Term
| Direction of DNA Polymerase and repair mechanism |
|
Definition
-Goes from 5'-3', the 3' end grows
-Polymerase has a 3'-5' exonuclease activity that can proofread |
|
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Term
|
Definition
-Provides an RNA template for extending the ends of chromosomes
-Has a bunch of TTAGGG sequences |
|
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Term
|
Definition
-De-amination: T-->U by losing an amine group
-De-purination: a purine is cleaved off by hydrolysis
-Thymine dimers: UV causes thymines to link up. |
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Term
|
Definition
| -When RNA Pol starts out it makes a short sequence and then aborts the transcription unless the sigma subunit is released. |
|
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Term
| RNA Polymerases in Eukaryotes |
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Definition
Pol I: Makes rRNA
Pol II: Makes mRNA
Pol III: Makes rRNA and tRNA |
|
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Term
|
Definition
small nuclear ribonuclearprotein particles used for splices.
(SNERPS) |
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Term
|
Definition
|
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Term
|
Definition
-Continuous strands of aa that fold independently from the rest of the protein.
-All proteins may be made up of about 2000 domains. |
|
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Term
| 3 Cell cycle check points |
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Definition
G1: Environment check
G2: Is DNA replicated and repaired?
Mitosis: Are chromosomes attached to the mitotic spindle? |
|
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Term
| 6 aspects of cell cycle control |
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Definition
1- must be a timer
2- must ensure order
3- must ensure each part happens once
4- must trigger complete/irreversible events
5- must have redundancies
6- can adapt for cell types and conditions |
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Term
| Chromosome types and distinguishing features |
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Definition
-Metacentric: central centromere
-Submetacentric: off-center centromere with arms of two lengths
-Acrocentric: centromere is at one end, one end has stalks with satellites for making rRNA. |
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Term
|
Definition
-Males have a lower threshold for the disease
-That's why if a female presents with the disease that it has a higher recurrence risk. |
|
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Term
| Examples of things that cause proteins to mis-fold: |
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Definition
| mutations, oxidative stress, infection, aging, cancer. |
|
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Term
| How chaperone proteins work: |
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Definition
-They clamp onto a protein and hydrolyze ATP
-Clamped conformation has an affinity for the protein
-There are chaperones in the cytoplasm, ER, and mitochondria. |
|
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Term
| How Rb and E2F work as a checkpoint |
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Definition
-E2F is a transcription factor inhibited by Rb.
-When cyclin D/ CDK 4/6 detect favorable conditions in the ECM, they phosph Rb and Rb no longer inhbits E2F.
-E2F then transcribes cyclin S and S phase is initiated. |
|
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Term
| How S-Cyclins initiate replication |
|
Definition
- S-Cyclins phosph CDC6
- CDC6 activates the ORC site and assembles MDM proteins
- The ORC site assembles replication machinery and MDM proteins act as helicases
- CDC6 and MDM proteins are deactivated until the end of mitosis, this prevents re-replication of DNA |
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Term
| Independent Segregation vs. Independent Assortment |
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Definition
Segregation: Only one allele gets passed on
Assortment: the combination of alleles passed on is random |
|
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Term
|
Definition
| Can't see on a chromosome study, but mulitple genes are affected. |
|
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Term
Missense mutation
Nonesense mutation |
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Definition
Missense: a single base changes and causes a new AA to be put in
Nonesense: a single base is changed that causes an early stop codon. |
|
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Term
| Multifactorial trait characteristics |
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Definition
- Qualitative (present or not) or quantitative (degree)
- Multiple genes and/or multiple environmental factors |
|
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Term
| Multifactorial trait relative risk |
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Definition
| prevalence among relatives/ prevalence in population |
|
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Term
| Numerical chromosomes abnormalities |
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Definition
Euploid: exact multiple of haploid set, i.e. triploidy (3n)
Aneuploid: loss or gain of whole chromosome, i.e. trosomy 21 |
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Term
| Penetrance vs. Expressivity |
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Definition
Penetrance: proportion of people with the gene that express the trait
Expressivity: the severity of a trait |
|
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Term
|
Definition
-Only happens between 2 of the sister chromatids
- Happens more in females
- decreases near centromer, increases near telomere (more so in males) |
|
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Term
| Restriction point and terminal differentiation |
|
Definition
Restriction point: go or no go, last check before S phase
Terminal differentiation: a cell can't get back into the cell cycle, i.e. RBC |
|
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Term
| Robertsonian Translocation |
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Definition
Translocation between two acrosomic chromosomes. They are balanced, and it isn't a big deal that some of the satellite dna is lost.
