Term
| What caused death in 1900s? Later into the 1990s? |
|
Definition
Pneumonia/influenza, diarrhea, enteritis, tuberculosis
Cardiovascular disease, cancer, stroke |
|
|
Term
| What caused an increase in lifespan? |
|
Definition
| Antibiotics, sanitation, vaccines, food storage improvement |
|
|
Term
| How did the diets differ between hunter gatherers and people of the agricultural movement? |
|
Definition
| Hunter gatherers mostly ate protein and fruit/nuts, agricultural societies moved into grains |
|
|
Term
| The domestication of animals resulted in many |
|
Definition
|
|
Term
|
Definition
| Terminal/interstitial deletion, insertion, inversion, reciprocal translocation |
|
|
Term
| How do you label a deletion? |
|
Definition
Del(chromosome)(band to band)
Ex. Del(X)(p11.23p22.1) |
|
|
Term
| How do you label an inversion? |
|
Definition
Inv(chromosome)(band to band)
Ex. Inv(9)(p13q22.3) |
|
|
Term
| How do you label reciprocal translocation? |
|
Definition
t(chromosome;chromosome)(band;band)
Ex. t(7;19)(q22;q13.1)
ABL-BCR translocation and IGH MYC translocation |
|
|
Term
| Prophase I chromatid phases and where does crossing over happen? |
|
Definition
Leptotene, zygotene, pachytene, diplotene, diakinesis
PACHYTENE |
|
|
Term
| What are the other viable trisomies? |
|
Definition
13-- patau syndrom
18-- edwards syndrome |
|
|
Term
| In which chromosomes do Robertsonian translocations occur? |
|
Definition
| Accrocentric-- 13-15, 21-22 |
|
|
Term
| What causes mental retardation in down syndrome? |
|
Definition
| Hippocampus, cerebellum, and prefrontal cortex are shrinked and neuronal density is decreased. Degeneration of basal forebrain cholinergic neurons (BFCNs) which synthesize ACh a neurotransmitter that is important for development and learning. |
|
|
Term
| How are down syndrome and alzheimer's interconnected? |
|
Definition
| Alzheimer patients have plaques in their brains caused by Deposition of Amyloid Beta Precursor Protein(APP), whose gene is on chromosome 21. |
|
|
Term
| What are the challenges of using mouse models for Down Syndrome? |
|
Definition
| Genes from human chromosome 21 are located on different mouse chromosomes (16, 10, 17) |
|
|
Term
| What are the mouse models for down syndrome? |
|
Definition
| Ts1Cje milder than Ts65Dn which is a translocation of chromosome 16 and 17 in mice which contain most of the genes on human chromosome 21. |
|
|
Term
| How do you assay cognitive defects in mice? |
|
Definition
| Morris Water Maze tests spatial learning and memory |
|
|
Term
| What kind of disease is Hemophilia? |
|
Definition
| X linked recessive, characterized with the inability to form blood clots |
|
|
Term
|
Definition
I: platelets attach to the endothelium
II: Platelets start to release fibrin and seal the endothelium
III: Fibrin network traps RBCs and completely seal endothel. |
|
|
Term
| How are fibrin units made? |
|
Definition
| Thrombin cleaves fibrinogen into fibrin units |
|
|
Term
| How do fibrin units generate a clot? |
|
Definition
| They polymerize using factor XIIIa |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| What is the final common pathway of coagulation? |
|
Definition
| Factor Va converts prothrombin into thrombin, which converts fibrinogen into fibrin which polymerizes units using factor XIIIa |
|
|
Term
| How are fibrin units made? |
|
Definition
| Thrombin cleaves fibrinogen into fibrin units |
|
|
Term
| How do fibrin units generate a clot? |
|
Definition
| They polymerize using factor XIIIa |
|
|
Term
|
Definition
Defect in factor IX
Aka Christmas Disease |
|
|
Term
|
Definition
|
|
Term
| What is the final common pathway of coagulation? |
|
Definition
| Factor Va converts prothrombin into thrombin, which converts fibrinogen into fibrin which polymerizes units using factor XIIIa |
|
|
Term
| What is Von Willebrand disease? |
|
Definition
| The most common coagulation disorder, low von willebrand factor. |
|
|
Term
| What is the function of the factor VIII-von willebrand factor complex |
|
Definition
| Factor VIII works with Factor IX in the coagulation cascade by activating factor X. vWF causes adhesion of platelets to subendothelial collagen, primarily through the glycoprotein Ib (GpIb) on platelets. |
|
|
Term
|
Definition
| Liver transplantation, blood transfusion, replacement of deficient factor (increased life expectancy from 1.4 years to 65 years), gene therapy. |
