genetics Flashcards
describe electrical pathway of hear
SA in upper RA to AV in base of RA to Bundle of His in upper inter-ventricular septum down right and left bundle branches to their respective purkinje conduction pathways
purkinje, atrial muscle, ventricular muscle, AV node =
fastest to slowest conduction in heart
“Park at Venture Avenue”
fastest to slowest conduction in heart: purkinje fiber, atria, ventricle muscle, AV node)
bone side effect of corticosteroids
avascular necrosis
avascular necrosis XR finding
crescent sign, which indicates subchondral collapse
osteoarthritis XR findings
osteophytes and joint space narrowing
does osteoarthritis typically respond to OTC anaelgesics?
YES
what are the four bone diseases of renal osteodystrophy
hyperparathyroid bone disease, osteomalacia, mixed uremic osteodystrophy, and aplastic bone
osteopetrosis
inherited, bones become harder and more dense
paget’s disease
associated with osteosarcoma
substernal goiter
one or both thyroid lobes grow into the thoracic cavity inlet
explain the inflammatory process of gout crystals
normally have protective coating of apoE or B, but when exposed bare, become bound by IgG and inflammatory cells recruited
characteristic features of an arthritic joint
degeneration of articular cartilage, narrowing of joint space, bony outgrowths (osteophytes) at articular margins
endometriosis diagnosis?
NSAIDs for pain, hormonal contraceptives to control stimulation of tissue, and eventually possibly a laparoscopy for definitive diagnosis
leiomyomas
benign smooth muscle tumors characterized by a whorled pattern of smooth muscle bundles with intervening connective tissue
what is first-line medication for nausea and vomiting in pregnancy
B6/pyridoxine
vitamin A (retinol) terratogenic effects
microcephaly, cardiac anomalies, early epiphyseal closure, growth retardation, and spontaneous abortion
how can oseltamivir (tamiflu) shorten the course of influenza A and B infections when taken within 48 hrs of symptom onset?
inhibits neuramindases - normally the enzyme functions to cleave and release virions from infected cells so they can spread; results = accumulation of viral aggregates that are unable to infect new cells
influenza sx
fever, nonproductive cough, myalgias, clear lungs
ribavirin
inhibits viral RNA polymerase activity and RNA fragment initation and elongation; used in chronic HCV
BCL2
anti-apoptotic protein
what’s a way that follicular B cell lymphomas evade the immune system?
t(14;18) translocation that leads to BCL2 overexpression
this drug can be used to support diagnosis of the myasthnia gravis (Tensilon test)
edrophonium
location of M1
brain
location of M2
heart
location of M3
peripheral vasculature, lung, bladder, eyes, GI, skin
stimulation of M3
vasodilation, bronchoconstriction, contraction of detrusor muscle, miosis and accomodation, increased peristalsis and salivary and gastric secretions, increased sweat production
quaternary amine indirect cholinomimetics that CANNOT cross the BBB
edrophonium, neostigmine, pyridostigmine
cholinomimetics used for alzheimers
donepezil, galantamine, rivastigmine
atropine OD tx
physostigmine
heroine OD
CNS depression, seizures, pinpoint pupils
genetic polymorphism
gene exists in many forms (many alleles)
germ line mutation
mutation of sperm/egg; transmitted to offspring; every cell of body
somatic mutation
not inherited but in all daughter cells of mutated cell
co-dominance
both alleles contribute to phenotype; example = ABO blood types, for example AB express both A and B antigens
AAT gene
a-1-antitrypsin; co dominance determines level of protein
incomplete penetrance
not all patients with genotype will display disease features, often applied to AD disease; for example BRCA1 and BRCA2
expressivity
variations in phenotype; good example = NF1 (100% penetrance but symptoms vary loads)
pleiotropy
one gene = multiple phenotypic effects and traits; PKU, CF , marfan syndrome
tumor suppressor genes
gate keeper, DNA repair; requires both alleles to be lost to develop CA
classic example of two hit hypothesis for CA
retinoblastoma, HNPPC (Lynch Syndrome), FAP, Li Fraumeni; inherit one abnl copy through germline mutation then acquire another through somatic mutation
mosaicism
gene differences in cells of same individual; individual is mixture of different cells
