genetics - modes of inheritance, etc Flashcards
x linked recessive diseases - 10
The OTc bitsy Hunter’s, name was Lesch Fabry,
he shot the Meinke, WASP and G6P,
up came Bruton, and what a Douchy guy,
A and B are xlinked… don’t forget DI
Ornithine Transcarbamylase Deficiency
Hunter's Lesch Nyhan Fabry Meinke Wiskott Aldrich WASP
Glucose 6 Phosphate Deydrogenase Deficiency G6P
Bruton’s Agammaglubulinemia
Duchenne’s muscular dystropy
haemophilia A and B
Diabetese Insipidus
Autosomal dominant disease?
row row row your boat
von von ALS
Rb MEN
Tubes &; Spheres & Huntingdon,
Marfan, Ehler’s Dan
Con, Con, Cholesterol, Osler-Weber-Rendu
Li-Fraumeni and Dystrophy, please include these two.
NF1 and 2, don’t FAP too much, autosomal dominant, yes this song is clutch
PLUS osteogenesis imperfecta,
achondroplasia
von Hippel, von Willebrand disease (most common) ALS (amyotropihic lateral sclerosis) Retinoblastoma MEN - Multiple Endocrine Neoplasia Tuberous Sclerosis Hereditary Sphereocytosis Huntingdon's Marfan's Ehler's danlos Con Con - Achondroplasia cholesterol - familial hypercholesterolemia Dystrophy - nyotonic muscular dystropy Neurofibromatosis Familiar Adenomatous Polyposis
Con Con - Achondroplasia
cholestero - familial hypercholesterolemia
Dystrophy - nyotonic muscular dystropy
autosomal recessive
cystic fibrosis - deficiency in the chloride channel CFTR 7
inborn errors of metabolism
PKU, von Gierke’s, Pompe’s, glycogen storage diseases, sphingolipidoses (except Fabry’s), and mucopolysaccharidoses (except Hunter’s)
sickle cell anemia thalassemias albinism ARPKD hemochromatosis
Lysosomal Storage Diseases
also - I (inclusion)-cell disease
Chédiak–Higashi syndrome
https://step1.medbullets.com/biochemistry/102080/lysosome
fabry gaucher tay sach's Niemann Pick Krabbe's Disease Hunter's Disease Hurtler's Disease
Metachromatic Leukodystrophy (no slide on this)
Fabry Disease?
“my Fabrite activity is Ceramics. We made a GalaXy”
enzyme: Alpha - Galactosidase A
Build up - Ceramide Trihexoside
Gaucher’s Disease
(in crying voice) “oh my Gauche, he’s such a Bro”
Enzyme: Glucocerebrosidase
Buildup : Glucocerebroside
in crying voice? because histology - Tissue Paper Cytoplasm
Tay Sach’s Disease
“A Gang of 6 small Jews”
Cherry red spot on Macula
Small ( no hepatosplenomegally associated) vs - Niemann Pick (also cherry red macula)
Enzyme: Hexosaminidase A
Buildup: GM2 glangioside
The macula provides us with the ability to read and see in great detail whereas the rest of the retina provides peripheral vision. Of all the different parts of the eye, the macula is where the most important images are created before being sent along the optic nerve to the brain, where vision is completed.
