Definition
more complex than prokaryotic process, many of the same enzymes
semiconservative, both continuous and discontinuous (Okazaki fragment) synthesis
replication begins at consensus sequence of base pairs |
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Term
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Definition
particular sequence in genome where DNA replication begins
prokaryotes - single
eukaryotes - multiple |
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Term
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Definition
| Y-shaped region along DNA template where leading and lagging strands are synthesized |
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Term
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Definition
unwinds DNA template at replication fork
fluoroquinolones - inhibit DNA gyrase (specific prokaryotic topoisomerase) |
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Term
| Single stranded binding proteins |
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Definition
| prevent strands from reannealing |
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Term
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Definition
| create a nick in the helix to relieve supercoils created during replication |
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Term
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Definition
| makes an RNA primer on which DNA polymerase III can initiate replication |
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Term
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Definition
prokaryotic only
elongates leading strand by adding deoxyNT to the 3' end. Elongates lagging strand until it reaches primer of preceding fragment.
3'-5' exonuclease activity proofreads each added nucleotide
5'-3' synthesis 3-5' proofreading exonuclease |
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Term
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Definition
| inhibits DNA gyrase (specific prokaryotic topoisomerase) |
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Term
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Definition
prokaryotic only
degrades RNA primer and fills in the gap with DNA
excises RNA primer with 5'-3' exonuclease |
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Term
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Definition
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Term
| Nucleotide excision repair |
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Definition
specific endonucleases release the oligonucleotide containing damaged bases
DNA pol fills and ligase reseals gap
mutated in xeroderma pigmentosum (dry skin with melanoma and other cancers, "children of the night") which prevents repair of thymidine dimer |
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Term
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Definition
specific glycosylases recognize and remove damaged bases
AP endonuclease cuts DNA at pyrimidine site, empty sugar is removed and gap is filled and resealed |
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Term
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Definition
unmethylated, newly synthesized string is recognized, mismatched NT removed, and gap filled and resealed
mutated in hereditary nonpolyposis colorectal cancer |
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Term
| Xeroderma pigmentosum mutation |
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Definition
| mutated nucleotide excision repair |
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Term
| Hereditary nonpolyposis colorectal cancer mutation |
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Definition
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Term
| Nonhomologous end joining |
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Definition
brings together 2 ends of DNA fragments
no requirement for homology |
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Term
| DNA and RNA and Protein synthesis direction |
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Definition
5'-3'
5' of incoming NT bears triphosphate (energy source for bond)
3' hydroxyl of nascent chain is target
mRNA is read 5'-3'
Protein synthesis is N to C |
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Term
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Definition
rRNA - most abundant
mRNA - longest
tRNA - smallest
Rampant, massive, tiny |
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Term
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Definition
AUG (rarely GUG)
Eukaryote - codes for methionine, which may be removed before translation is completed
prokaryotes - codes for formyl-methionine (f-Met) |
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Term
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Definition
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Term
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Definition
site where RNA polymerase and multiple other transcription factors bind to DNA upstream from gene locus (AT-rich upstream sequence with TATA and CAAT boxes)
mutation commonly reults in dramatic decrease in amount of gene transcribed |
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Term
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Definition
Stretch of DNA that alters gene expression by binding transcription factors
can be located close to, far from, or even within (in an intron) the gene whose expression it regulates |
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Term
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Definition
| site where negative regulators (repressors) bind |
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Term
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Definition
EUKARYOTES:
RNA pol I -makes rRNA
RNA pol II - makes mRNA
RNA pol III - makes tRNA
no proofreading function, but can initiate chains.