-Results in 25 chromosomes |
|
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Term
Self-spreading of amyloids
What are they called? |
|
Definition
-Amyloids can spread simply by seeding and providing a surface for further aggregation.
-These are called prions |
|
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Term
| The big control of the cell cycle is: |
|
Definition
CDK- cyclin dependent kinases
Different cyclins are made in each step of the cycle to move things forward
CDK-cyclin complexes are also controlled by phosph/dephosph |
|
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Term
| Unfolded Protein Response |
|
Definition
-Happens in the ER when unfolded proteins build up
-Can tell the cell to pause what it's doing or make more ER
-If there's too much bogus protein then it can tell the cell to self-destruct |
|
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Term
| What happens if too many misfolded proteins are around? |
|
Definition
-They will aggregate and form amyloids, which lead to aggresomes.
-Aggregates are cleared by autophagy or the ubiquitin system (JUNQs and IPODS) |
|
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Term
| What does it mean if a disease has a concordance of 100% among MZ twins and a rate of 25% among DZ twins? |
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Definition
| -The disease is due to a recessive trait. |
|
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Term
| What does an LOD score of 0 mean? |
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Definition
| It means that the two loci are on top of each other (extremely close) |
|
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Term
|
Definition
| Means that two loci are very close to each other. |
|
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Term
| Tay-Sachs Disease: mode of inheritance, defect, classic symptoms |
|
Definition
MOI: autosomal recessive
Defect: lack of hexosaminadas activity, build up of GM2
Symptoms: mental/physical deterioration as gangliosides build up in neurons, decrease vision
-Similar to Sandhoff, which lacks A&B |
|
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Term
|
Definition
Autosomal Recessive
-horizontal inheritance |
|
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Term
|
Definition
X-linked
-only males across many generations, all connected through females. |
|
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Term
|
Definition
-lack of certain enzymes in the lysosome to break down mucopolysaccharies (GAGs)
I-Hurlers (AR)
II-Hunter (X-linked)
-severe CNS and skeletal
-can be cross correcting because of allelic heterogeneity |
|
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Term
| Allelic heterogeneity vs. locus heterogeneity |
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Definition
Allelic: different mutations at the same locus, mutation at one place that causes different phenotypes
Locus: mutations at different loci, different loci producing similar phenotypes |
|
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Term
| Glycogen storage diseases |
|
Definition
-Deficiency in glucose and accumulates glycogen
-Example is von Gierke's disease, can't convert G6P
-Controlled by diet manipulation |
|
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Term
| What's the disease that results in a build up of propionyl-CoA? |
|
Definition
Propionic acidemia
-Results in propionyl-CoA being converted into a bunch of different acids.
-Treated w/bicarb and protein restriction |
|
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Term
|
Definition
Multiple Carboxylase Deficiency
-Lack of certain apocarboxylases in the biotin cycle
-Results in lack of the product biotin
-Can be treated well w/biotin supplementation |
|
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Term
|
Definition
-Mutation results in protein has little or no function and the normal protein can't produce activity at high enough levels
-example is familial hypercholesterolemia, too few LDL receptors |
|
|
Term
|
Definition
-Mutation results in a protein that competes with the normal protein function
-Insulin Chicago: mutated insulin binds to the receptor but doesn't have any activity
-Also dimeric binding/inhibition |
|
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Term
|
Definition
| A dominant negative mutation might decrease the stability of multimeric proteins -Example is osteogenesis imperfecta- brittle bones -defects in collagen decrease stable triple helices, blue sclera |
|
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Term
| Achondroplasia vs. Wolf Hirschhorn Syndrome |
|
Definition
-Achondroplasia results from a point mutation that results in a gain of function for the FGFR3 gene.