Niemann Pick
Pick your BIG nose with your Sphinger
hepatosplenomegally associated
Also in Ashkenazi jews - similar presentation to tay sach’s
cherry red macula
Enzyme: Spingomyelinase
Buildup: Spingomyelin
Krabbe disease
The KRABBE is out of this WORLD
histology - GLOBOID cells - always trying to get a big GLOB of crab meat when crack into the shell
Enzyme: Beta Galctocerebrosidase
Build up - Galactocerebroside
Hunter’s Disease vs Hurlers
X marks the spot
same build up to both
HurLer’s enzyme is L - iduronate
Enzyme: Iduronate Sulfatase
build up: Dermatan Sulfact
No corneal clouding in Hunters (put the gun up to your eye to shoot) need clear eyes - and gun is touching SKIN - Dermatan
Acid vs base - dirty medicine
https://www.youtube.com/watch?v=J9jisOXB_Oo
normal PH - 7.40
change in HCO3 - “metabolic”
change in CO2 - “respiratory”
PH= HCO3/CO2 = 24/40 = Metabolic / Respiratory
PH up - = Alkalosis
PH dn = Acidosis
memorizing amino acids -
https://www.youtube.com/watch?v=PmbcA1Sav7s
Inheritance Algorithm
https://step1.medbullets.com/biochemistry/102036/modes-of-inheritance
Great chart about inheritance
Does offspring with disease have a parent with disease? (Y/N) if YES dominant (does not skip generations) is there male-to-male transmission of disease? (Y/N) if YES autosomal dominant if NO do daughters of affected male have disease? (Y/N) if YES X-linked dominant if NO mitochondrial if NO recessive (can skip generations) predominantly males with disease? (Y/N) if YES X-linked recessive if NO autosomal recessive
mitochondrial mode of inheritance
passed down only through affected females to all their offspring regardless of the status of their mate most likely has a mitochondrial mode of inheritance. This pattern of inheritance is seen because mitochondria have a separate genome that is passed down from a mother to all her offspring.
Cystic fibrosis - autosomal recessive inheritance
Most commonly caused by a phenylalanine deletion at position 508 of the CFTR gene on chromosome 7.
elfin features?
Will Farrell - Williams Disease
Multifactorial inheritance diseases
7 common multifactorial genetic inheritance disorders heart disease, high blood pressure, Alzheimer's disease, arthritis, diabetes, cancer, and. obesity.
CLEFT LIP, Meningiocele, Coronary heart disease, Schizophrenia
Multifactorial inheritance means that “many factors” (multifactorial) are involved in causing a birth defect. The factors are usually both genetic and environmental, where a combination of genes from both parents, in addition to unknown environmental factors, produce the trait or condition.
if parents asked for chance of recurrence - would want to get info about how often this is occuring within particular family
Euploidy - normally Diploid 46, - Haploid 23occur normally - Triploid 69- can birth - die day one - (molar?) Tetriploid 92 (4x 23) never will birth
any multiple of correct amount
Molar pregnancy is an abnormal form of pregnancy in which a non-viable fertilized egg implants in the uterus and will fail to come to term. A molar pregnancy is a gestational trophoblastic disease which grows into a mass in the uterus that has swollen chorionic villi. These villi grow in clusters that resemble grapes.
Aneuploidy - any other combo than 45 or 47 will not surviv3
only 3 trisomies that can come to term - 13, 18, 21
when not a multiple of 23
Autosomal recessive disease
Oculocutaneous albinism, autosomal recessive polycystic kidney disease (ARPKD), cystic fibrosis, Friedreich ataxia, glycogen storage diseases, hemochromatosis, Kartagener syndrome, mucopolysaccharidoses (except Hunter syndrome), phenylketonuria, sickle cell anemia, sphingolipidoses (except Fabry disease), thalassemias, Wilson disease.
nucleoside vs. necleoTide (phosphaTe)
if no phosphaTe, it is a nucleoside
nucleoSide = base + Sugar
A nucleoside consists simply of a nucleobase (also termed a nitrogenous base) and a five-carbon sugar (ribose or 2’-deoxyribose) whereas a nucleotide is composed of a nucleobase, a five-carbon sugar, and one or more phosphate groups.
Why is RNA so labile?
While DNA contains deoxyribose, RNA contains ribose, characterised by the presence of the 2’-hydroxyl group on the pentose ring (Figure 5). This hydroxyl group make RNA less stable than DNA because it is more susceptible to hydrolysis. … Some viruses use RNA instead of DNA as their genetic material.
ribose vs. deoxyribose?
OH group at carbon 2 in ribose - H at 2 in DNA
where does phosphate bind?
where does Sugar bind?
