Seabury 3
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| constitutive | a gene that is on all the time and thus does not respond much to the environment
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| inducible | enzymes are produced only if substrate is present (e.g. lac)
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| repressing | if the substrate exists, no need to produce the enzyme (e.g. tryptophan)
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| negative control | gene expression (GE) occurs unless regulator molecule shuts it off
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| positive control | GE occurs only if regulator directly stimulates it (CAP/cAMP in lac operon)
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| I+ gene in lac operon | needed for lock-and-key fit of repressor and operator; if bacteria is I-, lac genes will undergo transcription/translation WITHOUT lactose
constitutive
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| O+ gene in lac operon | affects repressor chape; if gene is mutated (Oc), then no lock-and-key fit --> makes enzymes w/o lactose
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| I^s mutation in lac operon | causes the inducer to lack lactose binding site --> doesn't make enzymes
repressed
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| effect of glucose on lac operon | represses lac operon by CAP-cAMP complex binding at promoter
inducible condition
cAMP exerts positive control
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| tryptophan operon | attenuator
biosynthesis
when trp absent, the cell needs to make it
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| cellular localization pattern | where the protein goes after it is produced
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| Dscam gene | encodes protein that giudes axon growth, uses alt. splicing
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| types of regulatory RNA | short RNA
RNA interference, RNAi (animals)
post transcriptional gene silencing, PTGS (plants)
short interfering RNA, siRNA (plants)
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| short RNA | regulates CYTOPLASMIC gene expression by repressing translation or degrading mRNA
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| post transcriptional gene silencing (PTGS, plants) | dsRNA is cut every 21 nucleotides by DICER to make short interfering RNA (siRNA), which unwinds to sense and antisense strands; the antisense strand combines with a protein coplex (RISC), which recognizes, binds, and cleaves mRNA
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| microRNA | ssRNA that binds w/ internal or 3' untranslated mRNA and either
-blocks translation
-targets RNA for degradation
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| cyclin | a protein that checks conformation before cell enters next phase of cell cycle
cyclin B must be bound to CDK1 for mitosis to continue
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| G1/S | CDK4-cyclin D
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| G2/M | CDK1-cyclin B
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| tumor suppressor genes | halt passage through cell cycle
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| proto-oncogenes | promote cell division
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| RB1 | retinoblastoma
85% of those born with mutation get it (fam)
55-60% who develop mutation -> tumor (sporadic)
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| TF, EF2 | normally tell cell to stop, but in mutated form, cell cycle always on -->retinoblastoma
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| WT1 | Wilms tumor gene
kidney cancer, child
gene on HSA11p encodes TF
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| p53 | tumor suppressor gene
TF for 20 genes
normal action shut down by carcinogens
negatively regulated by MDM2
Li-Fraumeni disease
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| BRCA1-HSA17 | predisposition inherited as a dominant trait
85% w/ one mutation develop another
increased risk of breast and ovarian cancer
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| BRCA2-HSA13 | autosomal dominant
breast cancer ONLY
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| Rous sarcoma | 1st oncovirus described
SRC gene encodes for tyrosine kinase
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| Ras proteins | signal transduction proteins that reg. cell growth/division; transmit extracellular signals to cytoplasm
single aa substitution to -> mutation
30% of cancers have mutation
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| HRAS | on chromosome 11
regulates cell division in response to growth factor
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| NRAS | chromosome 1
control of cell growth
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| Philadelphia chromosome | result of reciprocal translocation between 9&22
Chronic Myelogenous Leukemia
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| metalloproteins | encode matrix cutting enzymes for metastasis to occur
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| colon cancer | -benign->malignant (95%)
-familial
1.Familial adenomatous polyposis
2.Hereditary non-polyposis colorectal cancer
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| Familial adenomatous polyposis | related genes: FAP, APC, HSA5
slow progression, rapid initiation
many polyps
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| Hereditary non-polyposis coleorectal cancer | related genes:HSA2, HSA3, MSH6, MLH3
slow initiation, rapid progression
few polyps
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| top cancer killers, men and women | men: lung, prostate, colon/rectum
women: lung, breast, colon/rectum
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| solid tumors | derived from epithelium
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| requirements for good vector | -independently replicate
-restriction enzyme cleavage site
-selectable marker (antibiotic resistance, lac)
-easy to recover
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| pUC18 | commonly used plasmid vector
has polylinker site, lac Z gene as selectable marker for blue-white screening
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| BACs | Bacterial artificial chromosome
200Kb
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| YACs | yeast artificial chromosome
230-1900Kb
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| Southern blotting | allows us to determine which DNA clones contain the DNA fragment of interest
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| roche 454 pyrosequencing | relies on detection of phosphate release during nucleotide incorporation
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| categories of genomics | -structural
-functional
-comparative
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| shot-gun sequencing | isolate genome->fragment by sonication->clone fragments into vectors->prepare clone library->clones selected at random and sequenced
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| c-value paradox | genome size (in eukaryotes) does NOT correlate with genome complexity (polyploidic plants)
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| human genome | first discovered by Venter (2007)
50% transposable elements (LINEs, SINEs)
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| chimp vs. us | differences:
-indels
-regulation of gene expression
-recombination hot spots
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| paralogs | arise from single gene duplication in SAME spp
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| orthologs | homologous genes in DIFFERENT spp
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| alpha and betablobin | sequances are similar, reflecting some common elolutionary history
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| HSA 14 | heavy chains
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| HSA2, HSA22 | light chains
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| break-nibble-add mechanism | joining of V (variable region) and J (joining region) is imprecise, subject to adding or removing a few bases (rearranging the gene)
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| proteomic tech | -2D electrophoresis: separate by charge then MW
-mass spec
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| FGF-10 | component of signal pathway controlling outgrowth in turtles
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| development, basic | 1. maternal effect genes establish gradient
2. gap genes, pair-rule genes, and segment polarity genes divide organism into segments (determination)
3. homeotic/selector genes specify the identity of each segment (differentiation)
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| runx2 | pair-rule gene
mutation in this causes 'runt', cleidocranial dysplasia
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| HOMEOBOX | shared sequence of selector/homeotic genes among many spp.
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| things that activate responsible hox genes | -retinoic acid
-fibroblast growth factors
-Wnt proteins
-bone morphogenic proteins (deer antler)
-hedgehog proteins
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| HOX-D13, HSA2q | cause synpolydactyly in humans
autosomal dominant
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| HOX-A13 | autosomal imcomplete dominance
frameshift
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| PAX | paired box genes
nervous system
mutations -> cancer, 'splotch', Waardenburg syndrome (autodom)
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| ced 3, 4, 9, 1 bcl2 | cell death genes
3&4 -> cell death in many ways
9 -> protects cell from destruction
1 -> activates 9
bcl2 -> prevents apoptosis (cancer causing gene)
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