408 terms

Genetics Part II

3 types of chromosomes based on centromere
metacentric, submetacentric, and acrocentric
long arms has what letter
short arm has what letter
metacentric has what structure
centromere at center, p=q
acrocentric has what structure
no P. Just satellite structures
satellite structres encode for what
submetacentric has what structure
p < q.
what is euploidy
polyploidy in multiples of 23
what is aneuploidy
+ or - not in multiples of 23
two forms of euploidy
triploidy and tetraploidy
what is triploidy
there are three copies of each chromosome. (69) Not compatible with life. NOT TRISOMY
what is tetrapoloidy
4 copies of each chromosome (92). Lethal.
what are the two forms of aneuploidy
monosomy and trisomy.
what is monosomy
loss of a chromosome. Not compatible with life unless its an X.
what is trisomy
have an extra chromosome (47). Not triploidy
what is the syndrome of monosomy at X
turners syndrome
trisomy at 21 is
downs syndrome
trisomy at 18 is
edward syndrome
trisomy at 13 is
patau syndrome
anueploidy monosomy of X is
turners syndrome
anueploidy trisomy at X (XXY) is
Klinefelter syndrome
downs, trisomy at 21, how does it arise
meiotic I nondisjunction in oogenesis
how to diagnose trisomy
interphase FISH
risk factor for downs
maternal age
how to get trisomy at 18 and 13, mechanism
also nondisjunction during oogenesis
edward syndrome symptoms
clenched fist, rock bottom feet, low ears and small jaw, congenital heart defects
patau syndrome feuttures
polydactaly, cleft lip and palate, microphthalmia, heart anaomolies
downs feutures
shrot, depressed nasal bridge, single palmer crease
tuners kids are males or females
alywas female
klinefelter kids are male or female
XXY, always male
turner kids feutures
short, webbed neck, streak ovaries (infetile) and amenorrhea (no mensturation).
turner people body/genetic composiiton
they are mosaics. some are 45 X, some ar 46XX and 47XXX.
turner and barr body's
none. 45X has no inactivated X chromosme
klinefelter feutures
testicular atrophy, female hair distribution, infertility, gynecomastia
klinefelters and barr bodies
oddly, see a barr body in males. kind of a defining feuture.
what cells can you check for the barr bodies
buccal mucosal cells
is turners always from nondisjunction of meiosis 1
nope. it can be from Meiosis I when homologous do not separate OR from meiosis II when sis chromatids do not separate
meiosis I nondisjunction produces the same or different copies of maternal chromosomes in a cell
meiosis II nondisjunction produces the same or different copies of maternal chromosomes in a cell
downs sydnrome is NDJ of meiosis I or II
meiosis I nondisjunction in the dad gives what disease
so what nondisjunctions cause klinefelters
NDJ in I or II of mom. OR NDJ I in dad
why not meiotic NDJ II in dad
that would give XYY
when do we see somatic mosalicism in terms of chromosome number
nondisjunction in the somatic cells during emvryonic development.
so downs syndrome from NDJ in male or female
types of translocations
reciprocal and robertsonian
explain a reciprocal translocation
two non-homologous chromomes swap a part. Cell still has same genetic material, just some genes have swapped places
effects of reciprocal translocation
SOMATIC CELL: can have no effect (silent), can cause cancer. GERM CELL: can cause abortion
give two cancers that occur this way
CML and burkitts lymphoma
CML what type of tranlocation
9 to 22 on philadelphia chromosome.
this translocation connects what
bcr and abl
what causes burkitts lymphoma
translocation 8 to 22
so a reciprocal translocation alternate segragation during meiosis produces what
normal gametes. Its balanced material just like parent. The fertilized zygote will just carry the translocation
so a reciprocal translocation adjacent segragation during meiosis produces what
results in unbalanced gametes, partial trisomy and partial monosomy gametes. upon fertilization get abortion.