RNA pol II opens DNA at promoter site
alpha-amanitin (found in death cap mushrooms) inhibits RNA pol II
PROKARYOTES:
1 RNA polymerase (multisubset complex) makes all 3 kinds of RNA |
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Term
| RNA processing (eukaryotes) |
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Definition
occurs in nucleus after transcription
1. capping on 5' end (7-methylguanosine)
2. polyadenylation on 3' end (=200 A's): AAuAAA = polyadenylation signal, poly-A polymerase does not require a template
3. splicing out of introns
initial transcript is called heterogeneous nuclear RNA (hnRNA)
capped and tailed transcript is called mRNA
only processed RNA is transported out of nucleus |
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Term
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Definition
occurs in eukaryotes
1 - primary transcript (GU---A---AG) combines with snRNP's and other proteins to form splicesome
2. Lariat shaped intermediate is generated (GU (lariat) A --- AG)
3. Lariat is released to remove intron precisely and join 2 exons |
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Term
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Definition
| combination of different exons to make unique proteins in different tissues (e.g B-thalassemia mutations) |
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Term
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Definition
75-90 nt
Secondary structure: cloverleaf form, anticodon end is opposite 3' aminoacyl end.
CCA at 3' end with base, covalently bound |
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Term
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Definition
Uses ATP
aminoacyl-tRNA synthetase (1 per aa, matchmaker, uses ATP) scrutinizes aa before and after it binds to tRNA
Incorrect bond hydrolyzed
aa-tRNA bond has energy for formation of peptide bond
mischarged tRNA reads usual codon but inserts wrong aa
tetracyclines - bind 30S subunit of prokaryotes preventing attachment of amionacyl-tRNA |
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Term
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Definition
| bind 30S prokaryote subunit preventing attachment of aminoacyl-tRNA |
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Term
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Definition
3rd nt position of codon
due to degeneracy (redundancy) of genetic code |
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Term
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Definition
Initiation - Elongation - Termination
uses GTP |
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Term
| Protein Synthesis Initiation |
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Definition
Activated by GTP hydrolysis
initiation factors (eIFs) help assemble the 40S ribosomal subunit with the initiator tRNA and are released when the mRNA and ribosomal subunit assemble with the complex |
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Term
| Proteine Synthesis Elongation |
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Definition
Uses GTP
1. aminoacyl-tRNA binds to A site (except for initiator methionine)
2. Peptidyltransferase catalyzes peptide bond formation, transfers growing polypeptide to aa in A site
3. Ribosome advances 3 nt toward 3' end of RNA, moving peptidyl RNA to P site (translocation)
A = incoming aminoacyl tRNA
P = accommodates growing peptide
E = holds empty tRNA as it exits |
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Term
| Antibiotics that inhibit protein synthesis |
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Definition
Aminoglycosides - inhibit formation of the initiation complex and cause misreading of mRNA
Chloramphenicol - inhibits 50S peptidyltransferase
Macrolides - bind 50S, blocking translocation
Clindamycin - binds 50S, blocking translocation |
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Term
| Energy requirements of translation |
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Definition
tRNA aminoacylation: ATP --> AMP (2 phosphoanhydride bonds)
Loading tRNA onto ribosome: GTP --> GDP
Translocation: GTP --> GDP
Total energy expenditure: 4 high energy phosphoanhydride bonds |
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Term
| Posttranslational modifications |
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Definition
trimming: removal of N or C terminal propeptides from zymogens to generate mature proteins
Covalent alterations: phosphorylation, glycosylation, hydroxylation
proteasomal degradation: attachment of ubiquitin to defective proteins to tag them for breakdown |
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Term
| Methods of regulating enzymes (7) |
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Definition
concentration alteration (synthesis or destruction)
covalent modification (phosphorylation)
proteolytic modification (zymogen)
allosteric regulation (feedback inhibition)
ph
temperature
transcriptional regulation (steroid hormones) |
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Term
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Definition
regulated by: cyclins, CDKs, and tumor suppressors
Mitosis (prophase, metaphase, anaphase, telophase) - shortest
Interphase includes all of the following:
G1/G0
S
G2 |
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Term
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Definition
| cyclin dependent kinases, constitutive and inactive |
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Term
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Definition
regulatory proteins that control cell cycle events
phase specific
activate CDKs |
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Term