PhosphaTe binds at 5, next nucleotide binds at 3
SUGAR
Purine: N9
Pyrimidine: N1
Sugars numbered by using Prime 1’, 2’ to avoid confusion with Carbons
Purines? PUre As Gold
two rings
GAG - 3 AA needed:
Glycine
Aspartate
Glutamine
two rings, larger, numbered counterclockwise
other purine metabolites - xanthind, hypsanthine, uric acid - (may be present in tRNA)
Deamination of Adenine - hypoxanthine
Deamination of Guanine - Xanthine
Adenine has Amino group - an NH2 group
Pyrimidines - CUT the PY
smaller - 6 atoms, numbered clockwise
thYmine has a methYl (see as CH3)
Deamination of cytosine = uracil
Methylation of uracil = thymine
A variety of different things can be made - various nucleoSides and Tides
Adenosine, Guanosine, etc (all nucleoSides)
AMP, ATP, GMP, etc - all have phosphaTe - nucleoTide
nucleoside triphosphates are used in synthesizing Nucleic Acids
when nucleotides polymerize to form nucleic acids - what happens?
ester bond formed, water produced - 3’ carb binds with phosphate on 5’ of other -
hence a phosphodiester bond -
free ends?
5’ phophate and 3’ free hydroxyl
nuclear envelope - found in prokaryotes or eudryotes?
only eukaryotes
Where is DNA found?
nucleus and mitochondria (less than 0.1%) - 20K base pairs vs 3 x 10 to the 9th - 3 billion in nucleus
When are chromosome visible?
during metaphase
axis of symmetry?
double helix - two chains are coiled around
backbone of sugar-phosphate on outside - hydrophobic bases inside
major (wider) and minor grooves - created access
some drugs sneak in thru the two grooves to stop creation of cancers, etc
cisplatin (bladder and lung) binds to DNA
Dactinomycin - intercalates in narrow groove - interferes w/ DNA/RNA synthesis??
What stabilizes helix?
hydrogen bonds (A - T 2, C - G 3) plus hydrophobic interaction of stacked bases
Chargoff’s rule -
In any DNA - amount of A = amount of T, and C % = G% - so if know one amount, can calculate all amounts
which bonds are more stable - A w/ T or C w/G?
C G - they have 3 bonds
how can denaturing occur?
heat, alkaline pH, chemicals such as formamide and urea
can be renatured if denaturing condition removed SLOWLY - important for Southern blot and polymerase chain reaction - process called hybridazation
different structural forms of double helix
antiparallel
complimentary
B, A, 2
B - right handed - 10 residues/360 (this is believed to be Chromosomal)
A right handed, 11 base pairs
2-DNA - left handed, 12 base pairs -
prokaryotic DNA?
single chromosome, w/ double stranded dna in circle (like mitochondria)
eukaryotic - 1000 x larger - continuous - not circular NEGATIVE charge - because of free phosphate - binding to equal weight of HISTONES
Histones - positive charge - made of?
Arginine and Lysine -
5 types of Histones
H1 (links) H2A H2B H3 H4
In the solenoid structure, 30nm
the nucleosomes fold up and are stacked, forming a helix. They are connected by bent linker DNA which positions sequential nucleosomes adjacent to one another in the helix. The nucleosomes are positioned with the histone H1 proteins facing toward the centre where they form a polymer.
packaging of DNA -
all together called Crhomatin - when extracted appear as beds on a string
beads are nucleosome cores,
beads with DNA protruding NUCLEOSOMES (10nm)
two molecule of each four core histone - form center - H1 is linker
packaged in solenoid structure 30nm
euchromatin?
transcriptionally active - looser, lighter colored
vs. heterochromatin -some heterochromatin becomes looser and is transcripted -
others - never does - IE Barr Bodies - (extra X in females - and in males with xxy - klinefelters)
histone acetylation?
vs underacetylation
occurs when more transcriptionally active -
underacetylation - where not active
bromodomain?
lysine acetylated in histone - more opens chromatin -
methylation? another histone modification
no direct correlation with opening or closing - active or inactive
some lead to more activation, others to less
what is a gene?
a complete sequence region leading to a functional product -
our DNA can create several million genes - but true number is 40,000 - 20 - 25,000 can be divided into four groups - genome maintenance, signal TBCONTINUED
base excision repair
GEL PLease -
What is spontaneous Deamination?