3 outcomes from translocation carrier babies
normal, translocation carrier child, aborted child
which chromosomes can have a robertsonian translocation
13, 14, 15, 21, 22
what are these chromosomes considered
acrocentric chromsomes
what is lost at a robertsonian translocation
the satellite structure (rRNA)
what actually occurs in a robert transl
two long (q) arms fuse.
gametes (post meiosis) after a robertsonian translocation
of the four. 2 are ok. 1 is normal and one is a balanced translocation carrier (alternate segragation). 2 from the adjacent segragation will be bad. They will both have trisomy. one will be aborted one could cause DS
DS from rob trans karyotype looks like what
its trisomy, but technically 46 XX. the extra chromosome 21 is there but its the long arm attached to the long arm of 14
DS from robs trans is a result of adjacent or alt segragation
two microdeletion syndromes from large deletions
wolf-hirshchhorn and cri du chat
wolf hischorn is a deletion where
cri du chat is a deletion where
feutures of a cri du chat syndrome
cat like cry, speech problems, and microcephaly
how to test for cri du chat
other name for diGeorge syndrome
velocardiofacial syndrome
what causes velocardiofacial syndrome
microdeletion on chromosome 22q
digeorges feutures
heart defects, no thymus, cleft lip/palate, learning disability
deletions on chromosme 15 cause what
angelman & prader willi syndrome
deletion of maternal 15 gives
deletion of paternal 15 is
prader willi
wolf hirschhorn feutures
facial anomolies and widely spaced eyes. cardiac and metnal problems
ch 11 microdeletion causes
WAGR syndrome
WAGR syndrome has
wilms tumor, aniridia, genitourinary malformations, retardation
name the 2 types of inversions
pericentric and paracentric
which involves the centromere
problems that arise from inversions
usually ok, silent
how to check for inversions
karyotype. Look for banding.
when can inversions be dangerous
if during meiosis. It can lead to a deletion of repetition of DNA segments.
what does this lead to
phenotypically nothing, but can cause abortion
what are isochromosmes
deletion of one arm of a chromosome and duplication of the other arm to replace it
what disease could be from an X isochromosome
turner syndrome.
what is a rind chromosome
when a chromosome loses genetic material at the terminal portions and the ends fuse to make a ring
what is the calculation for allele frequency
P + Q = 1
what is the calculation for genotype frequency
P2 + 2pq + q2 =1
p =1 with what sort of disease
autosomal recessive. they are so rare
if given incidence, how can we get q for an autosomal recessive
q = (srt) (I)
CF incidence is 1/2500. Find affected homozygots and hetero carriers
homo zygotes is sqrt of 1/2500. = 1/50.

hetero carriers are 2pq. p=1. so 2q. = 1/25
for auto recessive q=
sqrt of I
for X recessive, q =
auto dominant Incidence = (in words)
heterozygotes + homozygotes
in equaition form
I = 2q or q =.5I
4 assumptions of hardy weinberg equillibrium
1) population is large 2) Random mating 3) no new mutation 4) no migration
4 things that cause genetic variation in populations
1) New mutation 2) Natural selection 3) Genetic Drift 4) Consanguinity
heterozygote advantage is auto dominant or recessive
auto rec
what diseases are protective against malaria
SCA and B-thalasemia
what is reproductive fitness
ability to get to age and reproduce.
a disease were repro fit is, and why
Tay Sachs, do not get to age of repro
what is genetic drift and what is it about
not migration. its allele drift. In a large population, an allele freq should be pretty stready. In a small one its all over the place
describe the founder effect
in a community thats small, a new person comes in with a new allele. Its gonna increase in freq
describe consanguity
relatives mate. higher incidence of disease
what spec does consanguinity increase the chance of
do multifactorial inheritance diseases follow mendelian patterns
distribution of trats when something is polygenic
normal bel shaped curve.
but are diseases of multifactors bell shaped?
nope. either you have it or not.
eqn for disease susceptibility with genes and environment
what is liability
all the factors that contribute to the disease
what is threshhold
the limit to which we are affected
is this threhold the same for everybody?