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Definition
| must be both activated and inactivated for cell cycle to progress |
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Term
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Definition
Rb and p54 normally inhibit G1 to S progression
mutations in these genes results in unrestrained growth |
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Term
cell types
Permanent v stable v labile |
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Definition
permanent - remain in G0, regenerate from stem cells (neurons, skeletal and cardiac muscle, RBCs)
Stable (quiescent) - enter G1 from G0 when stimulated (hepatocytes, lymphocytes)
Labile - never go to G0, divide rapidly with a short G1 (bone marrow, gut epithelium, skin, hair, follicles) |
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Term
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Definition
site of synthesis of secretory (exported) proteins and of N-linked oligosaccharide addition to many proteins
mucus-secreting goblet cells of small intestine and antibody secreting plasma cells are rich in RER
Nissl bodies in neurons synthesize enzymes and peptide neurotransmitters |
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Term
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Definition
unattached to any membrane
synthesize cytosolic and organellar proteins |
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Term
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Definition
site of steroid synthesis and detoxification of drugs and poisons
liver hepatocytes and steroid hormone producing cells of adrenal cortex are rich in SER |
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Term
| Golgi apparatus roles (6) |
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Definition
1. distributes proteins and lipids from ER to plasma membrane, lysosomes, and secretory vesicles
2. modifies N-oligosaccharides on asparagine
3. Adds O-oligosaccharides to serine and threonine residues
4. adds mannose-6-P to specific lysosomal proteins -->targets protein to lysosome (I-cell disease)
5. proteoglycan assembly from core proteins
6. sulfation of sugars in proteoglycans and of selected tyrosine on proteins |
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Term
| vesicular trafficking proteins (3) |
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Definition
COPI - retrograde, golgi --> ER
COP II - anterograde, RER --> cis golgi
Clathrin: trans-golgi --> lysosomes, plasma membrane --> endosomes (receptor mediated endocytosis) |
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Term
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Definition
inclusion cell disease
inherited lysosomal storage disorder
failure of addition of Mannose6P to lysosome proteins (enzymes are not targeted to lysosome and are secreted outside of cell instead)
Coarse facial features, clouded corneas, restricted joint movement, and high plasma levels of lysosomal enzymes
often fatal in childhood |
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Term
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Definition
helical array of polymerized dimers of alpha and beta tubulin
each dimer - 2 bound GTP
incorporated into flagella, cilia, mitotic spindles
involved in slow axoplasmic transport neurons (used as tracks)
grows slowly, collapses quickly
Chediak-Higashi syndrome |
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Term
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Definition
transport cellular cargo toward opposite ends of microtubule tracks
Dynein = retrograde to microtubule (+ to -)
Kinesin = anterograde to microtubule (- to +) |
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Term
| Drugs that act on microtubules |
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Definition
mebendazole/thiabendazole - antihelminthic
Griseofulvin - antifungal
vincristine/vinblastine - anti-cancer
paclitaxel - anti-breast cancer
colchicine - anti-gout |
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Term
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Definition
microtubule polymerization defect resulting in decreased phagocytosis
recurrent pyogenic infections, partial albinism, and peripheral neuropathy |
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Term
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Definition
9+2 arrangement of microtubues
peripheral 9 doublets linked by ATPase axonemal dynein, causing bending of cilium by differential sliding of doublets
Kartagener's syndrome |
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Term
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Definition
immotile cilia due to dynein arm defect
male and female infertility (sperm immotile), bronchiectasis, and recurrent sinusitis (bacteria and particles not pushed out)
associated with situs inversus |
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Term
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Definition
| microvilli, muscle contraction, cytokinesis, adherens junctions |
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Term
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Definition
| cilia, flagella, mitotic spindle, neurons, centriole |
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Term
| Intermediate filaments: (5) |
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Definition
| vimentin, desmin, cytokeratin, glial fibrillary acid proteins (GFAP), neurofilaments |
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Term
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Definition
| Actin and myosin, microtubule, intermediate filaments |
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Term
