Term
|
Definition
| one mutant allele at each of two different loci |
|
|
Term
|
Definition
| individual with two diffrent mutant alleles of the same locus |
|
|
Term
|
Definition
| only having 1 copy of the gene and being a mutant there |
|
|
Term
| Do de novo mutations matter for recessive disorders? |
|
Definition
| no because they will still not be expressed unless they happened TWICE T THE SAME TIME |
|
|
Term
| Do de novo mutations matter for dominant or x-linked disorders? |
|
Definition
| YES! they will be significant |
|
|
Term
| Penetrance vs expressivity |
|
Definition
penetrance: percent of people that will show the disease if they have the mutation
expressivity: how much the disease comes through, mild to severe phenotype |
|
|
Term
|
Definition
1 in 3,500 births
AD - NF1 gene
50% de novo
cafe-au-lait
5% malignant
tumors of nervous and connective tissue
blindness: lisch nodules on the iris
100% penetrance
VERY variable expressivity |
|
|
Term
|
Definition
different mutant alleles with different mutations
(classic case is CF) |
|
|
Term
| What are the exceptions to allelic heterogeneity? |
|
Definition
consanguineous parents
particular ethnic group
disease has no real heterogeneitylike sickle cell |
|
|
Term
Hardy-
what is affected?
what is unaffected? |
|
Definition
|
|
Term
Consanguinity
Coefficient of relationship?
What is it for a parent and child?
Brother and sister?
Uncle and Nephew? |
|
Definition
Coefficient of relationship?: proportion of genes are shared between two related individuals
Parent and Child is 1/2
Brother and sister is 1/2
Uncle and nephew is 1/4 |
|
|
Term
| Equation for R in consanguinity: |
|
Definition
| (1/2)^n where n is the number of steps of steps away on a pedigree |
|
|
Term
Coefficient of inbreeding (F)
Equation for F?
What about homozygosity for the mutant allele? |
|
Definition
Probability of homozygosity for a specific allele dervied from a common ancestor
Proportion of loci at which a person is homozygous by descent
Multiply R by 1/2
Multiply F by 1/2 |
|
|
Term
| What kinds of proteins are autosomal dominant disorders? |
|
Definition
|
|
Term
| Is homozygosity for an autosomal dominant worse? |
|
Definition
|
|
Term
|
Definition
AD (imcompletely dominant) - Fibroblast growth factor
80% de novo
shortened limbs |
|
|
Term
| How could no parent be affected in an autosomal dominant mutation? |
|
Definition
new mutations
gonadal germline mosaicism
parental phenotype
penetrance
delayed onset
non-paternity
anticipation |
|
|
Term
|
Definition
unstable length mutation, CAG at 4p
disease at 36 repeats
shows anticipation
triploid increase in spermatogenesis not oogenesis |
|
|
Term
|
Definition
1:8000
19q13.3 mutation
progressive muscle weakness
trinucleotide repeat CTG, correlates with age and onset and severity |
|
|
Term
| Where do de novo AD mutations come from? |
|
Definition
| SPERM! at least most of the time |
|
|
Term
| What diseases have been associated with paternal age? |
|
Definition
achondroplasia
marfan syndrome
treacher-collins syndrome
crouzon sundrome
progeria |
|
|
Term
Single Gene traits
What percent occur after puberty?
What percent happen once we hit reproductive age?
What percent of livebirths?
What percent of hospitalized children? |
|
Definition
|
|
Term
| How many autosomal recessive disorder can you name? |
|
Definition
| primary haemochromatosis, mental retardation, CF, retinis pigmentosa, spinal muscular atrophe, blindness, congenital adrenal hyperplasia, medium chain acyl CoA dehydrogenase Def, phenylketonuria, Guacher disease, Smith-lemil-opitz, zellweger, galactosemia, seckle cell, thalassaemia, freidreich, ceriod lupofusinosis |
|
|
Term
What is the risk for a child with birth defect in the general population?
For first cousin?