|
|
Term
| What are problems that come with unwanted blood clots? |
|
Definition
| Vascular thrombosis, arterial fibrilation & stroke, heart attack |
|
|
Term
| What is the bacteria for Anthrax called? |
|
Definition
|
|
Term
| What are Koch's principles? |
|
Definition
1. Microorganism must be found in abundance in all sick organisms, but none in healthy.
2. Microorganism must be isolated from diseased organism and grown in pure culture
3. Cultured microorganism must cause disease when introduced into a healthy organism
4. Microorganism must be reisolated and be identical to the original causative agent. |
|
|
Term
| What word is anthrax from? |
|
Definition
Anthrakis-- coal
For the black skin lesions on animals |
|
|
Term
| Who developed the first anthrax vaccine? |
|
Definition
|
|
Term
| Who discovered the anthrax toxins? |
|
Definition
|
|
Term
| Describe the bacteria Bacillus Anthracis |
|
Definition
| Rod shaped, gram positive, spore forming, facultative anaerobic |
|
|
Term
| What two plasmids are necessary for Anthrax infectivity? |
|
Definition
|
|
Term
| Describe the B. Anthracis capsule |
|
Definition
composed of poly-d-glutamate
synthesized by pXO2
provides protection from host phagocytes |
|
|
Term
| Which plasmid is the toxin plasmid and which toxins does it excrete? |
|
Definition
| pXO1; lethal toxin and edema toxin |
|
|
Term
| What are the three clinical forms of anthrax? |
|
Definition
| gastrointestinal, cutaneous, inhalation |
|
|
Term
| Three steps of inhalation anthrax |
|
Definition
Early-- spores are captured in lungs by pulmonary phagocytes and act as a trojan horse to infect lymph nodes
Proliferation-- spores germinate, bacteria escape and proliferate in the lymph nodes inhibiting T & B cell function
Terminal-- Proliferate in blood causing large amount of toxins leading to apoptosis and leakage of vascular endothelium |
|
|
Term
| What is the lethal factor toxin? |
|
Definition
| A zincmetallo protease, cleaves MEKs, inhibits MAPK signalling |
|
|
Term
| What is the edema factor toxin? |
|
Definition
| activates adenylyl cyclase, increases cAMP levels, prevents phagocytosis (proved through fluorescence quenching) |
|
|
Term
|
Definition
| PA, protective antigen which binds to cellular receptors |
|
|
Term
| How does the anthrax toxin enter the cell? |
|
Definition
| PA attaches to cellular receptors and cleaves furin and creates a PA heptamer complex which binds LF and EF, the entire complex is then endocytosed and fused with the endosome. |
|
|
Term
| What happens to the heptamer PA complex in the endosome for anthrax? |
|
Definition
| Acidification in the endosome lead to a conformational change in the heptamer complex changing it into a transmembrane channel, LF and EF translocate from the endosome into the cytoplasm |
|
|
Term
| How do LF and EF get from the endosome into the cytoplasm? |
|
Definition
| LF and EF lose stability in the endosome due to the low pH, their free N-terminus is drawn into the pore due to the proton gradient, a heptamer of phenylalanines is made and promotes the unfolding and movement of LF & EF, toxins move out through the pore and refold. |
|
|
Term
| EF requires what to produce cAMP? |
|
Definition
| A cellular factor that does not boil, calmodulin |
|
|
Term
| What MAPKK doesn't LF cleave? |
|
Definition
|
|
Term
| What makes anthrax a good biological weapon? |
|
Definition
|
|
Term
| Symptoms of gastrointestinal anthrax? |
|
Definition
| sore throat, nausea, diarrhea |
|
|
Term
| Symptoms of cutaneous anthrax? |
|
Definition
| Painless ulcer with black center |
|
|
Term
| Symptoms of inhalation anthrax? |
|
Definition
| flu-like symptoms, hemorrhage, vascular leakage |
|
|
Term
| Symptoms of down syndrome? |
|
Definition
Upward slant to eyes, small, flattened nose, small mouth, shortneck, small hands with short fingers,
low muscle tone, low IQ, mental retardation, if survives over 60 yrs of age, sometimes the DS patient
presents Alzheimer-like symptoms |
|
|
Term
|
Definition
|
|
Term
|
Definition
| Tissue malnutrition, not death |
|
|
Term
| What is hypertrophic cardiomyopathy? |
|
Definition
| Overgrowth in the heart muscle |
|
|
Term
| What is pathological hypertrophic cardiomyopathy? |
|
Definition
| Associated with heart attack, decrease of muscle wall size, rapid compensation of heart muscles |
|
|
Term
| What is physiological hypertrophic cardiomyopathy? |
|
Definition
| Slow growth of cells due to exercise, good!! |
|
|
Term
| How did Glembotski do his mouse experiment/model? |
|
Definition
| Tied a band around the aorta which put stress on heart and decreased blood flow, needed more blood to flow so the heart muscles grew. |
|
|
Term
| Describe the gene therapy for heart disease |
|
Definition
| HRD1 gene degrades misfolded protein and decreases heart size |
|
|
Term
| What kind of disease is cystic fibrosis? |
|
Definition
| Autosomal recessive (CFTR gene is on chromosome 7) |
|
|
Term
| Problems associated with CF? |
|
Definition
| Mucus obstructed airways and bacterial infections, blocked pancreatic ducts prevents nutrient uptake |
|
|
Term
| CF is the first disorder elucidated by |
|
Definition
|
|
Term
| A genetic map shows the order of sites derived from |
|
Definition
| Meiotic recombination frequencies |
|
|
Term
| Genetic mapping can only be conducted with |
|
Definition
|
|
Term
|
Definition
| when there are many polymorphic loci available it is possible to identify the locus of any disease related gene to a linkage region |
|
|
Term
|
Definition
| the relative distance (cM) between two loci based on the frequency of recombination |
|
|
Term
|
Definition
| records the actual distance (base pairs) between different DNA sequences |
|
|
Term
| What is the CFTR Protein? |
|
Definition
| Energy (ATP) dependent (cAMP activated) chloride channel |
|
|
Term
| Describe the development of mucus due to Cl- ions |