| Plasma membrane composition |
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Definition
asymmetric fluid bilayer
contains cholesterol (50%), phospholipida (50%), sphingolipids, glycolipids, and proteins
high cholesterol or long saturated fatty acid content causes:
high melting temperature and low fluidity |
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Term
| Immunohistochemical stain (Stain: cell type) (5) |
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Definition
Vimentin - connective tissue
Desmin - muscle
cytokeratin - epithelial cells
GFAP - Neuroglia
Neurofilaments - neurons |
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Term
| Na-K ATPase (location, function, inhibitors) |
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Definition
located in plasma membrane with ATP on cytoplasmic side
1 ATP, 3 Na out, 2K in
during cycle - pump is phosphorylated
Inhibited by
Oubain (binds K site)
Cardiac glycosides (digoxin and digitoxin) - direct inhibition of Na/K ATPase, causing indirect inhibition of Na/Ca exchange --> increased intracellular Ca and increased cardiac contractility |
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Term
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Definition
| inhibits Na/K ATPase by binding to K site |
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Term
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Definition
Digoxin and digitoxin
Directly inhibits Na/K ATPase
indirectly inhibits Na/Ca exchange
Increases intracellular Ca
Increasing cardiac contractility |
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Term
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Definition
Most abundant protein in human body, extensively modified
Organizes and strengthens ECM
Type I (90%) - bone, skin, tendon, dentin, fascia, cornea, late wound repair
Type II - cartilage (including hyaline), vitreous body, nucleus pulposus
Type III (reticulin) - skin, blood vessels, uterus, fetal tissue, granulation tissue
Type IV - basement membrane or basal lamina
Be So Totally Cool, Read Books |
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Term
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Definition
| Bone, skin, tendon, dentin, fascia, cornea, late wound repair |
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Term
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Definition
| Cartilage (including hyaline), vitreous body, nucleus pulposus |
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Term
| Type III collagen (reticulin) |
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Definition
| Skin, blood vessels, uterus, fetal tissue, granulation tissue |
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Term
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Definition
| Basement membrane or basal lamina |
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Term
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Definition
3 chains wound together
Gly-X-Y polypeptide
X and Y are proline, hydroxyproline, and hydroxylysine) |
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Term
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Definition
Inside fibroblast
1. synthesis (RER) - translation of collagen alpha chains (preprocollagen)
2. hydroxylation (ER) or specific proline and lysine residues (requires vitamin C and O2)
3. Glycosylation (ER) - addition of galactose and glucose to pro-alpha-chain lysine residues and formation of procollagen (triple helix)
4. Exocytosis of procollagen into ECM
Outside fibroblast:
5. proteolytic processing - cleavage of terminal regions of procollagen, transforming it into insoluble tropocollagen
6. Cross-linking - reinforcement of many staggered tropocollagen molecules by covalent lysine-hydroxylysine cross linkage (by lysyl oxidase) to make collagen fibrils |
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Term
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Definition
Faulty collagen synthesis
Type III most frequently (Reticulin = skin, blood vessels, uterus, fetal tissue, granulation tissue)
1. Hyperextensible skin
2. tendency to bleed
3. hypermobile joints
6 types, inheritance and severity vary
AD or AR
associated with joint dislocation, berry aneurysms, organ rupture |
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Term
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Definition
genetic bone disorder (brittle bone disease) caused by a variety of gene defects
Most common - AD with abnormal Type I collagen
Incidence = 1:10,000
1. Multiple fractures - may occur during birth
2. Blue sclerae - translucency or CT over choroid
3. Hearing loss (abnormal middle ear bones)
4. Dental imperfections (lack of dentin)
Don't confuse with child abuse
Type II - fatal in utero or in neonate period
Type I collagen - bone, skin, teeth, dentin, fascia, cornea, late wound repair |
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Term
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Definition
variety of gene defects resulting in abnormal type IV collagen (Basement membrane or basal lamina of kidney, ears and eyes)
Most common: X linked Recessive
Progressive hereditary nephritis and deafness
associated with ocular disturbances |
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Term
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Definition
Stretchy protein
Precursor: Tropoelastin with fibrillin scaffolding
Lungs, large arteries, elastic ligaments, vocal cords, ligamenta flava (connect vertebrae --> relaxed and stretched conformations)
Rich in proline and glycine, nonglycosylated forms
Broken down by elastase, which is normally inhibited by alpha1-antitrypsin
Marfans (fibrillin defect) and Emphysema (alpha1 antitrypsin deficiency) |