nope, our genes and environemnt move it
what is familial relative risk
the closer the relative with the diease, more likely we will get disease
relative risk ratio (lambda r) means what
the familial aggregation of a disease (relative to population)
how to get it
prevelance of disease in relatives / prevelance in total populaton
what does a high lambda r mean
greater familial aggregation
what does lambda r = 1 mean
same ilkelyhood of getting it as population
if more than one close relative is affected, does our chance increase
can the threshold on the curve be diff for the same disease between men and women
yep. so women are less likely for a disease, their threshold is further to the right. need more bad genes/symptoms to get it
cancer is a genetic disease T/F
True. but more are caused by environment
Eqn for heritibility
Heritibility = genetic variance/total variance
monozygotic twins are (ovum)
from one ovum
how similar are they
dizygotic twons are (ovum)
from two ovum. 2 sperm, 2 eggs
how similar are they
like normal siblings (50%)
what does concordance mean with twins
both twins have the same disease
twins and discordance mens
one has it, not the other
which has more of an environmental input, concordance or disconrdace
using twins to get heritibility, whats the eqn
H^2 = (variance in DZ-variance in MZ)/(varianve in DZ)
what does the odds ratio tell you
risk of getting disease when you have a marker that has an assoc with the disease
eqn for odds ration
patient has alleles 1-A and 2-B. Controls have 1-C and 2-D. AD/BC=Odds ratio
which diabetes has a strong genetic componant
type I
familial alzheiumers chromosomes
1, 14, 21
gene on chromeomes 1, 14, and 21
1: presenilin-2 14: presenilin-1 21: amyloid precursor gene
sporadic for of AD on what chromosome
gene on 19
yellow agouti mice have a problem with
a-MSH binding to meanocortin 4 receptor
leptin protein def absent in
obese people
leptin protein receptor absent in
leptin comes from where
released from fat tissue
wheren is the leptin receptor
on the arcuate nucleus
arcute nucleus releases
MSH binds to
the hypothalmus
hypothalmus does what
stops want for food
mutations are a big problem when they happen at what point
during the S phase
explain why we might get an error through tautomerism
Thymine has a rare enol form. This enol for binds with a G
DNA pol corrects itself how
3' to 5' exonuclease activity
two types of frameshift mutations
insertions and deletions
frameshift mutations test to occur where
areas where there are base repeats
why at these spots
there could be a slipping of the DNA polymerase or a loop/kink can form
three types of spontaneous lesions
deamination, depurination, oxidative damage
which is most common
what happens in depurination
break glycosidic bond between base and sugar. sugar-phosphate backbone remains. leaves an AP site (apurinic)
deamination is what process (basic)
lose an amine group
what base deaminates
when cytosine deaminates, what happens
it turns to uracil and will pair with a T. but its easily fixed
what if the cytosine is methylates
it'll deaminate into a T. T is then bound to G. could end up repairing either one
what does oxidative damage do to nucleotides
adds oxygen groups
oxo-guanisine binds with
transition is
purine to purine
transversion is
purine to pyrimidine
UV light can lead to what
covalent linkages between adjacent bases.
problem with covalent linkages
blocks replication
two types of linked dimers
cyclobutane pyrimidine dimer (CPD) or 6-4 photoproduct (6-4 PP)
three repair types
base excision, nucleotide excision, mismatch repair
base excision repair general idea
a DNA glycosylase cuts out a single base leaving an AP site. then repaired
nucleotide excision repair
removes more than one, many nucleotides. bulky non-coding lesion
mismatch repair
this is post-replication repair. shows strand discrimination. MMR protiens pick up what was missed by proofreading. cut it out, fill it in, slear
how do proteins know which strand when discriminating strands
whats the worst type of damage to repair
double strand breaks
how to fix double strand breaks
either Non-homologous end joining (common) or recombinatorial repair (uses homologous chromosome)
whats the syndromes where out DNA repair genes are mutated
bloom syndrome, ataxia telangiectasia, xeroderma pigmentosum, HN colon cancer
bloom syndrome a defect in what gene
BLM gene (DNA helicase)
bloom syndrome symptoms
narrow chin, facial rash to sun, high cancer rates
ataxia telangiectasia gene
ATM codes for
a ser/thre kinase for DNA repair
symptoms of ataxia telangiectasia
cerebellum, ocular, cancer risk
xeroderma pigmentosa gene
many of em. Nucleotide excision repair genes
xeroderma pigmentosa symptons
extreme sun sensitivity, and skin cancer prone
hereditary nonpolyposis colon cancer results in
microsatellite instability
what protein mutations lead to breast cancer suseptibility
BRCAs involved in what
NHEJ and double strand break repair
does a threshold model apply to cancer
nope, not a single quantitative trait
cancer and progression and evolution
progressive aggressiveness is selected for.
the fact that risk of cancer increases with age means
that its prob the consequence of multiple independant events
do cancers arise from a single cell?