|
Definition
| The defective CFTR protein channel decreases secretion of Cl- ions and influxes Na+ ions. The accompanying water influx causes dehydration at the cell surface and leads to sticky mucus! |
|
|
Term
|
Definition
|
|
Term
|
Definition
| Absent protein, normal mRNA abundance |
|
|
Term
|
Definition
| Protein is made but degraded |
|
|
Term
|
Definition
| Protein is made but is nonfunctional |
|
|
Term
|
Definition
| Functional protein but less effective |
|
|
Term
|
Definition
|
|
Term
|
Definition
| Protein is unstable at cell surface |
|
|
Term
| ΔPhe508 (ΔF508) is what class mutation |
|
Definition
|
|
Term
| How and why is ΔF508 degraded? |
|
Definition
| It is folded incorrectly and translocated by ERAD to be degraded by a proteasome |
|
|
Term
|
Definition
| ER associated degradation |
|
|
Term
| What does bicarbonate (HCO3-) do for CF? |
|
Definition
| Allows decrease of viscosity of mucus by incorporation of H+ |
|
|
Term
| Only effective treatment of respiratory failure in CF is |
|
Definition
|
|
Term
|
Definition
| Bronchodilator drugs (Pulmozyme & hypertonic saline) and aminoglycosides (gentamycin/ataluren)-- terminate translation, with a low concentration you can skin stop codons |
|
|
Term
| What does ivacaftor/kalydeco do? |
|
Definition
| Targets the Glylcine551Aspartic acid (G551D) mutation by improving the transport of chloride by direct channel binding. |
|
|
Term
|
Definition
| CFTR corrector that partially restores CFTR function in people who are homozygous for F508del, supresses protein folding defects by enhancing interactions among the NBD1, TMD1, and TMD2 domains |
|
|
Term
|
Definition
| Knock out and knock in mice! |
|
|
Term
| What are the bacterial agent and the toxin of cholera? |
|
Definition
| vibrio cholerae, Cholera toxin (ctx) |
|
|
Term
| How much bacteria must be ingested to get Cholera? |
|
Definition
|
|
Term
| Cholera is also known as, + its symptoms |
|
Definition
| The blue death due to dehydration, 10-20L of water loss/day, severe diarrhea |
|
|
Term
| Treatment and prevention of Cholera |
|
Definition
TREAT: IV rehydration, Zinc, antibiotics(dox. or azithromycin)
PREVENT: sanitation, vaccination, water filter/boil |
|
|
Term
|
Definition
| Gram negative, comme shaped, motile, single polar flagellum |
|
|
Term
|
Definition
| Most pathogenic O1 E1 Tor, & O139 |
|
|
Term
| Structure of cholera toxin |
|
Definition
| 2 alpha subunits and 5 beta subunits |
|
|
Term
|
Definition
| Keeps GPCR on by losing ability to hydrolyze GTP, continuously activating AC and increasing cAMP levels which leads to chloride release and water efflux |
|
|
Term
| Agricultural societies saw a large increase in the types and frequency of infectious diseases. Name three common infectious human diseases and their domesticated animal of origin |
|
Definition
Measles;cattle, Pertusis;pigs, Smallpox;cattle,
Stomach Ulcers (Helicobacter);sheep, Tuberculosis;goats, Influenza;pigs, birds, dogs |
|
|
Term
Hemophilia A patients are insufficient in factor???while Hemophilia B patients are insufficient in
factor ??? |
|
Definition
|
|
Term
Fill in the blanks for the following statement: Bacillus anthracis is a gram __________bacteria,
which carries two plasmids _______ and ______. The capsule, encoded by one of the plasmids is
composed of _____________, providing protection from host cell phagocytosis. |
|
Definition
| Positive, PXO1 & PXO2, poly-d-glutamate |
|
|
Term
| What is the connection between Down syndrome and Alzheimer’s? |
|
Definition
Alzheimer’s patients have plaques in their brain from a gene called amyloid beta precursor
protein (APP). However, this gene is located on chromosome 21. This means that for Down
Syndrome patients, the extra chromosome 21 will make the patient more susceptible to translating
the APP gene and hence the plaques. This results in Alzheimer’s in Down Syndrome patients. |
|
|
Term
| What feature of a chromosome causes the darker stained bands on a karyotype image? |
|
Definition
| High G-C content regions. |
|
|
Term
Describe the mechanism by which Anthrax toxins enter the host cell. Is the Protective Antigen (PA)
necessary for Anthrax virulence? (ii) Is PA alone sufficient for virulence? Explain. Describe the
conformational changes PA undergoes as it facilitates toxin release. What changes do the toxins
undergo to cross the membrane? |
|
Definition
All host cells carry an Anthrax receptor (ATXR) on their cell surface. The protective antigen is normally
bond to furin. Furin is cleaved from the PA by host cell proteases creating the PA monomer. Seven PA
monomers must come together to form a heptamer. This heptamer is then bound by both the Lethal
Factor (LF) and the Edema Factor (EF), and ultimately binds ANTXR. PA along with both factors is
endocytosed into an endosome of the cell. The low pH of the endosome causes a conformational change
of PA, which allows LF and EF to enter the cytosol of the cell.
Yes PA is required for LF and EF to enter the cell. But is not suffienct for virulence alone.
PA must change from a membrane bound protein to a transmembrane pore. The two toxins must partially
unfold to cross the pore formed by PA. This all occurs in response to the low pH of the endosome. |
|
|
Term
Explain how two WT (normal phenotype-no non-disjunctions) parents produce a Down Syndrome
offspring. |
|
Definition
| ROBERTSONIAN TRANSLOCATION |
|
|
Term
What protein activates the Edema Factor (EF)? What occurs in response to EF activation by this
molecule? What host cell defense mechanism is inhibited by this process? |
|
Definition
Calmodulinïƒ EF
activationïƒ increased cAMP levelsïƒ inhibits host cell phagocytosis |
|
|
Term
| Why is karyotyping usually done in lymphocytes or in fibroblasts (skin cells)? |
|
Definition
Karyotype is the complete set of all chromosomes in a prophase with two chromotids.