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Term
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Definition
AD
defect in fibrillin
normally, fibrillin forms scaffolding and combines with tropoelastin to form elastin
CT disorder affecting skeleton, heart, eyes
Tall, arachnodactyly, pectus excavatum, hyperextensive joints, MV prolapse, lens discoloration and subluxation
cystic medial necrosis of aorta --> aortic incompetence and dissecting aortic aneurysm |
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Term
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Definition
alpha1-antitrypsin deficiency
causes excess elastase activity which breaks down elastin |
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Term
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Definition
amplifies desired DNA fragments
1. denaturation
2. annealing
3. elongation
agarose gel electrophoresis - used for size separation of PCR products (smaller molecules travel further) |
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Term
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Definition
DNA sample electrophoresed on a gel
transferred to filter
filter soaked in denaturant
filter exposed to labeled DNA probe that recognizes and anneals to its complementary strand
results in double stranded labeled piece of DNA which can be visualized when filter is exposed to film |
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Term
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Definition
RNA sample electrophoresed on gel
DNA probe used to bind to RNA sample |
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Term
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Definition
Protein sample separated via gel electrophoresis and transferred to filter
labeled antibody used to bind relevant protein |
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Term
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Definition
thousands of nucleic acid sequences arranged in grids on glass or silicon
DNA or RNA probes hybridized to chip and scanner detects relative amount of complementary binding
Used to profile gene expression levels or to detect SNP |
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Term
| Enzyme-Linked immunosorbent assay (ELISA) |
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Definition
Tests for antigen-antibody reactivity
patients blood sample probed with either:
Test antigen (coupled with color-generating enzyme) - to see if immune system recognizes it
2. Test antibody (coupled with color-generating enzyme) - to see if a certain antigen is present
Presence of target substance, test solution has intense color reaction, indicating positive result
Sensitivity and specificity approach 100%
can have false + and false - though |
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Term
| Fluorescence in situ hybridization (FISH) |
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Definition
Fluorescent DNA or RNA probe binds to specific gene site of interest
used for specific localization of genes and direct visualization of anomalies (microdeletion) at molecular level (when deletion is too small to be visualized by karyotype)
Fluorescence = gene is present, no fluorescence = gene is deleted |
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Term
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Definition
production of recombinant DNA molecules that is self-perpetuating
1. DNA fragments inserted into bacterial plasmids with antibiotic resistance genes and then selected for and amplified
2. restriction enzymes cleave DNA, allowing for insertion of fragment into plasmid
3. Tissue mRNA is isolated and exposed to reverse transcriptase, forming a cDNA (no introns) library |
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Term
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Definition
dideoxyNT halt DNA polymerization at each base --> sequences of various lengths encompassing entire original sequence
terminated fragments are electrophoresed and original sequence deduced |
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Term
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Definition
1. random insertion of gene into mouse genome (constitutive)
2. Targeted insertion or deletion of gene through homologous recombination with mouse gene (conditional)
Gene can be manipulated at specific developmental points using an inducible Cre-lox system with an antibiotic-controlled promoter (to study a gene whose deletion causes embryonic lethality) |
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Term
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Definition
dsRNA is synthesized that is complementary to the mRNA sequence of interest
When transfected into human cells, dsRNA separates and promotes degradation of target mRNA, knocking down gene expression |
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Term
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Definition
metaphase chromosomes stained, ordered, and numbered according to morphology, size, arm-length ratio and banding pattern
Sample from: blood, bone marrow, amniotic fluid, placental tissue
used to diagnose chromosomal imbalances (autosomal trisomies, microdeletions, sex chromosome disorders) |
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Term
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Definition
| neither of 2 alleles is dominant (blood groups) |
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Term
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Definition
| Nature and severity of the phenotype varies from 1 individual to another |
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Term
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Definition