yes, most of the time. Can be polyclonal cell line
how do we know they're monoclonal
1) same x-inacitvation in the tumor. 2)same chormosomal mutation in all cells. 3) in the case of a multiple myeloma, all the B cells are the same
3 TYPES of cancer causing genes
oncogenes, tumor suppresor genes, repair genes
oncognes normally
promote growth
tum supp genes normally
inhibit growth
repair genes normally
limit mutations
oncogenes are what before they are oncogenes
proto-oncogenes if normal
major cell proliferation pathway (main oncogene)
Ras works how
growth factor to TK receptor. P-RAS,GTP. When bound to GTP activates MAPK cascade, and acticted TF's and drive cell proliferation.
TKs are protooncogenes
if the TK is mutated so that its constituitivly on can lead to cancer. accelerator stuck to the floor board.
2 examples of protooncogene TK receptors
Her2 and EGF receptors
how can a DNA event lead to a physically dimerized TK receptor
chromosomal tranlocation can link, lets say tropomysoin dimer to the TK and keep it dimerized)
burkitts lymphoma is a translocation of
ch 8 and 22
burkitts details
Myc (protooncogene) fused witht he promotor of an Ig. So inapporopriate expression of it
philly chromosome translocation
9 and 22
9 to 22 links
how does bcr-abl work
Abl is a TK with an inhibitory region called SH3. Bcr interferes with the SH3. and get autoactivation of the Abl TK
how does gleevec work, and other name for it
iminitamab, it inhibits the TK of Abl
how does RAS become an oncogene
a point mutation that keeps it bound to GTP and always on. Or a mutation to the GTPase activity.
a way protooncogenes are overexpressed in cancers are through
double minute chromosomes. these are extrachromosomal DNA fragments. EGFR works this way
what are homogeneouslt staining regions
the chromsome can cope a gene a couple times on itself and you see it through staining.
are oncogenes gain or loss of fn
tum supp genes are gain or loss of fn's
wilms tumor is a tumor supp gene mutation on what chromosome, what gene
Chr. 11, WT1 gene
crossing a normal cell and a wilms tumor cell together gives you a normal or tumor cell
what does this imply
wilms tumor is a loss of fn that can be fixed with normalcy. in this case it got a normal ch 11 WT1
so what is the two hit hypothesis
we are diploid for out genees. we need to lose both to get the tumor
is this sporadic or familial where we need two mutations
what about familial wilms tumor
they are born with one mutation. so only need one somatic mutation. AKA Loss of heterozygosity
which checkpoint decides whether to divide or not
main regulator of this chpt
what does Rb do
inhibits E2F
what inactivates Rb to allow division
CDK4, by P-Rb
what regulates the CDK
mutation of Rb gives
retinoblastoma (childhood cancer)
what chromosome is Rb on
Chr. 13
is Rb familial or sporadic
can be either. one requires one hit (loss of hetero), one requires 2
Loss of Rb leads to
uncontrolled G1/S cause E2F is always on
p16 loss leads to what disease
dysplastic nevus syndrome (pre malignant melanoma)
what does p16 do
inhibits CDK, which phos's Rb to turn it off (allows E2F on)
gain of fn of what in this path leads to G1/S drive
CDK/ClnD overexpression leads to path on (these would be oncogenes)
master tumor supressor
what turns p53 on
stress/ DNA damage
what does p53 do
activates apoptosis and stops G1/S
what activates p53
ATM (ataxia telangiecsta). It P's p53 stablizing it
p53 stops G1/S how
activate p21 by phos (ATM). p21 is an inhibitor of CDK (which inhibits Rb)
other than arresting G1/S, how else does p53 work
in pausing G1/S....it activates DNA repair stuff. if doesn;t work, it will drive expression of genes for apoptosis
p53 has 3 possible effects on the cell
pro-apoptosis genes, DNA repair genes, G1/S arrest
inherited hetero mutation to p53 leads to this disease
Li-fraumeni syndrome. leads to many diff cancers (but not 100% penetrant)
are most colon cancers familial or non-familial
name one inherited/familial colon cancer
FAP, familial adenomatous polyposis (lots of polyps on the colon)
what gene is problematic with FAP
what does APC do
APC is an inhibitor of B-catenin (through direct physical contact)
when APC blocks b-Catenin, what happens to transcription
blocks it
so FAP, what happens
APC is mutated. B-catenin is constituituvly on. drives transcription.