Therefore, cells have to be dividing. |
|
|
Term
| Genetic risk factors of Late Onset Alzheimer's Disease |
|
Definition
| A combination of multiple risk alleles with modest and patially penetrant effects, apolipoprotein EF (ApoE4, only accounts for 10-20% of LOAD risk |
|
|
Term
| Is getting rid of beta-amyloid plaques going to cure Alzheimer's? |
|
Definition
| No, no good correlation between number of plaques and severity of memory loss, monomer of Amyloid beta peptide is harmless, but there is a good correlation between soluble levels of amyloid beta oligomers, number of peptides in these oligomers is controversial (2-12), injection of this impaired memory in rats, antibodies against AmyBeta peptides reversed memory loss in AD mouse model without reducing plaques |
|
|
Term
| Describe the pathogenesis of Alzheimer's disease |
|
Definition
| Production and self assembly of Amyloid beta toxic species initiates changes that lead to neurodegeneration, Amyloid beta proteotoxic stress triggers the hyperphosphorylation and aggregation of microtubule associated protein tau, leading to neurofibrilary tangles |
|
|
Term
| Other names for Lou Gehrig's disease |
|
Definition
| The creeping paralysis, amyotrophic lateral sclerosis |
|
|
Term
| Symptoms for Lou Gehrig's disease |
|
Definition
| Muscle weakness, problems with speech, swallowing, breathing, twitching and cramping of muscles, impairment of the use of arms and leg |
|
|
Term
| What genes are thought to cause ALS? |
|
Definition
SOD1, Cu/ZN SuperOxide Dismutase
Defects in chromosome 21
FUS/TDS, TDP-43 |
|
|
Term
|
Definition
| A gene that codes for a protein which accumulates in many neurons of ALS patients, the protein is sticky and fragments to form detergent resistant aggregates |
|
|
Term
|
Definition
| Superoxide dismutase 1-- converts superoxides which are produced by errors of oxidative phosphorylation in mitochondria, to water and hydrogen peroxide |
|
|
Term
|
Definition
| Increase uptake or clearance of glutamate from the synapse |
|
|
Term
|
Definition
| Number of possible fates open to a cell |
|
|
Term
|
Definition
| All fates of cells are available (zygote) |
|
|
Term
|
Definition
| Many fates but not all (embryonic cells) |
|
|
Term
|
Definition
|
|
Term
| Two characteristics of stem cells |
|
Definition
| They are unspecialized cells that renew themselves indefinitely through cell division, and they can be induced to become specialized cells thru differentiation |
|
|
Term
| How do you obtain embryonic stem cells? |
|
Definition
| From the inner cell mass of the embryo! |
|
|
Term
| What are the only adult stem cells that can be obtained? |
|
Definition
| Blood stem cells from the bone marrow |
|
|
Term
| How to ID blood stem cells? |
|
Definition
| Using cluster of differentiation surface markers! CD34+, CD31- |
|
|
Term
|
Definition
| Fluorescence activated cell sorter |
|
|
Term
| How are stem cells activated to proliferate? |
|
Definition
|
|
Term
| What is the moral debate regarding embryonic stem cells? |
|
Definition
| It is simply the consumption of donated embryos, is this considered a life? |
|
|
Term
| Who discovered the mature cells can be reprogrammed to become pluripotent? How? |
|
Definition
John B. Gurdon & Shinya Yamanaka, Gurdon did this through cloning by essentially taking out the frog nucleus of a frog embryo and replacing it with a tadpole nucleus, this embryo developed into a tadpole!
Yamanaka took skin cells and transferred four genes into these cells that allowed them to be reprogrammed to develop into any kind of cell. iPS cells! |
|
|
Term
| What four genes did Yamanaka transfer? |
|
Definition
|
|
Term
| What is the problem with c-Myc? |
|
Definition
| It is an oncogene, so it causes cancer (20%) |
|
|
Term
|
Definition
| The study of heritable changes in phenotype or gene expression caused by mechanisms other than changes in the DNA sequence |
|
|
Term
| Examples of epigenetic changes? |
|
Definition
| Cell differentiation (from totipotent cells to specialized cell types), X-inactivation, imprinting |
|
|
Term
| What is the principal means of imprinting? |
|
Definition
| DNA methylation of cytosine at CpG islands |
|
|
Term
| What is the histone code hypothesis? |
|
Definition
| Particular combinations of histone modifications define the conformation of chromatin--> activity of the DNA |
|
|
Term
| Enzymes involved with histone modifications on lysines |
|
Definition
| Histone acetyltransferases (HATs), histone deacetylases (HDACs), histone methyltransferases (HMTs), histone demethylases |
|
|
Term
| Histone activating modifications |
|
Definition
| H3K4me, H3K14ac, H3K14ac+H3S10P |
|
|
Term
| Histone repressive modifications |
|
Definition
| H3K9me, H2aK119ub, H3S10P+H3S28P (chromosomal condensation) |
|
|
Term
| What is prader willi syndrome? What are its symptoms? |
|
Definition
| Neurodevelopmental disorder that affects both sexes, symptoms include reduced muscle tone, lack proper suckling for milk in newborns, rapid weight gain, obesity, delayed development of motor skills, infertility due to underdeveloped sex organs, learning diabilities |
|
|
Term
| What is the basis of Prader-Willi syndrome? |
|
Definition
| The loss of functional paternal small nucleolar organizing RNA gene, SNORD116 expression, paternally imprinted |
|
|
Term
| Where is the gene that causes Prader Willi Syndrome? How does it genetically come about? |
|
Definition
| 15q11-13, deletions or a uniparental disomy of chromosome 15 lead to paternal imprinting of this locus |
|
|
Term
| What is Angelman syndrome? What are its symptoms? |
|
Definition
| Another neurodevelopmental disorder that affects both sexes. Symptoms include: severe developmental delay, mental retardation, awkward gait, tremors, seizures, protruding tongue, absence of speech, uncontrolled bursts of laughter and a happy disposition |
|
|
Term
| What missing gene leads to Angelman syndrome? What does it encode for? |
|
Definition
| maternally expressed UBE3A which encodes for ubiquitin protein ligase E3A |
|
|
Term
|
Definition
| The transmission of the gene imprint over rounds of cell division and generations in non mendelian fashion |
|
|
Term
|
Definition
| The imprinted locus can be erased and reset in the offspring depending on the gene from mother or father |
|
|
Term
| Most imprintable genes affect... |
|
Definition
| Fetal growth, nutrient transfer through the placenta, cell proliferation, and brain development |