| not all individuals with mutant genotype show mutant phenotype |
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Term
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Definition
1 gene has > 1 effect on individual's phenotype
PKU - any mutation in large gene can cause either reduced or zero phenylalanine to tyrosine conversion resulting in a number of phenotypes |
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Term
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Definition
At single locus, only 1 allele is active (the other is silenced through imprinting or inactivation by methylation)
Therefore deletion of active allele -->disease
differences in phenotype depend on whether the mutation is of maternal or paternal origin
Prader willi syndrome (silencing of maternal genes in conjunction with loss of normally active paternal genes) - MR, hyperphagia, obesity, hypogonadism, hypotonia
Angelman's syndrome (paternal imprinting and loss of normally active maternal genes)- happy puppet syndrome, MR, seizures, ataxia, inappropriate laughter
Both syndromes due to inactivation or deletion of genes on chr 15
can also occur as result of uniparental disomy |
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Term
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Definition
| severity of disease worsens or age of onset of disease is earlier in succeeding generations (Huntingtons) |
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Term
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Definition
if patient inherits or develops mutation in tumor suppressor gene, other allele must also be damaged before cancer develops
not true of protooncogenes |
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Term
| Dominant negative mutation |
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Definition
Exerts a dominant effect
heterozygote produces nonfunctional altered protein that also prevents normal gene product from functioning
collagen production |
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Term
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Definition
tendency for certain alleles at 2 linked loci to occur together more often than expected by chance
population measurement (not family)
varies by population |
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Term
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Definition
occurs when cells in body have different genetic makeup
lyonization - randome X inactivation in females |
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Term
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Definition
| mutations at different loci can produce same phenotype (albinism) |
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Term
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Definition
presence of both normal and mutated mtDNA, resulting in variable expression in mitochondrial inherited diseases
leber optic atrophy |
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Term
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Definition
| offspring receives 2 copies of chromosome from 1 parent and no copies from the other parent |
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Term
| Hardy-Weinberg population genetics |
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Definition
if a population is in Hardy Weinberg equilibrium and p and q are separate alleles, then:
disease prevalence: p^2 +2pq +q^2 =1
allele prevalence: p+q=1
the prevalence of an X linked recessive disease in males is q and in females is q^2
Assumptions
1. no mutations
2. no selection
3. randome mating
4. no migration |
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Term
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Definition
often structural gene defects
many generations, M, F
often pleiotropic (1 mutation many phenotypes), present clinically post puberty
FHx crucial |
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Term
|
Definition
25% of offspring from 2 carrier parents are affected
often enzyme deficiencies
usually only 1 generation
commonly more severe than dominant d/o, childhood presentation |
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Term
|
Definition
transmitted through both parents
M or F offspring of affected mother
All F or affected father
Hypophosphatemic rickets - formerly known as Vit-D resistant rickets, inherited, increases phosphate wasting at proximal tubule and causes rickets like presentation |
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Term
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Definition
sons of heterozygous mothers have 50% chance of being affected
no M to M transmission
commonly more severe in M
Heterozygous females may be affected |
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Term
| Mitochondrial inheritance |
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Definition
transmitted only through mother, all offspring affected females may show signs of disease
variable expression due to heteroplasmy (heterogeneous presence of mutated and normal mitochondria)
mitochondrial myopathies, leber's optic neuropathy - degeneration of retinal ganglion cells and axons, leads to acute loss of central vision |
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Term
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Definition
AD
cell signaling defect of fibroblast growth factor receptor 3
dwarfism, short limbs, with normal trunk and head
associated with advanced paternal age |
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Term
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Definition
AD
adult polycystic kidney disease
always bilateral, massive enlargement of kidneys due to multiple large cysts