but also another mutation can cause FAP
a mutation to b-catenin so that it doesn't respond to APC inhibition
so either loss of fn of: or gain of fn of:
Loss of APC. Gain of B-catenin
explain mutual exclusivity and FAP
APC or b-catenin. don't have both. no selective advantage of both
which colon cancer is from damaged DNA repair genes
HNPCC. hereditary nonpolyposos colon cancer
FAP patients have many or few polyps
many. slow cancer development but since so many liklihood is high
HNPCC have many or few polyps
few, but the few develop cancer quickly
BRCA causes cancer in which of teh three ways
lack of DNA repair
is BRCA sporadic or familial
which breast cancer gene is sporadic
familial hypercholesterolemia if a problem with
LDL receptor
how to treat
statin (inhibit HMG coA reductase) to stop cholesterol synthesis as well as a oral resin that bind ti=he bile acids in the GI and stop absorption
how to treat HbS
aim to replace (y) for (b). So hypomethylate the gene for HbF
problem with homocystinuria
the enzyme is mutant and cannot bind its co-factor well enough
treatment stragety
add exogenous co-factor and some will bind. Should be enough
PKU can be a problem in what
either defect in enzyme itself, or defect in cofactor production
ultimate treatment
low phenylalanine diet
urea cycle disorder problem
cannot remove ammonia
metabolite diversion. avoid protein diet and also divert ammonia to glycine synthesis (sodium benzoate)
hemophelia A a def in
facvor VIII (8)
protein replacement therapy
protein stability is improved by doing what
PEGylating. Its a carb moiety.
what diseases that can be treated with a pegylated enzyme replacement
gaucher disease & Fabry disease
so whats the treatment
PEGylates B-glucocerebroside
what enzyme is missing in Fabry
what disease did gene therapy work for
SCIDS (IL-2 receptor def)... Both ADA SCID and X-SCID
what do the vectors have that is needed
regulatory elements and LTR (long terminal repeats) help.
in vivo vs ex vivo
in vivd attempts to modify the cells within us. Ex-vivo attempts to take our cells, culture them and clone into them, then put back into us
totipotant vs pluripotant SCs
totipotant into any tissue. plurioproant into an embryonic tissue (more limited)
strategy for embryonic stem cell gene therapy
take the patients cells. genetically correct it. put it into an enucleated egg. wait for it to grow and take its stem cells. turn it into the correct tissue. then transfer back in
what is the alternative to embryonic stem cells
induced pluripotent stem cells
what are iPSCs
adult cells reprogrammed to go back to an embryonic-like state
miRNA/siRNA relation
miRNA processed into siRNA. they regulate mRNA stability.
name the four classical single gene disorders
DMD, CF, OI, alpha-1 TD
DMD is what pattern of inheritance
X-linked recessive
caveat to DMD POI
1/3 of the people are new spontaneous mutations
DMD genetic fitness
0. don't die early but just can't reproduce
when do you get DMD and when becked MD
becker is less severe. usually the mutation is in frame
why can DMD be tough to test for
1/3 are spontaneous and many others are from small changes...not large deletions
how can women sometimes get DMD
functional mosaicism due to skewed X-inactivation
5 ways to get CF; class I
mRNA issue. nonsense mutation
class II
protien made but stays in ER. d508. most common type
class III, IV, V
III: protei to membrane. no fn. IV: reduced cl- flow. V: mRNA f'ed cause of promotor or splicing.
so most common one
class II. d508. ER trafficing issue
what is residual risk
risk that you are a carrier despite testing positive (lets say the test does not check all mutations)
CF tests 90% of possible mutations. you are negative. your brother has CF. what is the chance you are the carrier
2/3 x 1/10 = 2/30
OI a problem with
collagen maturation
OI and eyes
blue sclera
which type of OI (1-4) is lethal perinatal
normal structure of collagen
triple helix
two types of collagen to know and their genes
type I/alpha 1: COL1A1. Type I/alpha 2: COL1A2
composition of a normal collagen helix
two type 1's and one type 2
explain a dominant negative loss of fn mutation in relation to OI
in this case, losing one allele to mutation but having an ok other one is NOT enough. In OI, an abnormal allele for COLA1.