For brother sister? |
|
Definition
|
|
Term
|
Definition
| osteosclerosis, familial hypercholesterolaemia, detiongenesis imperfecta, adult polycystic kidney disease, multiple exostosis, hereditary motor and sensory neuropathey, neurofibramatotis type 1, hereditary sperocytosis, osteogenesis imperfecta, myotonic dystrophy, Ehlers-Danlos syndrome, marfan syndrome, achondroplasia, dominant blindness, cominant congenital deafness, adult onst cerebellar ataxia, huntington's disease, |
|
|
Term
|
Definition
AD
fibrillin 1 disorder
Skelton, heart eyes affected |
|
|
Term
| What proportion of XLR cases are due to a de novo mutation? |
|
Definition
| 1/3 is the trait is lethal |
|
|
Term
|
Definition
Be Wise Fools GOLD Heeds Silly HOpe
Brutons agammaglobulinemia, Wiskott-Aldrich, Fabrys, G6PD Def, Ocular albinism, Lesch-Nyhan, Duchennes, Hunters, Hemophilia, OTC def |
|
|
Term
|
Definition
|
|
Term
What do we make without SRY?
What do we make with SRY?
What do we need to make external male genetalia?
What regresses the uterus, fallopian tubes and upper vagina? |
|
Definition
ovaries
testes
5alpha-reductase androgen receptor for testosterone and then dihydroesterones
SF-1 and antimullerian hormones |
|
|
Term
| Duchenne Muscular Dystrophy |
|
Definition
X-Linked - deletion (80%)
Lack of dystrophin for muscle and brain neurons,
onset at 3-5 years, 50% cardiac failure, IQ 1SD below mean
Has Gowers Sign
VERY Large GENE |
|
|
Term
Dystrophin gene
How many exons?
What percent of the X chromosome? |
|
Definition
How many exons? 79!
What percent of the X chormosome? 1.5 |
|
|
Term
| Becker Muscular Dystrophy |
|
Definition
X Linked, allelic to Duchenne
Much later onset then Duchenne, milder, reproduction possible |
|
|
Term
|
Definition
X linked
Protease (F9) and cofactors (F8) activate Factor X to form clot |
|
|
Term
|
Definition
Factor 8 (A and rhyme!)
1/5000 - 1/10000
26 exons on gene |
|
|
Term
|
Definition
|
|
Term
| Hemophelias and recombination |
|
Definition
| Factor 8 gene can get inverted in exons 1-22 because of inverted homologous sequences on the same strand |
|
|
Term
|
Definition
X-linked Recessive gene to Xq27.3 FMR1
1:4000 males: mental retardatoin
1:4000 females - borderline IQ
Gene is a transcription suppressor and this suppressor is silenced by CGG repeats
Premutation is >55
Full Mutation has >200
Tends to Increase in oogenesis |
|
|
Term
| Expansive Repeat Disorders |
|
Definition
Huntington >40CAG
Mytotonic Dystropy >80CTG
Friedrich Ataxia >100AAG
Fragile X >200CGG |
|
|
Term
| How many organs should be affected in polyenic/multifactorial traits? |
|
Definition
|
|
Term
What are the reccurence risks for........
chromosomal numerical?
chromosomal structural?
Single Gene Dominant?
Single Gene Recessive?
POlygenic? |
|
Definition
chromosomal numerical? 1%
chromosomal structural? 10% if parent translocation
Single Gene Dominant? 50%
Single Gene Recessive? 25%
POlygenic? 2-5% |
|
|
Term
| Name some polygenic conditions |
|
Definition
Neural tube defects
hydrocephaly
cleft lip
cardiac defects
diaphragmatic hernia
omphalocele
renal agenesis
ureteral anomalies
hypospadias
posterior urethral valves
uterine defects
hip dislocation
limb reduction defects
talipes equinovarus |
|
|
Term
| Incidence for Multifactorial Traits |
|
Definition
|
|
Term
Concordance of monozygotic twins fro
AD
AR
polygenic |
|
Definition
100
100
50-75 (shows environmental component) |
|
|
Term
Cleft Lip +/- Cleft Palate
vs.