-WHS results from a deletion of the FGFR3 gene
-These two have different effects: WHS has growth def w/normal limb proportions and severe mental retardation. Achond has short stature, shortened limbs, and normal intelligence. |
|
|
Term
| Familial male precocious puberty |
|
Definition
-Autosomal dominant, sex-limited inheritance
-Results in an over active LH receptor that initiates testosterone synthesis and early puberty. |
|
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Term
|
Definition
| -Autosomal dominant, long limbs/fingers -Caused by a mutation in the Fibrillin-1 gene, affects connective tissue -Patients often die from cardiac difficulties |
|
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Term
|
Definition
-Pretty common, autosomal dominant
-Cafe-au-lait, neurofibromas, lower IQ
-NF1 gene is very large and has a high mutation rate.
-NF1 codes for neurofibromin which is a tumor suppressor |
|
|
Term
|
Definition
Patau Syndrome
-Holoprosencephaly, severe mental deficiency,
- 82% mortality in the first year |
|
|
Term
|
Definition
-Edwards syndrome
-Clenched hand with overlapping fingers, prominent occiput, severe retardation
- 90% mortality by 12 months |
|
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Term
|
Definition
| -Monosmy X, short stature, webbed neck, infertile, lower IQ, |
|
|
Term
|
Definition
-Most common cause of mental retardation
-Children have a normal phenotype, adults have long face, and big testes.
-Frequency increases w/each subsequent generation b/c of trinucleotide expansion in females. |
|
|
Term
| How FMR-1 works in fragile X |
|
Definition
If CpG is overmethylated then it decreases transcription of FMR-1.
-Over methylation of CpG also leads to an increase in the number of trinucleotide repeats |
|
|
Term
|
Definition
The appearance of a genetic trait at an earlier age or with
greater severity in successive generations. |
|
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Term
|
Definition
-Autosomal dominant w/trinucleotide repeats in the non-coding region
-weakness and difficulty relaxing muscles
-affected children are only born from affected mothers, not affected fathers. |
|
|
Term
|
Definition
Spinal and bulbar muscular atrophy - Kennedy Disease
-loss of spinal cord bulbar motor neurons - weakness
-gynecomastia, reduced fertility,
-trinucleotide in a coding region, expansion occurs paternally |
|
|
Term
|
Definition
-Autosomal dominant, trinucleotide repeat in a coding region
-Progressive choreic movements |
|
|
Term
| Stages of Human Development |
|
Definition
Week 1: fertilization and implantation
Week 2: formation of bilaminar disc
Week 3: formation of trilaminar disc
Week 4-8: Dev. of tissues,organs, body patterning
Week 9-broth: Fetal period |
|
|
Term
|
Definition
-Anterior-posterior axis
-They contain a home box and a homeodomain
-Determine body segments, DNA binding
-Genes expressed earlier show up more anterior |
|
|
Term
|
Definition
-Spatial colinearity: the order of genes in a cluster map to an axis on an embryo.
-Temporal colinearity: the order of genes reflects their expression in time. i.e. 3' genes are expressed earlier
-An example is HOX genes |
|
|
Term
Shh
-Where is it found, what does it do, what happens if it's not there? |
|
Definition
-Released by the notochord
-High concentration results in neurons (NT) or bone in the sclerotome
-Also high Shh in the ZPA
-Loss of Shh can lead to holoprosencephaly |
|
|
Term
|
Definition
-Results from poor formation of tissue
1-Incomplete morphogenesis: syndactyly
2-Redundant morphogenesis: Polydactyly
3-Aberrant morphogenesis: Mediastinal thyroid |
|
|
Term
|
Definition
-Result of unusual forces on normal tissue (i.e. twins or oligohydramnios)
-Can be the result of a malformation, i.e. no kidney formation leads to deformations in Potter's Sequence |
|
|
Term
|
Definition
Syndrome: a bunch of anomalies or sequences; there are similar patterns manifested in in more than one person
Sequence: when an anomaly causes other anomalies to occur |
|
|
Term
| For a teratogen to be a teratogen it must act: |
|
Definition
| -specifically and consistently |
|
|
Term
| 4 Things that affect the effect of a teratogen: |
|
Definition
1) Dose: what concentration, maternal/fetal genotype, etc.