|
|
Term
| Genomic imprinting creates a ____ condition |
|
Definition
| Hemizygous! Mutations/deletions from the non imprinted genes give disease phenotypes |
|
|
Term
| What did Gregg et al discover about gene expression by comparing mouse embryonic day 15 brain and adult brain RNA? |
|
Definition
| Parent of origin allelic effects in over 1300 loci, many imprinted genes are related to feeding and motivated behaviors, metabolism, cell adhesion; and mom's influence comes first-- maternal genes dominate in developing brains while paternal ones lead in adulthood |
|
|
Term
| Methods of X inactivation |
|
Definition
| Silencing of one X chromosome by XIST |
|
|
Term
| Characteristics of an inactivated X chromosome |
|
Definition
| Highly condensed chromatin/heterochromatin or a barr body, nuclear envelope association, late replication, lack of transcription from most of the genes, XIST RNA production |
|
|
Term
|
Definition
| A non coding RNA that associates with and initiates the activation of the X chromosome from which it is produced |
|
|
Term
| What is evidence that Xist is crucial for the initiation of X chromosome inactivation? |
|
Definition
| Transfer of a 450 kb segment containing Xist gene into male embryonic cells resulted in random inactivation of either that autosome or endogenous x chromosome |
|
|
Term
| What are the syndromes with aneuploidy in the sex chromosomes after fertilization? |
|
Definition
XO: Turner's syndrome
XYY: Super Male
XXY: Klinefelter's syndrome |
|
|
Term
| Characteristics of Klinefelter's syndrome |
|
Definition
| Nondisjunction of X chromosome in mother or father during meiosis. Males have sparse body hair, are tall, have small testes. Infertility comes from absent or low levels of sperm, development of breast tissue, mental retardation, increased risk of breast cancer, germ cell tumors, and osteoporosis |
|
|
Term
|
Definition
| Failure of normal testes development specifically endocrine Leydig cells, results in a low serum testosterone level, Leydig cells make and secrete testosterone |
|
|
Term
| Treatments for Klinefelter's |
|
Definition
| Testosterone replacement, surgery for gynecomastia (breast enlargements), psychological help |
|
|
Term
| How is it possible that a double dosage of X chromosome in Klinefelter's leads to a relatively mild phenotype? |
|
Definition
| One X chromosome remains active while the other undergoes inactivation. |
|
|
Term
|
Definition
| X inactivation allows female and male cells to contain similar levels of X encoded gene products |
|
|
Term
| Two barr bodies in one cell from someone who is phenotypically a female, what is the genotype of their sex chromosomes? |
|
Definition
|
|
Term
| Symptoms of Turner's syndrome |
|
Definition
| Kidney abnormalities, reduced life expectancy by 13 years, high incidence of congenital heart disease, enlarged lymph nodes, short stature, webbed neck, delayed sexual maturation, lack of secondary sexual characteristics, turned in elbows, broad shield like chest with widely spaced nipples |
|
|
Term
| Treatment for Turner syndrome |
|
Definition
| Growth hormone therapy, estrogen replacement |
|
|
Term
| If one X is inactivated, why are XXY or XO individuals abnormal? |
|
Definition
| About 15% of X chromosome genes escape X inactivation |
|
|
Term
| What are pseudoautosomal regions? (PARs) |
|
Definition
| Regions that are identical on X and Y chromosomes |
|
|
Term
| Genomic imprinting process |
|
Definition
| During fertilization alleles of genes from mother and father come together, genomic imprinting/mark erasing occurs at meiosis, and mark reset occurs at meiosis 2 |
|
|
Term
|
Definition
| Cell body, dendrites, and an axon |
|
|
Term
| What do Schwann's cells do? What about oligodendrocytes? |
|
Definition
| Make myelin sheath for neurons in the PNS, oligodendrocytes make myelin sheath for neurons in the CNS |
|
|
Term
| What are the functions of the myelin sheathe? |
|
Definition
| Insulate axon, increase speed of transmission of nerve impulse |
|
|
Term
| What is multiple sclerosis? |
|
Definition
| Autoimmune disease where the self immune system attacks the myelin sheath of its own CNS, the damaged myelin forms scar tissue (sclerosis) |
|
|
Term
| Symptoms of multiple sclerosis |
|
Definition
| Numbness or weakness in one or more limbs, loss or double vision, tingling or pain, electric shock sensations, tremor, fatigue, dizziness |
|
|
Term
| How do you inherit multiple sclerosis |
|
Definition
| Not directly inherited, 1/40 chance of getting it from a first degree relative, 1/4 chance of having it if your identical twin has it |
|
|
Term
| How do you treat multiple sclerosis |
|
Definition
| Interferon beta (cytokine), Glatiramer (random tetramer of 4 amino acids), cortocosteroids (reduce inflammation), muscle relaxants |
|
|
Term
| What is the treatment interferon beta for MS? |
|
Definition
| Leads to a reduction in MS disease activity, through expression of many genes, does not reverse damamge and has a flu like side effect |
|
|
Term
| Alzheimer Disease Symptoms |
|
Definition
| Loss of short term memory, no accurate sense of time, respiratory failure |
|
|
Term
| Neuropathological features of Alzheimers |
|
Definition
| Loss of synapses and neurons in brain, dense spherical structures accumulate outside of neurons (amyloid plaques), aggregation of fibrils (neurofibril tangles NFTs with in cell body and dendrites of brain) |
|
|
Term
| How is AD characterized in the brain? |
|
Definition
| By massive levels of cell death, brain shrinkage, defects early in cholinergic neurons |
|
|
Term
| What are amyloid bodies/plaque? |
|
Definition
| Visible abnormalities in AD brains, amyloid precursor protein accumulation, deposit of amyloid beta protein (AB) which is derived from a larger protein APP (amyloid precursor protein) |
|
|
Term
| What makes amyloid beta protein from APP? |
|
Definition
| Beta and gama secretase make cuts to APP to make AB40 and AB42 respectively |
|
|
Term
| What are neurofibrillary tangles (NFTs)? |
|
Definition
| Main fibrous elements of NFTs are numerous paired helical filaments (PHFs) which consists of two cross linked, intertwined protein strands with each strand making up a number of joined tau protein molecules that make a tau filament which binds to tubulin which facilitates the making of microtubules. Tau maintains stability of microtubules. Microtubules are important for vesicle transport up and down the axons |