Spontaneous deamination is the hydrolysis reaction of cytosine into uracil, releasing ammonia in the process. … In DNA, this spontaneous deamination is corrected for by the removal of uracil (product of cytosine deamination and not part of DNA) by uracil-DNA glycosylase, generating an abasic (AP) site.
In single-strand DNA repair, in what phases of the cycle do nucleotide excision repair, base excision repair, and mismatch repair occur?
Nucleotide excision repair occurs in G1 phase of cell cycle; base excision repair, throughout cell cycle; mismatch repair, mainly in S phase
What enzyme category adds a hydroxyl group (-OH) to a substrate?
Hydroxylases (eg, tyrosine hydroxylase)
Which enzyme category relocates a functional group within a molecule?
mutases eg vitamin B12-dependent methylmalonyl-CoA mutase)
Which enzyme category catalyzes the transfer of a phosphate group from a high-energy molecule (eg, ATP) to a substrate?
Kinases
Which enzyme category joins 2 molecules together using a source of energy?
Synthase/synthetase (ATP, acetyl CoA, or a nucleotide sugar can be source of energy)
In what structures can reticulin be found?
Reticulin can be found in blood vessels, skin, the uterus, fetal tissue, and granulation tissue
Menkes syndrome
is a disorder that affects copper levels in the body. It is characterized by sparse, kinky hair; failure to gain weight and grow at the expected rate (failure to thrive); and deterioration of the nervous system.
A patient has autoantibodies against glomerular basement membrane. What type of collagen is most likely being targeted?
Type IV collagen (diagnosis: Goodpasture syndrome)
Which enzyme is responsible for covalently cross-linking lysine to hydroxylysine residues?
Lysyl oxidase (copper is required)
A defect in collagen cross-linking is implicated in which 2 diseases?
ehlers danlos, menkes
What is the role of heat shock proteins (eg, HSP60) in yeast?
They are chaperone proteins that are expressed at high temperatures to prevent protein denaturing/misfolding
What is the difference in function of myosin-light-chain kinase (MLCK) vs myosin-light-chain phosphatase (MLCP)?
K - contracts
P - Relaxes
Tensilon?
Tensilon is a readily reversible acetylcholinesterase inhibitor for myasthenia gravis
Neostigmine is an acetylcholinesterase inhibitor. Administration of this drug would increase the amount
of acetylcholine (ACh) present in the synapse and its ability to sufficiently depolarize the postsynaptic
membrane and trigger an action potential. Botulinum toxin antiserum is effective only against botulinum
toxicity. Curare blocks the nicotinic ACh receptor and causes muscle weakness. Atropine is a muscarinic
ACh receptor antagonist, and halothane is an anesthetic gas. Neither atropine nor halothane has any effect on the neuromuscular junction.
Botox, botulism
Botulinum and tetanus toxin are released from the same class of bacteria (Clostridium ).
blocks release of NT - maybe affects SNAREs
Botulinum toxin inhibits the release of acetylcholine from a -motoneurons by blocking one of the proteins responsible for the fusion of the synaptic channel with the presynaptic membrane.
Tetanus - blocks inhibitory NT
Tetanus toxin produces an increase in skeletal muscle contraction by blocking the release of inhibitory neurotransmitter from spinal interneurons.
Repetitive stimulation of a skeletal muscle fiber will cause an increase in contractile strength due to an increase in which of the following?