so is OI dominant or negative
generally, would be dominant
alpha-1 AT def caused by mutations to
SERPINA1 (makes AAT)
what does AAT do
inhibits many proteases
specifically inhibits what enzyme
neutrophil elastase
def of what allele causes most AATD
Z allele (ZZ is the worst)
what happens to the protein with a defective Z allele
protien made, aggregates in liver where its made, causes liver cirrhosis
smoking an AAT
smoking can cause oxidization of methionine 358. so enzyme is less effective...think COPD
auto recessive. cause hetero still has enough normal fn'ing
what chromosome are the alpha globin genes on
ch 16
how many alpha globin genes are there
4, 2 genes and 2 alleles
what chromosome is b-globin on
ch 11
how many b-globin proteins are there
2 (1 gene)
a, b, y. which is where throughout life
a always there. y at birth but at 1 year drops and b replaces it
HbA seen when, and composition
adult. 2 alpha 2 beta
HbF seen where
in fetal. 2 alpha and 2 gamma
a qualitative change to globins is called a
a quantitative change in globins is called a
HbS is what
sickle cell
where is the mutation in SCA
b globin, Glu to Val at position 6
auto rec
SCA problem on whar chromsome
ch 11 (beta)
no produciton of which Hb
what happens at a sickling crisus
they aggregate and get stuck occluding a vessel
good idea for treatment of SCA
demethylate fetal hemoglobin
phenotype of hetero sickle guy designated
is it dangerous
nope, its benign, but problems at low oxygen saturation (excercise, deep sea diving)
other than HbS, whats another type of hemoglobin mutation
mutationin HbC
missense at pos 6 of B globin gene. Glu to Lys
HbC characteristics
lower solubility like S. tend to crystallize in RBCs. similar to HbS
thalassemias are a problem with what
synthesis (quantitiative) of globin chain
which is more severe, a or b thalassemia
a is more severe
what can cause alpha thalassemia genetically
unequal crossing over during homologous recombination
what is cis a-thalassemia
we have 4 alpha globin genes. Lose 2 on the same allele
what is trans a-thalassemia
2 KO alpha genes on differetnt homologs
which is more dangerous, cis or trans and why
cis is. severe for next generation. 2 cis parents come together kid is f'ed
2 cis parents make a kid with what
Hemoglobin bart hydrops fatalis
problem with Hb Bart
no alpha at all. baby dies neonatal
HbH is what
3 alpha KO'd, only one fn'ing. sucks but can live
cis and trans parents mate to make
HbH (2 alphas gone)
cis and cis mate to make
hydrops fatalis baby
B thalassemia POI
auto recessive
what is the problem with having no betas
excessive alphas lose solubulity, precipitate and lead to hemolytic anemia
two types of b thalassemia interms of damage to beta
b+ is reduced gene expression. bo is complete suppression of expression
3 manifests of actual disease
B thalasemia major is two damages alleles. B thal intermedia is one. B thal minor is carrier
treatment for b thalassemia.
bone marrow transplant. also can do transfucions
Hemophelia A is a def of
factor 8
POI of Hemo A
Hemo B is a def in
factor 9
Hemo A maon mutation type on actual DNA
x recessive male to male
why can some women carriers of hemo get synptoms
skewwed x inactivation
targeted screening vs pop screening
targeted is screening groups to be at risk
examples of population screenign
prenatal screening for all preg moms. Neoanatal screening
when can you do maternal serum screening
16 weeks
when can you do ultrasounds
18 weeks
when can you do amniocentisis
16 weeks
when can you do chorionic villus sampling
10-12 weeks
which are invasive
amnio and CVS
maternal serum sees hgih AFP, meaning
Neural tube defect
other diease from serum, triple test
downs synd
triple test shows
low AFP, low uncong estriol, high human chorionic gonadotropin hCG.