|
|
Term
|
Definition
| Only 10% of cases occur as autosomal dominant inheritance, onset is 55-60 years which is early onset AD (EOAD), 90% of cases are late onset (LOAD>65 yrs), but 25-40% of LOAD cases have a close relative with AD indicating a possible genetic component or environmental factor |
|
|
Term
| What evidence is there to show that amyloid deposits are involved with AD? |
|
Definition
| Excess APP are found in down syndrome patients who are at high risk for EOAD, missense mutation\s that result in altered cleavage activity of APP by proteins encoded by presenilin 1 or 2 are also associated |
|
|
Term
|
Definition
| PSEN1 mutations accound for 40% of EOAD and PSEN2 was also identified, PSEN1 &2 are components of gamma secretase |
|
|
Term
| Which AB is more likely to form plaques in the brain? |
|
Definition
| AB42, presenilin mutations lead to an increase in the ratio of AB42 to AB40 |
|
|
Term
| Genetic risk factors of LOAD |
|
Definition
| Apolipoprotein E4 (ApoE4) is one of the only confirmed risk factors for LOAD (10-20%) |
|
|
Term
| What is the amyloid hypothesis? |
|
Definition
| Production and self assembly of AB toxic species and stress triggers the hyperphosphorylation and aggregation of the microtubule associated protein tau leading to neurofibrillary tangles. |
|
|
Term
| Is getting rid of beta amyloid plaques going to cure AD? |
|
Definition
| No good correlation between number of plaques and severity of memory loss, monomer of AB peptide is harmless, injection of AB into rats impaired their memory |
|
|
Term
| How does APP promote neuronal cell death? |
|
Definition
| Trophic factor deprivation triggers cleavage of surface APP by B secretase to release N APP which binds death receptor 6 (DR6) to trigger degeneration through caspase 6 in axons and caspase 3 in cell bodies |
|
|
Term
| What is Parkinson's disease? |
|
Definition
| The second most common neurodegenerative disorder, mean age of onset is 60 |
|
|
Term
|
Definition
| Tremor, rigidity, Bradykinesia, postural instability, difficulty walking talking or other simple tasks |
|
|
Term
|
Definition
| Signals that control body movements travel along neurons that project from the substantia nigra to striatum. These "nigro-striatal" neurons release dopamine (a neurotransmitter) to striatum. In Parkinson's patients, dopaminergic neurons (melanin high) in the nigro-striatal pathway degenerate for unknown reasons. Dopaminergic neurons are lost in the substantia nigra and lewy bodies are present in the remaining neurons |
|
|
Term
|
Definition
| Abnormal aggregates of protein inside nerve cells, major component being alpha-synuclein |
|
|
Term
| What is a single nucleotide polymorphism? |
|
Definition
| SNP-- a single base pair difference at a specific location, 1 SNP every 300bp, useful as genetic markers |
|
|
Term
| What is a single nucleotide variant? |
|
Definition
| A difference in DNA sequence at a single position in the genome, each variant may represent either an inherited or aquired change |
|
|
Term
| What is a genome wide association study? |
|
Definition
| An examination of many common genetic variants in different individuals to see if any variant is associated with a trait. GWAS focuses on associations between SNPs and traits like major diseases |
|
|
Term
| What is the common disease-common variant hypothesis? |
|
Definition
| Common heritable diseases are caused by many common alleles. All of them are with weak effect but act together to make the disease phenotype |
|
|
Term
|
Definition
| PTEN-induced putative kinase 1, which contains a mitochondrial targeting sequence and a putative transmembrane region that directs kinase domain to surface of mitochondria. It is a serine threonine kinase. PINK1 deficiency leads to shortening, swelling, and fragmentation of mitochondria |
|
|
Term
|
Definition
| Parkin is structured with a ubiquitin like domain at N terminus, followed by 3 ring finger domains, separated by and in between ring domain, each which bind two Zn2+ atoms. It is a E3 ubiqutin protein ligase |
|
|
Term
|
Definition
| PINK1 is imported into the IMM and cleaved by mito. processing protease and degraded. PINK1 remains on OMM and its autophosphorylation allows association with Parkin, which ubiquitinates OMM substrates |
|
|
Term
|
Definition
| Genes associated with dominant lewy body diseases, alpha-synuclein is inherently prone to misfold and aggregate |
|
|
Term
|
Definition
| No cure. Levodopa is a precursor of neurotransmitter dopamine. Carbidopa is an inhbitor of dopemine decarboxylase, DDC. It delays conversion of levodopa into dopamine until it reaches the brain. |
|
|
Term
| Where is HD found on the chromosome? |
|
Definition
|
|
Term
| What is huntingtons disease? |
|
Definition
| The huntingtin gene has an uninterrupted stretch of CAG/GTC repeats in first exon. People without the disease have 6-35 repeats, HD patients have 40+ repeats |
|
|
Term
|
Definition
| Unstable due to unequal recombination and replication slippage |
|
|
Term
|
Definition
|
|
Term
| Huntington's Disease is also known as... |
|
Definition
| PolyQ disease, trinucleotide repeat expansion disease (TRED) |
|
|
Term
| What accounts for anticipation/worsening of disease phenotype as huntingtons gene is transmitted thru generations? |
|
Definition
| Intergenerational repeat expansion |
|
|
Term
|
Definition
| Worsening of disease phenotype in successive generations |
|
|
Term
| What is the polymerase slippage model? |
|
Definition
| During replication polymerase slippage and subsequent reattachment may cause a bubble to form in new strand. Slippage is thought to occur in sections of DNA with repeated patterns of bases. DNA repair mechanisms then realign the template strand with new strand and bubble is straightened out |
|
|
Term
| What is likely involved during DNA synthesis of the expansion of a trinucleotide repeat? |
|
Definition
|
|
Term
| How does the CAG repeat expansion lead to neurodegeneration? |
|
Definition
| Misfolding of expanded polyglutamine tracts, aggregation and nuclear inclusions, when length exceeds ~35 the polyglutamine tract adopts abnormal conformation |
|
|
Term
| How to study the nature of proteins? |
|
Definition
| Using GFP as a reporter protein to test tissue specific activity of a promoter, or to test how a gene is expressed during development, or to fuse to another protein to make a chimeric functional protein |