flank pain, hematuria, HTN, progressive renal failure
90% due to mutation in APKD1 on chr 16
associated with polycystic liver disease, berry aneurysms, MV prolapse
infantile form is recessive |
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Term
| Familial adenomatous polyposis |
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Definition
AD
colon becomes covered with adenomatous polyps after puberty
Colon cancer 100% without resection
Deletion of APC gene on Chr. 5 |
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Term
| Familial hypercholesterolemia (hyperlipidemia type IIA) |
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Definition
AD
elevated LDL due to defective or absent LDL receptor
heterozygotes (1:500) have cholesterol 300 mg/dL
Homozygotes - 700+ mg/dL
severe atherosclerotic disease early in life, tendon xanthomas (achilles)
MI may develop before age of 20 |
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Term
| Hereditary hemorrhagic telangiectasis (Osler-Weber-Rendu syndrome) |
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Definition
AD
disorder of blood vessels
findings: telangiectasis, recurrent epistaxis, skin discolorations, AVM |
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Term
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Definition
AD
spheroid erythrocytes due to spectrin (cytoskeletal protein) or ankyrin (attaches integral membrane proteins to spectrin-actin based membrane skeleton) defect
hemolytic anemia
increased MCHC
splenectomy is curative |
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Term
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Definition
AD
trinucleotide repeat disorder (CAG), on chr 4
findings: depression, progressive dementia, choreiform movements, caudate atrophy, decreased levels of GABA and ACh
present between 20 and 50 |
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Term
| Multiple Endocrine Neoplasias |
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Definition
AD
familial tumors of endocrine glands
I - pituitary, parathyroid, pancreas
II - pheochromocytoma, MTC, PTH
IIb - pheo, MTC, neuroma
II and III - associated with RET gene |
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Term
| Neurofibromatosis type I (von Recklinghuasens) |
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Definition
AD
17q
cafe-au-lait spots, neural tumors, Lisch nodules (pigmented iris harmatomas), skeletal disorders (scoliosis), optic pathway gliomas, pheo, increased tumor susceptibility |
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Term
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Definition
AD
Chr 22 NF2 gene
bilateral acoustic neuroma, juvenile cataracts |
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Term
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Definition
AD
facial lesions (adenoma sebaceum), hypopigmented ash leaf spots on skin, cortical and retinal hamartomas, seizures, MR, renal cysts and renal angiomyolipomas, cardiac rhabdomyomas, increased incidence of astrocytomas
incomplete penetrance, variable presentation |
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Term
| von Hippel-lindau disease |
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Definition
AD
Chr 3p, deletion of VHL gene (tumor suppressor)
causes constitutive expression of HIF (transcription factor) and activation of angiogenic growth factors
hemangioblastomas of retina/cerebellum/medulla
50% develop multiple bilateral renal cell carcinomas and other tumors |
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Term
| Autosomal Recessive disease |
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Definition
albinism
ARPKD (infantile polycystic)
CF
glycogen storage diseases
hemochromatosis
mucopolysaccharidoses (except Hunters)
phenylketonuria
sickle cell anemias
sphinolipidoses (except Fabry's)
thalassemias |
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Term
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Definition
AR, most common lethal genetic disease in Caucasians
Chr. 7, CFTR gene, commonly phe508 deletion
CFTR channel actively secretes Cl- in lungs and GI tract and actively reabsorbs Cl-from sweat
defective Cl- channel --> secretion of abnormally thick mucus that plugs lungs, pancreas, and liver --> recurrent pulmonary infections (pseudomonas and S. aureus), chronic bronchitis, bronchiectasis, pancreatic insufficiency (malabsorption and steatorrhea), meconium ileus in newborns, increased concentration of Cl ions in sweat test is diagnostic
Males: infertile, bilateral absence of vas deferens
fat soluble vit deficiencies (DEAK)
can present as failure to thrive in infancy
Tx: N-acetylcysteine to loosen mucous plugs (cleaves disulfide bonds within mucous glycoproteins) |
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Term
| X linked recessive disorders |
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Definition
Be Wise Fool'd GOLD Heeds False Hope
Bruton's agammaglobulinemia
Wiskott-Aldrich syndrome
Fragile X
G6PD deficiency
Ocular albinism
Lesh-Nyhan syndrome
Duchennes (and Beckers) MD
Hemophilia A and B
Fabry's disease
Hunter's sundrome
female carriers rarely affected due to random x inactivation |
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Term
| Duchenne's Muscular dystrophy |
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Definition
X-linked frame shift-mutation
deletion of dystrophin gene (longest known gene, increased rate of spontaneous mutation)
accelerated muscle breakdown
Weakness begins in pelvic girdle and progresses superiorly
Pseudohypertrophy of calf muscle due to fibrofatty replacement of muscle
cardiac myopathy
Gower's maneuver (use upper extremities to help stand)
onset before 5 y.o.