2) Timing: first 2 weeks are all-or-none, most have their effect between 2-8 weeks
3) Maternal factors like diabetes or PKU
4) Physical factors like Ionizing radiation |
|
|
Term
|
Definition
Teratogens that mimic diseases
-Warfarin embryopathy is very similar to chondrodysplasi punctata (trident nose) |
|
|
Term
| Mitochondrial Genome tidbits: |
|
Definition
-Codes for respiratory chain peptides, tRNA, and rRNA.
-No introns, everything has a coding purpose
-Mitochondrial disorders can result from mitochondrial or nuclear gene problems |
|
|
Term
|
Definition
-dysfunctional respiratory chain (energy production)
-affect organs with high energy requirements
-age of onset varies, even in families
-multi-symptom disorders |
|
|
Term
| 4 ways gene therapy can be used |
|
Definition
1) Augment, give the gene back to a diseased cell
2) Directly alter or repair (recombination)
3) Provide a gene that adds missing function or regulates expression
4) Silencing or inhibiting genes (good for trinucleotide repeats) |
|
|
Term
| Two main pathways for gene therapy |
|
Definition
1) In Vivo: direct, all types of cells, but unstable and may need to be repeated
2) Ex Vivo: can persist for life, integrates into genome, but requires cells that divide (not good for neurons) |
|
|
Term
| 3 necessities of gene therapy |
|
Definition
1) Gotta know what the gene responsible is
2) Gotta have a wildtype
3) Gotta have a good way of getting it in there |
|
|
Term
|
Definition
-Pseudo-typed: changing the coat of a virus
-Tropism: how different viruses/pathogens have evolved to target certain cells/tissues |
|
|
Term
|
Definition
Both are integrating methods for gene therapy
-Retrovirus: longterm, stable, only in dividing
-Lentivirus: longterm, stable, all types of cells, a stripped down HIV virus could be dangerous |
|
|
Term
| Non-integrating gene therapy |
|
Definition
-Adenovirus: easy to get into cells, large capacity and persists for a while, but activates immune response
-Adeno-associated: better against immuno, small capacity
-Naked DNA: direct injection, cheap, not super effective and unstable |
|
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Term
|
Definition
-Trithorax group(activates)/Polycomb group (suppresses):bind to the homeobox
-DNA Methylation
-Histone modification
-Nuclear compartmentalization (lamina periphery)
-RNAi (xist codes for an rna that coats and inactivates one of the x chromosomes) |
|
|
Term
| How do we know that male and female chromosomes are different? |
|
Definition
-Through pronuclear transplantation
-M+M=no embryo (androgenetic)
-F+F= no placenta/membranes (gynogenetic) |
|
|
Term
|
Definition
This is an example of gene imprinting. Could also be dominant with low penetrance.
- Only people that inherited the gene from their father have the disease.
-Not x-linked because sons and daughters have it |
|
|
Term
|
Definition
-Hypotonia in infancy, obesity and unsatiable appetite later on
-Due to a deletion on the PATERNAL chromosome 15
-Or due to uniparental disomy (both 15s are maternal, so no paternal 15). |
|
|
Term
|
Definition
-Both chromosomes are from the same parent
-Heterodisomy: one chr. is the mothers maternal and one is the mothers paternal
-Isodisomy: both chr. are from the mother and both are either her paternal or her maternal |
|
|
Term
|
Definition
-Always due to a deletion on the MATERNAL chr. 15
-mental retardation, inappropriate laughing, seizures. |
|
|
Term
| What we learned from the Dutch Hunger Winter |
|
Definition
-Famine caused reduced IGF2 methylation which lead to decreased intrauterine growth
-The children of affected children were also smaller, so the environment changed the genetics. |
|
|
Term
| Prenatal screening vs. prenatal testing |
|
Definition
Screening is noninvasive and has high detection rate, only for trisomy 21/18
Testing is invasive, definitive, and any chromosomal abnormality can be detected |
|
|
Term
| Forms of prenatal diagnosis |
|
Definition
1) Genomic: arrays, karyotyping
2) Analyte detection: a-fetoprotein, hCG
3) Structural survey: ultrasound
4) Infection eval: culture |
|
|
Term
| What happens to the number of alleles as a disease becomes more prevalent? |
|
Definition
-As a disease become more prevalent there are more alleles that contribute to it and they have smaller effects
-Rare diseases generally have one large gene with a big effect |
|
|
Term
| Sensitivity vs. specificity |
|
Definition
100% Sensitivity: no false negatives
100% Specific: no false positives
SPIN SNOUT |
|
|
Term
|
Definition
-Build up of homocysteine due to a defective enzyme
-Results in mental delays, etc
-Treated with drug that is a cofactor for the defective enzyme. |
|
|
Term
|
Definition
-Results in a build up of cystine in the lysosome.