Cleft Palate (alone) |
|
Definition
Lip
1/1000 Japan, 1/2000 in U.S. Blacks
Males>Females
counsel on serverity
Palate Alone
1/2000 White, 80/1000 in Native American
females>males
counsel on sex and number of prior affected relatives (more is more recurrence)
MEN GET LIP
Women GET Pallete (women cook!)) |
|
|
Term
| Reccurence Risk and Ease of infection |
|
Definition
| Recurrence Risk is HIGHER if it is the LESS often affected sex |
|
|
Term
|
Definition
Congenital Intestinal Aganglionosis
Higher Recurrence in female proband, long proband and male sibling
Constipation, inability to pass meconium |
|
|
Term
| Adult Onset Polygenic Disorders |
|
Definition
| 8-10% recurrence Risk (higher then just normal polygenic) |
|
|
Term
| Pseudocholinesterase Deficiency |
|
Definition
cholinesterase converts acetylchoine into choline and acetic acid
Usually activity, slow degradation of choline ester drugs
High in Iranian Jews |
|
|
Term
| Alchol Metabolism in Different Populations |
|
Definition
differences in Acetaldehyde Dehydrogenase Deficiency
Japanese > Chinese > Indians |
|
|
Term
Acetaldehyde Dehydrogenase Deficiency
What is the mutation? |
|
Definition
|
|
Term
|
Definition
Phase 1 - Make oxygen intermediates (example is hydroxylation)
Phase 2 - Turn oxygenate intermediates to conjugates products |
|
|
Term
|
Definition
Prophylaxis and treatment of thrombosis
S racemate is more active, metabolized by CYP2C9* which can have very variable alleles
R racemate is metabolized by CYP450 enzymes |
|
|
Term
|
Definition
breaks down warfarin S
Higher numbers are slower breaking down (need lower dose) |
|
|
Term
|
Definition
Warfarin inhibition
Complete inactivation causes multiple coagulation factor defects
A alleles have high activity and therefore lots of warfarin inhibition and therefore Low dose?) |
|
|
Term
| Glucose 6 Phosphate Dehydrogenase Deficiency |
|
Definition
G6PD takes glucose 6 phosphate into HMP Shunt
Deficiency causes lack of NADPH to make glutathione to detoxify oxidants and resulting hemolytic anemia |
|
|
Term
Glucose 6 Phosphate Dehydrogenase Deficiency
A-
B- |
|
Definition
(A is AFRICAN) A-African, 20-30% of hemizygous males affected, activitiy sufficiency for 50 Days
B-(more server) Mediteranean - all hemizygous males susceptible, activity insufficient only 5-10 days after circulation |
|
|
Term
|
Definition
Treats HIV
nucleotide reverse transcriptase inhibitor but can give systemic hypersensitivity reaction
HLA-B*5701 is a good predictor of the hypersensitivity |
|
|
Term
|
Definition
AR
1 in 13,000 in newborns
low phenylaline hydroxylase, tyrosine becomes essential
excess phenylalanine becomes toxic phenylpyruvate (AKA phenylketone) |
|
|
Term
| 3 disorders of phenylalanine hydroxylase |
|
Definition
classic pku
varient PKU
non-pku hyperphenylalaninemia (no dietary restriction needed) |
|
|
Term
|
Definition
| as adults less restrictive diet needed but fetus will be harmed and therefore pregnant mothers MUST have very restricted diet |
|
|
Term
|
Definition
thyroxine 2 SD below mean
elevated TSH from anterior pituitary
1/4000 neonates |
|
|
Term
|
Definition
1/500 middle ear
1/1000 neurosensory
can be AD or AR
GJB2 (connexion 26) in cochlea |
|
|
Term
|
Definition
cystathionine synthase deficiency
low B12
low Folate |
|
|
Term
| Maple Syrup Urine Disease |
|
Definition
| branch chain amino acids low alpha ketoacid dehydrogenase |
|
|
Term
| Screened urea cycle disorders |
|
Definition
citrullinemia, argininosuccinic oxidase
OTC deficiency (not screened) |
|
|
Term
| Screened Fatty Acid Disorders |
|
Definition
Propinylcarnithine; methylmalonic acidemia
acylcarnithine
B-hypohetotic hypoglycemia (medium chain acyl -CoA dehydrogenase deficiency) |
|
|
Term
|
Definition
|
|
Term
Screening Recommendations
Blacks:
Jewish:
Italian and Greek:
Asian:
All: |
|
Definition
Blacks: Sickle Cell
Jewish: Tay Sachs, CF
Italian and Greek: B-thalassemia
Asian: alpha thalassemia
All: CF, Spinal Muscular Atrophy |
|
|
Term
| What diseases have high herterzygosity in Ashkenazim Jews? |
|
Definition
Gaucher 1/13
CF 1/25
Tay Sachs 1/30
Familia Dysautonomia 1/30
Canavan 1/40
Nieman-Pick 1/90 |
|
|
Term
| Hereditary Hemochromatosis |
|
Definition