Dystrophin helps anchor muscle fibers, primarily in skeletal and cardiac muscle
Dx: increased CPK and muscle biopsy |
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Term
| Becker's Muscular dystrophy |
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Definition
X-linked mutated dystrophin gene
less severe than Duchennes
onset in early adult/adolesence
Dystrophin is longest known gene --> increased rate of spontaneous mutation
Dystropin helps anchor muscle fibers (skeletal and cardiac)
Dx with increased CPK and muscle biopsy |
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Term
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Definition
X-linked defect
TriNT repeat (CGG)
disrupted methylation and expression of FMR1 gene
associated with Chr breakage
2nd most common cause of genetic MR (after downs)
Macro-orchidism, long face with large jaw, large everted ears, autism |
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Term
| Trinucleotide repeat expansion diseases |
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Definition
Huntington's - CAG
Myotonic - CTG
Fragile X - CGG
Friedreich's ataxia - GAA
Try hunting for my fried eggs(X)
May show genetic anticipation (germline expansion in females) |
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Term
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Definition
Down Syndrome (21)
Edwards' Syndrome (18)
Patau's Syndrome (13) |
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Term
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Definition
Trisomy 21 - most common chr disorder, most common cause of congenital MR
1:700
MR, flat facies, prominent epicanthal folds, simian crease, gap btw 1st and 2nd toes, duodenal atresia, congenital heart disease (most commonly septum primum -type ASD)
Increased risk of ALL and Alzheimers (>35 y.o.)
95% due to meiotic disjunction or homologous chromosomes (advance maternal age, 1:1500 women<20 to 1:25 women>45)
4% due to robertsonian translocation (chr breaks at centromere, long arms become one chr and short arms another)
1% due to Down mosaicism (no maternal association)
Pregnancy screen:
decreased alpha-fetoprotein, estriol
increased B-hCG, inhibin A
US: increased nuchal translucency
21 drinking age |
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Term
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Definition
Trisomy 18, most common trisomy resulting in live birth after downs
1:8000
severe MR, rocker bottom feet, micrognathia, low set ears, clenched hands, prominent occiput, congenital heart disease
death within 1 year of birth
18 election age |
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Term
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Definition
trisomy 13
1:15,000
severe MR, rocker-bottom feet, microphthalmia, microcephaly, cleft lip/palate, holoprosencephaly, polydactyly, congenital heart disease,
death within 1 year of birth
puberty age 13 |
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Term
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Definition
1. anaphase I - failure of paired homologous chromosomes to split (2X N+1 and 2X n-1)
2. anaphase II - failure of homologous chromosome to split at centromere (1X N+1 and 2X N and 1X n-1) |
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Term
| Robertsonian translocation |
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Definition
nonreciprocal chromosomal translocation hat commonly involves chr. pairs 13, 14, 15, 21, 22.
very common
long arms of two acrocentric chr. (centromeres near the end) fuse at centromere and 2 short arms are lost.
balanced translocations = no abnormal phenotype
unbalanced = miscarriage, stillbirth, chr. imbalance (down's pataus) |
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Term
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Definition
segment of chr. reversed end to end
may result in decreased fertility
pericentric - involves centromere, proceeds through meiosis
paracentric - does not involve centromere, does not proceed through meiosis |
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Term
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Definition
congenital microdeletion of short arm of chr. 5 (46,XX or XY, 5p-)
microcephaly, moderate to severe MR, high pitched crying/mewing, epicanthal folds, cardiac abnl. |
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Term
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Definition
congenital microdeletion of long arm of chr. 7 (deleted region includes elastin gene)
elfin facies, MR, well-developed verbal skills, cheerful, extreme friendliness with strangers, CV problems |
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Term
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Definition
variable presentation - cleft palate, abnormal facies, thymic aplasia --> T cell deficiency, Cardiac defects, hypocalcemia secondary to parathyroid aplasia
CATCH 22
microdeletion at chr. 22q11
causes aberrant development of 3rd and 4th branchial pouches
DiGeorge syndrome - thymic, parathyroid, and cardiac defects
Velocardiofacial - palate, facial, and cardiac defects |
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