-treated with cysteamine which turns cystine into a cysteine and a cysteine-cysteamine complex. |
|
|
Term
| Non-Mendelian irregularities of complex diseases include |
|
Definition
-Disconcordance between MZ twins
-Parental origins (imprinting)
-Gender dimorphisms
-Age at onset |
|
|
Term
|
Definition
-Odds ratio is an estimation of the risk ratio
-calculate with (a/c)/(b/d) |
|
|
Term
| Ratio vs. Proportion vs. Rate |
|
Definition
Ratio: numerator not part of the denominator
Proportion: numerator is part of the denominator
Rate: proportion over time |
|
|
Term
|
Definition
Prevalence is the number of people with a disease at a given time.
Incidence is the number of new cases over a certain period of time.
Prevalence=incidence x avg duration of disease |
|
|
Term
|
Definition
For infectious teratogens
T: toxoplasmosis (undercooked meat)
O: Syphillus
R: Rubella
C: cytomegalo virus (herpes)
H: Herpes |
|
|
Term
|
Definition
| -Caused by a single point mutation turns glutamic acid to a valine in the B chain. |
|
|
Term
| What links glycolysis and the TCA cycle? |
|
Definition
-Pyruvate dehydrogenase (PAH)
-It converts pyruvate into acetyl CoA |
|
|
Term
|
Definition
-The irreversible reactions are regulated
-So isocitrate dehydrogenase and a-ketoglutarate dehydrogenase
-NADH inhibits, Ca and ADP activate |
|
|
Term
|
Definition
Irreversible rxn: F6P to F1,6-BP
This rxn is catalyzed by PKF-1, which is regulated by AMP, citrate, and F1,6-BP |
|
|
Term
| 4 main steps of β-Oxidation: |
|
Definition
-oxidation (using an FAD)
-hydration
-oxidation (using NAD)
-cleavage (using CoASH) |
|
|
Term
| How Vmax and Km are affected by different inhibitors |
|
Definition
Competitive: Vmax is the same and Km goes up
Non-competitive: Vmax is decreased and Km stays the same
Uncompetitve: only bind to enzymes that are already bound to substrate, both Vmax and Km are decreased. |
|
|
Term
| 5 stages of behavior change |
|
Definition
PC PAM
-Pre-contemplation: Not aware of a problem
-Contemplation: Aware and starting to think
-Preparation: realizes benefit, getting ready
-Action: Doing it
-Maintenance: Doing it for a long time |
|
|
Term
| 4 Theories of behavior change |
|
Definition
-Health Belief Model: Do you know that you need to change?
-Social Cognitive Theory: Access, barriers, affordability, built environment
-Theory of Planned Behavior: change do to intention(planning), also involves control
-Cognitive Behavior Therapy: self monitoring and stimulus control |
|
|
Term
|
Definition
α-priming on leading and lagging strands
β-DNA repair only
Ɣ-mitochondrial
ƍ-primarily lagging strand synthesis
ε-primarily leading strand synthesis |
|
|
Term
| Duchenne Muscular Dystrophy |
|
Definition
|
|
Term
|
Definition
-Microdeletion
-Loquacious |
|
|
Term
| Criteria for invasive prenatal testing |
|
Definition
Advanced maternal age
Previous child with chromosome abnormality
Abnormal serum screening
At risk for single gene disorder
At risk for NTD
Abnormal sonogram (fetal anomalies) |
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