Iron Overload causing fatigue, abdominal pain, cirrhosis, diabetes, cardiomyopathy, skin bronzing, hypogonadism
95% homozygous Cys282Tyr not the most common mutation but the more deleterious allele
75-90% asymptomatic |
|
|
Term
| A plateau of risk is reached earlier in the |
|
Definition
| variant, not the wild type |
|
|
Term
|
Definition
how many more times the prevalence is in the relative then in the population
higher means more genetic disease |
|
|
Term
|
Definition
10% of all diabetes
Childhood onset
Autoimmune destruction of B cells in pancreas
MZ concordane 40%
DZ concordance 5%
relative risk =35
95% are heterozygous for HLA class II locus at DRB 1
90% lack aspartic at position 57 |
|
|
Term
|
Definition
1% of population
MZ conc - 50%
DZ - 14$
several genes involved
22q11 deleitions (DiGeorge)
child of two parents has recurrence risk of 46%, relative risk is 23
sibling is rr of 11 |
|
|
Term
|
Definition
0.8% of population
15% suicide rate
child of two parents 60%, rr of 75
sibling 25%, rr of 31 |
|
|
Term
|
Definition
1-2% of population
B amyloid plaques
MZ conc 50%
DZ conc 18%
Problem is apolipoprotein E
E4 allele of the worst of these thought 60% still do not get disease
Women get it more oftenh |
|
|
Term
| Mutations are random but not seen in exons - why? |
|
Definition
|
|
Term
| oculodentodigital syndrome |
|
Definition
| nonsense mutation in connexin 43 |
|
|
Term
| What can crossing over between repetitive sequence cause? |
|
Definition
| duplication and deletions! |
|
|
Term
|
Definition
Copy number polymorphism
single nucleotide polymorphism
short tandem repeat polymorphism
variable number tandem repeat |
|
|
Term
|
Definition
| does not allow HIV to invade cells |
|
|
Term
|
Definition
A - N-acetylgalactosamine
B- extra galactose |
|
|
Term
|
Definition
short arm chromosome 6
Complex with linkage disequilibrium |
|
|
Term
|
Definition
MELAS
KSS
PEO
DAD
LHON
Leigh
NARP
MINGIE
MEERF |
|
|
Term
|
Definition
Kearns Sayre
opthalmoplegia, cardiac function loss, sensorineural hearing loss |
|
|
Term
|
Definition
progessive external opthalmoplegia
mitochondrial
progressive ophthalmoparesis in cardinal region |
|
|
Term
|
Definition
mitochondrial
diabetes and deafness |
|
|
Term
|
Definition
neuropathy,ataxia, retinitis pigmentosa, ptosis
dementia |
|
|
Term
|
Definition
| myoneurogenic gastrointestinal encephalopathy |
|
|
Term
| equation for recombination frequency |
|
Definition
|
|
Term
|
Definition
9q34
linked to ABO blood group |
|
|
Term
| What two things are factors of equilibrium? |
|
Definition
| time and recombination frequency |
|
|
Term
|
Definition
grab concordant siblings with the disease, look for alleles they share more than 50% of the time
Finds markers close to disease gene, not necessarily the disease gene |
|
|
Term
| highly discordant sibpair method |
|
Definition
| grab siblings that only 1 has the disease and find where the siblings are different |
|
|
Term
|
Definition
| DNA is extracted from affected individuals and compared to control group |
|
|
Term
|
Definition
| melts the DNA at an origin of replication |
|
|
Term
|
Definition
1 - polA - major repair, replaces RNA primer
2- polB - replication restart
3- polC replicase
4 - dinB translesion replication
5 - umuD2C - translesion replication |
|
|
Term
| What makes the replication RNA primer? |
|
Definition
DNA primase
Can start a polynucleotide by joining two nucleosides together |
|
|
Term
|
Definition
builds 5 to 3
adds the 3 phosphate nucleotide and only keeps 1 of these phosphates as the backbone |
|
|
Term
| Proofreading of DNA polymerases |
|
Definition
1 - Replaces RNA primer with 5 to 3 exonuclease
3 - builds 5 to 3, proofreads 3 to 5 |
|
|
Term
|
Definition
Helicase which wraps around and undoes helix
single stranded binding proteins bind to one side
topoisomerse gets rid of torsion by clipping and rotating it |
|
|
Term
|
Definition
Connectors: hold the replisome together
Clamps: keep DNA Pol 3 on DNA until it hits double stranded DNA |
|
|
Term
|
Definition
| Joins together Okazaki Framents, uses ATP for the phosphate needed |
|
|
Term
|
Definition
| inhibits DNA gyrase (prokaryotic toposomerase) |
|
|
Term
| What makes sure that mismatch repair mechanisms in DNA replication know which is the template strand? |