|
|
Term
|
Definition
| Transmissibile spongiform encephalopathies, rare forms of progressive neurodegenerative disorders that affect humans and animals |
|
|
Term
| What are spongiform changes in the brain? |
|
Definition
| Brain vacuolation, astrogliosis, neuronal apoptosis, accumulation of misfolded prion plaques |
|
|
Term
| Why did people think Mad Cow disease was caused by slow viruses? |
|
Definition
| Because of the long incubation time between time of infection and appearance of disease |
|
|
Term
|
Definition
| Creutzfeldt-Jakob disease (CDJ), Mad Cow Disease |
|
|
Term
|
Definition
| A disease originated in Papua New Guinea known as the Laughing Death and means to shake or shiver |
|
|
Term
|
Definition
Ambulatory, sedentary, and terminal
PRIMARY CEREBELLAR SYMPTOMS |
|
|
Term
| Ambulatory stage symptoms |
|
Definition
| Myoclonus, unsteadiness of stance/gait/hands/eyes, dysarthria, slurring of speech, tremor, uncoordination of lower extremities |
|
|
Term
|
Definition
| Can't walk, severe tremors, ataxia, shock-like muscle jerks, emotional lability, inappropriate laughter, extreme depression, cognitive decline |
|
|
Term
| Intensifying symptoms, urinary and fecal incontinence, difficulty swallowing (dysphagia), lapse into coma, lose control of breathing |
|
Definition
|
|
Term
| Who is Carleton Gajdusek? |
|
Definition
| MD, genius, knew about cannibalism, had all similar information as us, ruled out Kuru as an infectious agent, convinced it was genetically caused and tried to publish but was denied |
|
|
Term
|
Definition
| He studied Scrapie, a disease exclusive to sheep and goats with symptoms similar to Kuru with no inflammation, transmissible to goats & sheep but agent is unknown and unusual |
|
|
Term
| Three strange things about Kuru and Scrapie |
|
Definition
| 100% fatal, cause no immune response, have long incubation times |
|
|
Term
|
Definition
| Scientist think it is a camouflaged virus, hiding in a coat of host protein and is extraordinarily resilient (survived boiling, freezing, formaldehyde, carboxylic acid, chloroform, desiccation, UV exposure) |
|
|
Term
| Describe the size of the Scrapie agent |
|
Definition
| Passes through fine filters and stays in solution despite ultracentrifugation, if it had a genome it would be 1000x smaller than smallest known virus |
|
|
Term
| What did JS Griffith propose in 1967? |
|
Definition
| Scrapie agent is a protein that turns on its own transcription, it is a variant protein form that can corrupt the native form of protein to its state by oligomerization, and it is an antibody that stimulates its own production |
|
|
Term
| What is animal rendering? |
|
Definition
| Practice of processing animal byproducts into commercial material as animal feed |
|
|
Term
| Describe the progression of Bovine Spongiform Encephalopathy |
|
Definition
| First case was found in a cow that was fed livestock feed from a sheep that died of scrapie (1986), Dr. Richard Lacey says scrapie and BSE are same disease, infected over 100k cows in europe in the 1990s |
|
|
Term
|
Definition
France: 160 cases in 2000
Germany: 20 cases in 2001
UK: 1277 cases in 2000 |
|
|
Term
|
Definition
| Creutzfeldt Jakob disease, found in UK, linked with consumption of BSE contaminated beef, shares symptoms with classic CJD but median age of death is 28 |
|
|
Term
| Who is Stanley Pruisner and what did he do? |
|
Definition
| Isolated a brain protein called PrP(Prion Protein) which has two forms, normal (c) and abnormal (sc), found that abnormal form tracked with infectivity |
|
|
Term
|
Definition
| Proteins that can take on more than one 3D structure |
|
|
Term
|
Definition
| Has the ability to convert PrPc to sc, chain reaction resulting in a cluster of tangled nonfuctional proteins called plaques which are aggregates of PrPsc in brain, it is resistant to any form of digestion and resistant to high temps and disinfectants, body removes these plaques leaving holes behind |
|
|
Term
| What are some molecular prion characteristics |
|
Definition
| Rich in polar amino acids, like glutamine or asparagine, poor secondary structure preference, domain is dispensable for function, protein can exist in soluble or aggregated form |
|
|
Term
| Symptoms of BSE in cattle |
|
Definition
| Progressive degeneration of nervous system, changes in temperament (nervousness, aggression, abnormal posture, incoordination), decreased milk production, loss of body weight |
|
|
Term
|
Definition
| Postmortem analysis of brain tissue (vacuolation of neurons and perivascular fibrils of amyloid through immunostaining, and astrocyte infilteration) or by detection of abnormal form of prion protein |
|
|
Term
|
Definition
| Sheep with scrapie used in Meat and Bone Meal (MBM) aka Offal is fed to cattle and infected beef is eaten by humans. Other ways include dura and corneal transplants, being operated on with surgical tools use on a CJD patient, or EEG depth probes contaminated by prior patients |
|
|
Term
|
Definition
| Don't feed cattle animal byproducts, vaccinate cattle, meat inspection, US will not import cattle from Britain |
|
|
Term
| Other names of Lou Gehrig's Disease |
|
Definition
| ALS, Motor Neuron Disease (Jean Martin Charcot), creeping paralysis, amytrophic lateral sclerosis |
|
|
Term
|
Definition
| Muscle weakness, twitching and cramping of muscles, impairment of use of limbs, speech breathing and swallowing difficulty |
|
|
Term
| What causes of ALS are genetic? |
|
Definition
| SOD1, Cu/Zn superoxide dismutase, defects in chromosome 21, FUS/TDS, TDP43 |
|
|
Term
| Why do motor neurons degenerate? |
|
Definition
| TDP43 protein accumulates in cell bodies of motor neurons and cortical neurons, it fragments and is sticky and forms detergent resistant aggregates, as well as FUS aggregates due to FUS mutations |
|
|
Term
|
Definition
Superoxide Dismutase 1, misfolded proteins accumulate in ER causing stress due to a mutant SOD1 leading to ASK1 activation and cell death
Converts superoxide to water and hydrogen peroxide |
|
|
Term
|
Definition
|
|
Term
|
Definition
| Many fates but not all are available |
|
|
Term
|
Definition
| Cmon nigga u kno dis one at least |
|
|
Term
| Characteristics of stem cells |
|
Definition
| Cells of variable potency, unspecialized, renew indefinitely thru cell division, can be induced to become specialized cells |
|
|
Term
| What are embryonic stem cells |