somatic mosaicism
gene differences in tissues/organs; clinical phenotype varies depending on which tissue is affected
Mcune Albright Syndrome
only able to survive with somatic mosaicism
genetic heterogeneity
same phenotype from different genes/mutations (different mutation of same allele, different gene loci)
allelic heterogenity
multiple mutations of multiple alleles at same loci causing same disease
examples of allelic hetergeneity
beta thalassemia, CF
locus heterogeneity
mutations on different loci and different chromosomes
independent assortment
genes of homologous chromosomes will independently assort themselves
recombination frequency
increase with distance of genes on chromosome, can be used to determine relative gene locations
linkage
tendency of alleles to transmit together
linkage disequilibrium
population frequencies higher/lower than expected
linkage equilibrium
population frequencies
goal of meiosis I
reductive division = diploid to haploid = separates homologous chromosomes
aneuploidy
abnormal chromosome number
meiotic nondisjunction
failure of separation in either meiosis 1 or 2, will result in aneuploidy
meosis 1 nondisjunction
2 n with a chromosome from each mom and dad
trisomy 18
edward syndrome
trisomy 13
patau syndrome
why is advanced maternal age associated with increased risk of trisomy?
maternal meiosis NDJ error are a common cause - begins prenatally, completed at ovulation years later leaving LOTS of room for error to occur
robertsonian translocation
fusion of long arms of two chromosomes; occurs in chromosomes with centromere near end/acrocentric (13, 14, 21, 22)
complication of robertsonian translocation?
trisomy babies, many failed and spontaneously, terminated pregnancies
Hardy Weinberg Law
p + q = 1 ; p^2 + 2pq + q^2 = 1 ; p^2 is % of people in pop who are AA, 2pq is % of people in pop who are Aa
Hardy Weinberg Law assumptions
large population, completely random mating, no mutations, no migration in/out of population, no natural selection = allele frequencies do not change from one generation to the next
for very rare autosomal recessive diseases, what shortcut can be used to determine carrier frequency?
2q
give examples of autosomal dominant diseases
familial hypercholesterolemia, huntington’s disease, marfan syndrome, hereditary spherocytosis, achondroplasia
incomplete dominance
heterozygote phenotype different from homozygote; heterozygote less severe
incomplete dominance ex//
achondroplasia - heterozygote = dwarfism whereas homozygous is fatal
classic example of x-linked recessive
hemophelia A and B
lyonization
inactivated X chromosome resulting in a Barr Body in a female; random selection cell to cell; results in X mosaicism
classic example of x-linked dominant
fragile X syndrome
heteroplasmy
when there is a mixture of nl and abnl mtDNA in each cell
inheritance of mitochondrial DNA
from mother; if mom is homoplasmic then all children will have mutation, but if she has a mix of nl and abnl mtDNA (heteroplasmic) children inheritance is variable
polygenic inheritance
traits/diseases that depend on multiple genes; do not follow classic mendelian pattern
imprinting
epigenetic phenomenon that leads to different expression pattern than that of maternal/paternal genes
classic imprinting syndromes
Prader-Willi and Angelmann syndromes - 15q11-q13, paternal copy abnormal = prader-willi
prader-willi syndrome
loss of function of paternal copy of PWS gene on chromosome 15 and mother’s copy silenced by imprinting, resulting in complete suppression of PWS gene; obesity, hypotonia, hyperphagia and obesity, mild intellectual disability, delayed puberty
angelmann syndrome
loss of function of UBE3A on chromosome 15 and father’s turned off by imprinting, resulting in complete suppression of gene; happy, seizures, ataxia, severe intellectual disability
mosaicism
presence of multiple, genetically different cell lines within the body; can be classified as germline, somatic, or both; in germline mosaicism, the likelihood that future offspring will be affected by the same mutation depends on the proportion of mutant to wild-type germ cells in the mosaic parent
penetrance
probability that a person with a given mutant genotype will exhibit the corresponding phenotype
disorders of trinucleotide repeats
frequently demonstate anticipation