|
Definition
| nicks in the backbone of the nontemplate strand |
|
|
Term
| Where do we have early replication? |
|
Definition
|
|
Term
|
Definition
cytosine to uracil
5 methyl cytosine to thymine
adenine to hypoxanthine
guanine to xanthine
nucleotide exicision repair |
|
|
Term
|
Definition
most frequent type of DNA damage
guaniine or adenosine become just phosphate backbone
correct with base excision repair |
|
|
Term
| base excision repair vs nucleotide excision repair |
|
Definition
base only cuts out 1 base, glycosylases, AP endonuclease, used for depurination
nucleotide cuts out whole region, use DNA pol and ligase, Uvr |
|
|
Term
| Replication Forks and DNA Damage |
|
Definition
| Replication stalls and fixes the damage |
|
|
Term
| Transcription and DNA repair |
|
Definition
actively transcribed genes are more prone to repair, signal is RNA pol stall
done by Mfd |
|
|
Term
|
Definition
1. Cell shrinkage and chromatin condensation
2. Membrane bledding
3. Nuclear collapse
4. Apoptotic body formation |
|
|
Term
| When in meiosis does crossing over occur? |
|
Definition
|
|
Term
|
Definition
Generalized or homologous
site specific
somatic |
|
|
Term
| site specific recombination |
|
Definition
| specific sequences invade the virus and bacterial DNA at specific places |
|
|
Term
| Homologous Recombination Steps |
|
Definition
Leptotene - condensed chromatin
Zygotene- begin pairing
Pachytene - synaptonemal complex extends entire length of chromosome
Diplotene - separate but held together at chiasmata
Dikinesis - all 4 visible, chiasmata remain |
|
|
Term
| How is recombination initiated? |
|
Definition
| double stranded breaks in one DNA dublex |
|
|
Term
| Homologous recombination biochemistry |
|
Definition
1) Spo11 and Mre11 cut DNA and degrade 5 to 3
2) Forms D structure using rec A
3) Branch migration
4) double holiday junction formed
5) DNA cut to possibly form crossovers |
|
|
Term
|
Definition
formed after double stranded break in DNA
has an axis of cohesins and loops of DNA for each pair of sister chromatids
Pairs connected via Zip proteins |
|
|
Term
|
Definition
| using recombination to fix mismatched bases |
|
|
Term
| Somatic Recombination and recessive genes |
|
Definition
| can lead to localized areas of homozygous recessive state and disease, possibly tumour supressing genes |
|
|
Term
| Immunoglobulins crossing over |
|
Definition
| often acheieved through unequal somatic recombination to produce high variability in globulins |
|
|
Term
|
Definition
| Accomplished by using recombination to bring different DNA domains together |
|
|
Term
|
Definition
| Accomplished by using recombination to bring different DNA domains together |
|
|
Term
| Why care about sister chromatid exchange? |
|
Definition
| It has no significance as they are identical but help assess mutagens and carcinogens |
|
|
Term
| Repetitive Sequences and double strand breaks |
|
Definition
| double strand breaks can be repairs through repetitive sequences although often it will often cause a deletion of the sequence between the repeats and the loss of one of the repeat sequences |
|
|
Term
|
Definition
1. DNA type elements (no RNA intermediate required)
2. Retroelements (2 subtypes, have LTR's or lack LTR's) |
|
|
Term
|
Definition
| enzyme helping element insert, usually encoded by transposon itself |
|
|
Term
| What percent of human DNA is transposons? |
|
Definition
|
|
Term
| Positive and negative effects of transposalable elements |
|
Definition
Positive: Genetic variability
can turn on and off genes
Negative: cause deletions and duplications
move host sequences
interrupt host sequences |
|
|
Term
| transposons and recombination |
|
Definition
| cause the crossover at the wrong places and cause duplications and deletions |
|
|
Term
| What do inverted repeats do when recombination occurs? |
|
Definition
| they invert region between them! |
|
|
Term
| What do direct repeats do when they loop and recombine? |
|
Definition
| releases material between |
|
|
Term
|
Definition
| has two inverted terminal repeats and is flanked by direct repeats after inversion |
|
|
Term
|
Definition
2 copies of single stranded RNA