|
Definition
| Cells from the inner cell mass of embryo, easy to get |
|
|
Term
| What are adult stem cells |
|
Definition
| Aka somatic/tissue stem cells, relatively undifferentiated cells in a differentiated tissue that can renew themselves and differentiate, difficult to get (eg. neuronal stem cells from brain) |
|
|
Term
| Where are blood stem cells obtained? |
|
Definition
|
|
Term
| How do you find blood stem cells? |
|
Definition
| Make monoclonal antibodies with these bone marrow cells and ID specific cell surface proteins using cluster of differentiation (CD) |
|
|
Term
| What are blood stem cell surface markers? |
|
Definition
|
|
Term
| How do you demonstrate the existence of blood stem cells? |
|
Definition
| Irradiate mouse, inject stem cells from brown mouse, and mouse survives! |
|
|
Term
| What stage are stem cells kept in? How are they activated? |
|
Definition
|
|
Term
| Describe the process of SCNT |
|
Definition
| Cells from adult tissue containing genome to be cloned are put into an unfertilized egg whose nucleus was removed, the cells divide in the embryo and are either transferred to a culture dish or placed in a foster mother |
|
|
Term
| What is the dispute on the moral treatment of embryos |
|
Definition
| Are the means of using donated embryos permissible??? are embryos allowed to be classified as people? ESC research is hoped to achieve the relief of human suffering that is not in dispute |
|
|
Term
| What did John B. Gurdon and Shinya Yamanake get the nobel prize for? |
|
Definition
| The discovery that mature cells can be reprogrammed to become plurpotent |
|
|
Term
| What did John B Gurdon do? |
|
Definition
| Eliminate the nucleus of a frog embryo and replaced it with nucleus from a specialized cell taken from tadpole, embryo developed into a normal tadpole |
|
|
Term
| What did Shinya Yamanaka do? |
|
Definition
| Studied genes important for stem cell function by transferring 4 genes into cells taken from skin, they were reprogrammed into pluripotent stem cells that could develop into all cell types of an adult mouse called IPSCs |
|
|
Term
| What are the four genes that Yamanake injected? |
|
Definition
| Oct4, Sox2, Klf4, c-Myc -- all transcription factors |
|
|
Term
| What is the good news for iPSCs? |
|
Definition
| Give potential to bypass both practical and ethical concerns with SCNT |
|
|
Term
| What is the bad news for IPSCs? |
|
Definition
| one gene, c-Myc, is oncogenic, 20% of mice developed cancer, it is known that you can make iPSCs without c-Myc but it takes longer |
|
|
Term
|
Definition
| Increases uptake or clearance of glutamate from the synapse |
|
|
Term
|
Definition
| A malignant and invasive growth of tumor, a loss of control of cell proliferation or apoptosis that leads to the formation of a mass of cells (tumor) |
|
|
Term
| 20% of all cancers have _____, 90% have_____ |
|
Definition
| germline mutations, somatic mutation |
|
|
Term
| What is clonal evolution? |
|
Definition
| A tumor develops through repeated rounds of mutation and proliferation giving rise to a clone of fully malignant cancer cells |
|
|
Term
| What are critical cancer genes? |
|
Definition
| All genes whose mutation or abnormal expression cause cancer like oncogenes and tumor suppressor genes |
|
|
Term
|
Definition
| Expression turns normal growth into cancer |
|
|
Term
|
Definition
| Expression prevents cancer development |
|
|
Term
| How were oncogenes identified? |
|
Definition
1. Human leukemias with chromosome translocations
2. retrovirus induced cancers in animals |
|
|
Term
|
Definition
| HER2 (Human EGF Receptor 2) and Signaling cascade RTK (Receptor tyrosine kinase)-- EGF binding activates tyrosine kinase, but as an oncogene tyrosine kinase is constantly active |
|
|
Term
|
Definition
| A monoclonal antibody that attaches to a HER2+ cancel cell and can tell your bodies defense system to target it, can stop it from proliferating |
|
|
Term
|
Definition
| Receptors are dimerized and activated without ligands, gene for RTK ligand is activated constitutively in autocrine fashion |
|
|
Term
| In 20% of colorectal cancers there is activation of... |
|
Definition
| The ras raf mek erk MAP kinase cascade |
|
|
Term
| Many intracellular signaling proteins function as... |
|
Definition
| molecular switches activated by phosphorylation |
|
|
Term
| What is the philadelphia chromosome? |
|
Definition
| BCR-ABL translocation product of chromosomes 9 & 22 that leads to leukemia |
|
|
Term
|
Definition
| Blocks BCR-ABL binding stopping leukemia |
|
|
Term
|
Definition
|
|
Term
| What are tumor suppressor genes? |
|
Definition
| Genes that protect cells from becoming cancerous, constrain uncontrolled cell proliferation such as Rb and P53, repair DNA damage (BRCA1), tell cell to die (p53) |
|
|
Term
| What is Knudsen's two hit hypothesis? |
|
Definition
| A tumor suppressor gene may become nonfunctional only when both alleles are inactivated |
|
|
Term
| What is the Loss of Heterzygosity? |
|
Definition
| Loss of the expression of one allele, the loss of expression of the wild type/good allele of a tumor suppressor gene when the other is already mutated/deleted |
|
|
Term
| Six ways of losing remaining good copy of a tumor suppressor gene |
|
Definition
| Nondisjunction, gene conversion, deletion, point mutation, mitotic recombination, chromosome loss then duplication |
|
|
Term
|
Definition
| An inhibitor of DNA methytransferases that promotes DNA hypomethylation |
|
|
Term
| Mechanism once cells are given signals to grow |
|
Definition
| Mitogens activate Ras and kinase to make more Myc that promotes transcription of cyclin D which activates G1 specific Cyclin dependent kinase |
|
|
Term
| Who keeps cells from dividing? |
|
Definition
| Rb inhibits E2F, G1Cdk phosphorylates Rb and frees E2F |
|
|
Term
|
Definition
| TF that binds to DNA sequence in the promoters of many genes that encode proteins required for S phase entry to activate proliferation |
|
|
Term
| What does the loss of p53 or Rb do? |
|
Definition
| HPV! Human papillomaviruses |
|
|
Term
|
Definition
| Viruses that infect mucous membrane and skin, cause warts or cancer, HPV integrates into genome and can be detected by a pap smear (papnicolau test) |
|
|
Term
| How does HPV activate cell proliferation? |
|
Definition
| Using E6 & E7 proteins which bind to p53 and Rb respectively |
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|