if downs syndrome, what else is seen in blood
fetal chromsome 21 fragments in blood
what if you have low AFp, low hCG, and low estradion
edwards syndrome, trisomy 18
ultrasounds can detect
neural tube defects
how can an ultrasound check edwards syndrome
rock bottom foot
how can ultrasounds detect cri0du-chat
micrognathia (small jaw)
how to do chorionic villus sampling
10-12 weeks, remove fetal cells by aspiration from placenta through vag
why do CVS
can do fish
how to do amniocentesis
needle transabdominally. get fetal cells. pellet them save supernatant
sup and pellet used for
sup for AFP assay. pellet for chromsome checks
when can artificial repro tech come in handy aside from infertility
do in vitro. check embryo for problem like CF or DMD, then implant
how to check PKU
automated fluorometric assay. also chek elevated levels of Phe in circulation via bacterial inhibition test
how to check CF
immunoreactive trypsin and DNA analysis, also check d508, and sweat chloride test
how to check SCA
hemoglobin electrophoresis, also ASO of DNA
how to check thalassemia
also hemoglobin electrophoresis
what is residual risk
tests negative, but left over % of unchecked possible ways to get disease
informed choice vs informed consent
choice: full choices of options available must be known. and consqueneves....Consent: consent after knowing all possibilities
what are pharmacogenomics
the study of the role of inheritance in variation in drug response
3 types of genetics cariation that can influcnce the drug action
1) pharmacokinetics (variation in proteins involved in drug metabolsm). 2) pharmacodynamics (variation of drug targets). 3) proteins involved in adverse effects of the drug
p-kinetics vs dynamics.
kinetics is ADE (absorption, distribution, elimination). Dynamics is effect at action site.
genetic polymorphisms to enzymes that break down the drugs are kinetics or dynamics
Butyrycholinesterase polymorphism affects
these are NMJ blockers used during surgery for muscle paralysis
butyrycholinesterase metabolizes what
defect in BCHE results in
prolonged paralysis cause SC not broken down quick enough
N-acetyltransferase dows what
catalyzes the acetylation of isoniazid
diff people's reactions to isonazid metabilosm puts them in two categories
slow acetylators and fast acetylators
slow acetylators have genetically what pattern for the NAT2 gene
homozygous for auto recessive
problem with slow acetylators
prone to toxicity of the drugs that are metabolized by acetylation
CYP2D6 polymorphism, CYPD6 is what sort of protein
cytochrome p450 family
poor CYP2D6 metabolizers have what gene pattern
homozy for auto recessive
strong CYP2D6 have what gene pattern
homozygous for WT
drugs CYP2D6 breaks dwon
metoprolol, haloperidol, codeine, impirine (beta blockers, antipsychotics, opiods, antidepressants)
what pain reliever won't work in CYP2D6 poor people and why
codeine won't work. CYP2D6 turns codeine into its effective form morphine
why is codeine dangerous with ultra rapid metabolizers
need a higher dose but can overdose
last of the four drugs to know
thiopurine S-methyltransferase
what does TPMT do
methylates the anti-cancer drugs
how to ID the anti-cancer drugs
they end in purine/prine. 6-mercaptopurine and azathioprine.
what does methylation do to them
inactivates them.
so if you are auto rec for the polymorphism, how to treat your cancer
give low doses
what makes warfarin whacky in terms of PD and PK
warfarin is racemic. R/S which are metabolized diff by diff enzymes
R or S warfarin is more potent
what metabolizes S
so the CYP 2C9 polym's is PK or PD
what is the PD componant to warfarin that is diff in people
its molecular target is Vit K epoxide reducatse
what does warfarin do with vitK reducatase
inhibits it, so no clotting factor made
so where is the PD polymorphism
we have diff strengths to our Vit K reducatase, requiring more or less warfarin
idiosyncratic drug effects deal with what
not the drug metabolism or target, they deal with a unique aspect of the individuals person physiology
give an example of an idiosyncratic drug effect
some people with G6PD def cannot take anti-malarials
what does G6PD do
keeps a reduced glutatione pool to protect RBCs from oxidative damage
whats the deal with G6PD def and drugs
antimalarials or fava beans or anything that makes oxidative stress is bad for these people
malignant hypothernia POI
autosomal dominant!
what us malignant hypothermia
die when we are given anesthitics
what drugs can cause it
halothane or succunylcholine
what is the molecular defect in malignant hyperthermia
altered ca+ control cause of defect in ryanodine recetpro gene. Massive release of ca++ unregulated
what causes the heat production
huge ca++ release, leads to muslce acitivty an ATP use
how to test for the potential problem
caffiene-halothane test
explain the test
remove some muscle, electricity it, shoulds see normal contractions. Then add caffiene. see similar effects.