integrated is called a provirus
are retrotransposons which acquired an envelope |
|
|
Term
|
Definition
gag, pol and env
pol requires a ribosome frameshift
env is made by mRNA splicing
3 proteins are cut up into many other proteins by proteases |
|
|
Term
|
Definition
2 base pairs are lost from each end
done by retroviral integrase
target site makes direct repeats |
|
|
Term
| 3 categories of retroelements |
|
Definition
LTR retrotransposons- has LTR, target repeats 4-6BP, ancient retroviral infections, use RT, have introns
non LTR retroposons - 7-21BP target repeats, use RT, could be LINEs
nonautonomous SINE's - no RT coded for in them, still use it! |
|
|
Term
|
Definition
LINES are longer and have reverse transcriptase coded for (sometimes it is broken), LInes are translated where as SINES are only transcribed
SINEs are related to RNA polymerase 3 transcripts (the SRP in humans) |
|
|
Term
| LINE and SINE integrations |
|
Definition
| use nick in DNA, cDNA grows from RNA template and then cDNA is copied |
|
|
Term
|
Definition
| virus is a vector to transport the host NDA |
|
|
Term
|
Definition
sex between prokaryots with sex pili (coded for by F+ gene)
Sex is between F+ and F-, thought F- becomes F+ after |
|
|
Term
|
Definition
| pick up DNA from environment |
|
|
Term
|
Definition
| foreign DNA incorporated in Eukaryotic cell |
|
|
Term
blastocyst
chimera
mosaic
determination
differentiation
embryonic germ cells
embryo
epiblast
hypoblast
morula
gastrulation
inner cell mass
morphogen
mosaic development
zygote |
|
Definition
morula - 8-16 cells, implants to uterus
blastocyst - multicellular mass of about 60 cells, with ICM and trophoblast
chimera - embryo made of 2 or more cells lines with different genotypes
mosaic
determination
differentiation
embryonic germ cells
embryo
epiblast - inner cell mass that makes embyo
hypoblast - gives rise to fetal membranse (amnion)
gastrulation - makes 3 germ layers
inner cell mass - makes hypoblast and epiblast
morphogen
mosaic development - mutation causes 2 of more genotypes
zygote
fetus - between G9 and birth |
|
|
Term
| What four processes allow for development of an embryo? |
|
Definition
| proliferation, differentiation, migration, apoptosis |
|
|
Term
|
Definition
| produced by cells in a particular region and that diffuses to create concentration gradients, controls determination |
|
|
Term
|
Definition
| plasticity goes down with time |
|
|
Term
| two insemmination methods |
|
Definition
culture egg with sperm
intracytoplasmic sperm injection |
|
|
Term
|
Definition
|
|
Term
|
Definition
| implantation outside the uterus |
|
|
Term
|
Definition
pasrt of blastocyst that becomes the placenta and chorion
cytotrophoblast (cells around ICM)
and synctiotrophoblast (becomes placent) |
|
|
Term
|
Definition
6th day after fertilization
trophoblast produces enzymes that allow blastocyst to burrow |
|
|
Term
|
Definition
| 14-16 days after fertilization |
|
|
Term
|
Definition
| high grade is bad, shows fragmentation |
|
|
Term
| 60% of day for embryos have....... |
|
Definition
|
|
Term
| aneuploid and mosaic with age |
|
Definition
aneuploid is increases with age
mosaic is constant |
|
|
Term
| specification vs determination |
|
Definition
| specification is reversible |
|
|
Term
| regulative vs mosaic development |
|
Definition
| regulative is early and if a cell is lost is can be compensated for |
|
|
Term
twincs
dichorionic
monochorionic and diamniotic
monoamniotic |
|
Definition
0-3 days dichorionic - completely separate -35%
4-7 days monochorionic and diamniotic - 2 ICM in 1 trophoblast - 65%
after 7 days - monoamniotic - rare, one ICM |
|
|
Term
| embryo and transcription factors disease |
|
Definition
synpolydactyly - extra digits and webbing
mutationi n HoxD13 |
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Term
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Definition
signal from optic cups induses placode to develop
hetero mutation -aniridia (no iris)
homo mutation - eyeless |
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Term
| Glucose and pyruvate in development |
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Definition
| pyruvate is essential for the 1st cleavage division and glucose only used as 8 cell stage |
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Term
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Definition
| remove intracellular molecular breaks that restrains progression in G1 phase |
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Term
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Definition
mitogen gets us through cell cycle
growth factors makes sure we grab the nutrients needed |
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Term
| 3 major control sites for cell cycle |
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Definition
G1/S
G2/M
metaphase/anaphase |
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Term
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Definition
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Term
| mitogen and entry to S phase |
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Definition
| mitogen to RAS to MAP kinase to DNA to make Myc to activate G1-CdK to inactivate Rb to active E2F to Cyclin E and Cyclin A |
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Term
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Definition
| link sister chromatids into one mechanical unit |
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Term
| DNA damage and arrested the cell cycle |
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Definition
| Damage to ATM kinase activative to ChK1 kinase activation to phosporylate p53 releasing it from Mdm2 which goes to DNA to make p21 which inactivates G1/S-Cdk |
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Term
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Definition
| Cdk hooks up with cyclin in t loop and gets phosphorylated |
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Term
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Definition
D - past G1/S restriction
E/A - initiation of S
B - transition from G2 to M |
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Term
G1 CDK
G1/S cdk
S-CDK
MCDK
APC/C |
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Definition
G1 CDK - cyclin D, tests environment
G1/S cdk - cyclin E, DNA damage
S-CDK - cyclin A, DNA damage
MCDK - cyclin B
APC/C - anaphase promoting complex, tests chormosomes attached to spindle |
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Term
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Definition
anaphase promoting complex
ubiquitinates M cyclin and securins which hold sister chromatids together |
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Term
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Definition
| causes Arf production and release of Mdm2 from p53 causing cell cycle arrest of apoptosis |
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Term
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Definition
accident, disrupted homeostasis
types: coagulation - MI
liquefaction -softening
caseous - cheesy |
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Term
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Definition
| swelling, repture, cytoplasm spilled |
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Term
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Definition
| nuclear propidium iodide staining |
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Term
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Definition
| shrinkage, blebs, dna fragmentation, loss of adhesion, engulfed by macrophages |
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Term
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Definition
loss of junctions
skrinkage
blebbing
chrmoatin hypercondensation
apoptotic bodies |
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Term
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Definition
looks for Annexin (binds to phosphoserine)
Caspase 3 activity
TUNEL assay - DNA fragmentation |
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Term
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Definition
cystine aspartate specific proteases
procaspases are cleaved and then go cleave proteins and nuclear lamin |
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Term
what executioner caspases degrade?
what activates them? |
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Definition
cytoskeleton, golgi, nuclear proteins
initator caspase |
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Term
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Definition
| Bcl2 sensors to Bax and Bak to mitochondia which realeases cytochrome C making Aparf1 active and apoptosome which activates caspase 9 |
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Term
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Definition
| Fas or TNF receptor to DISC to active caspase - 8 to procaspase 3 to active caspase 3 |
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Term
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Definition
Proapoptosis - Bax and Bak, Bad, Bim, Bid, Puma, Noxa
antiapoptotic - Bcl2 and Bcl-x |
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Term
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Definition
| is actually pro survival!! |
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Term
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Definition
| large release of Ca2+ from ER can signal cytochrome C release |
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Term
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Definition
| parts of Bcl2 family that are the transmembrane proteins that releases cytochrome c from mitchondrial intermembraneous space |
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Term
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Definition
| inhibitors of apoptosis, they block caspases that were spontaneously made and are turned off by proteins released from mitochondrial intermembranous space |
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Term
| 3 ways to block apoptosis |
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Definition
1. survival factor activates gene regulatory protein TF making Bcl2
2. survival factor activates Akt kinase which activates Bcl2
3. survival factor activates MAP kinase which inactivates Hid an anti-IAP |
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Term
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Definition
| apoptosis from lack of EM mediated cell contact |
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Term
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Definition
transcription factor for:
Bax: apoptosis
p21 - G1 arrest
GADD45 - repair
FAS and IGBP-3- apoptosis |
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Term
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Definition
oncogenes are dominant and are gain of function mutations
TSG are recessive and are loss of function mutations |
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Term
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Definition
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Term
| what will activate Mdm2 thereby inactivating p53? |
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Definition
| growth factors, TGFbeta to Smad2/3 |
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Term
| how to make a proto-oncogene into an oncogene |
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Definition
point mutation
regulatory mutation
gene amplification
chromosome rearrangment |
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Term
| Abl proto oncogene in chronic myelogenous leukemia |
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Definition
| Bcr gene on 22 and Abl on 9 are translocationed and fused |
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Term
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Definition
| DNA damage, hyperproliferation, telomere shortening, hypoxia |
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Term
| DNA virus causes cell proliferation by activating.... |
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Definition
E6 - inhibits p53 trancripiton of P21
E7 - binds Rb protein allowing transcription of cyclin E |
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Term
| DNA virus causes cell proliferation by activating.... |
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Definition
E6 - inhibits p53 trancripiton of P21
E7 - binds Rb protein allowing transcription of cyclin E |
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Term
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Definition
Cetuximab - binds EGF receptor
Trastuzumab - binds to EGF itself
NOTE: if mutation was downsteam, these drugs will be worthless |
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Term
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Definition
| mesodermal, more agressive, from soft tissue, connective tissue |
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Term
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Definition
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Term
|
Definition
| neoplasm from more then one cell type |
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Term
|
Definition
| neoplasms from more then one germ layer |
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Term
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Definition
| resemble primative embryonic tissue |
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Term
Hypertrophy
hyperplasia
metaplasia
dysplasia
pleomorphism
anaplasia |
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Definition
Hypertrophy - big
hyperplasia - lots of cells
metaplasia - change in form/differentition
dysplasia - disordered, abnormality (orientation)
pleomorphism -variaibility in size and shape
anaplasia - reversal or failure of differentiation |
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Term
|
Definition
T - size
N - nodes
M - metastasis |
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Term
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Definition
level of anaplasia or differentiation
higher is more undifferentiated and worse |
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Term
|
Definition
evade apoptosis
get self sufficient growth
insensitivity to anti-growth
tissue invasion
limitless replicative potential
angiogenesis |
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Term
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Definition
autocrine
overexpresison of EGF
mutations in signaling (Ras)
upregulated TF like Myc
activate cyclins |
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Term
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Definition
constituatively active as if GF was always there, cannot hydrolyze GTP off it
Activate Map-Kinase Pathway |
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Term
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Definition
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Term
| insensitivity to growth inhibitory signals |
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Definition
| 2 hit system to tumor suppressor genes |
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Term
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Definition
retinoblastoma
hypophosphorylated binds to E2F and blocks transcription of S phase genes
hyperphosphorylates happens by cyclins D/E and allows E2F to promote S phase genes |
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Term
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Definition
not present in colorectal cancers and therefore allows B catenin to be a TF and proliferate
Normally WNT signals break APC off Bcatenin and allow proliferation |
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Term
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Definition
not active early in cancers but it is active late in cancers
allows the mutations to accumulate and then allows the cell to survive forever |
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Term
shortened telomeres
with p53
without p53 |
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Definition
with p53 - senescence
without p53 - bridge fusion break cycles and aneuplodiy |
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Term
| how doyou induce angiogenesis? |
|
Definition
hypoxia to HIF1alpha (normally inhibited by VHL)
HIF1apla TF for VEGF |
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Term
|
Definition
| p53 activates the expresison of thrombopondin 1 an anti-angiogenetic molecule |
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Term
| ability to mestastasize requires: |
|
Definition
losing E cadherin
degrade matrix with MMPs
attachment to new ECM components with adherins and integrins
migration of tumor cells |
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Term
|
Definition
epithelial to mesenchymal transition
seen by loss of E cadherin
allows the cell to travel! |
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