Select one:
a. The duration of cross-bridge cycling
Each time a skeletal muscle fiber is stimulated by an a motoneuron, enough Ca2+ is released from its sarcoplasmic reticulum to fully activate all the troponin within the muscle. Therefore, every cross bridge can contribute to the generation of tension. However, the transmission of force from the cross bridges to the tendon does not occur until the series elastic component (SEC) of the muscle is stretched. Repetitive firing increases the amount of SEC stretch by maintaining cross-bridge cycling for a longer period of time. Repetitive firing increases neither the concentration of Ca2+ within the myoplasm, the number of myofibrils that are activated, nor the magnitude of the end-plate potential. Because all of the cross bridges are activated each time a skeletal muscle fiber is activated, an increase in Ca2+ concentration would have no effect on muscle strength. Limitation in rising from a seated position or combing hair is suggestive of proximal muscle weakness, characteristic of dermatomyositis.
A 35-year-old woman is seen by a neurologist to evaluate her incapacitating muscle weakness. The neurologist suspects myasthenia gravis and decides to confirm his diagnosis by administering a drug that increases the force of muscle contraction in patients with myasthenia gravis. Caution is advised when administering the drug to patients with heart disease because bradycardia may develop. Which of the following most likely explains the ability of the drug to increase the force of muscle contraction in patients with myasthenia gravis?
The drug used to test for myasthenia gravis is an acetylcholine esterase inhibitor such as neostigmine. The drug prevents the breakdown of acetylcholine, increasing the duration of time acetylcholine remains in the synaptic cleft. Because acetylcholine can bind to the endplate receptors for a longer time, the magnitude of the end-plate potential increases, increasing the probability of it generating an action potential. The greater the action potential force rate, the greater the source of muscle contraction. Increasing the amount of acetylcholine released by the a motoneurons, by increasing the affinity of the skeletal muscle receptors for acetylcholine or increasing the discharge rate of a motoneurons could cause a similar effect. However, none of these changes would affect heart rate. The cautious use of this test in patients with heart failure results from the possibility that the decreased breakdown of acetylcholine released by the vagus nerve could decrease heart rate to dangerously low levels.
The correct answer is: Decreasing the metabolic breakdown rate of acetylcholine
The amount of force produced by a skeletal muscle can be increased by which of the following?
Select one:
a. Decreasing the interval between contractions
The shorter the interval between the contractions, the greater the summation will be. Maximum summation is called tetanus.
atropine
Parasympathetic stimulation or cholinergic muscarinic agonists used to treat glaucoma produce miosis, that is, pupillary constriction caused by contraction of the sphincter muscle of the iris. Anticholinergic agents (e.g., atropine) or sympathetic stimulation produce mydriasis, that is, pupillary dilation, in which the increase in pupil size results from contraction of the radial muscle of the iris mediated by a1-adrenergic receptors.
muscarinic poisoning.look for signs where Muscarine receptors are affects
Muscarine binds to acetyl- choline muscarinic receptors on cardiac and smooth muscle. These are the same receptors activated by the release of acetylcholine by the vagus nerve. Cardiac muscarinic receptors decrease the rate of phase 4 depolarization and therefore, decrease the heart rate. A heart rate less than 60 beats per minute is called bradycardia. Acetylcholine receptors on the skeletal mus- cle end plate are nicotinic receptors and do not respond to muscarine. Dilation of the pupils and hypertension are signs of sympathetic, not parasympathetic activity.
The correct answer is:
Bradycardia
b2 receptors?
Epinephrine (adrenalin) acts on both a- and b-adrenergic receptors, but has a greater affinity for b-adrenergic receptors. Activation of b2-adrenergic receptors leads to relaxation of smooth muscle in the bronchi, vasculature, intestine, uterus, and bladder, to increased pan- creatic insulin and glucagon secretion, and an increase in liver glycogenolysis. The bronchodilator effects of epinephrine are key in the treatment of the life- threatening effects of anaphylactic shock. Activation of b1- and b2-adrenergic receptors in the heart leads to an increase in the rate of SA nodal phase 4 depo- larization and thus heart rate (positive chronotropic response), an increase in contractility (positive inotropic response), an increase in conduction velocity (positive dromotropic response), and an increase in cardiac excitability/irri- tability. The transport of Ca2+ into skeletal muscle fibers is not affected by b receptors. The effects of epinephrine-induced b-adrenergic receptor activa- tion are due to G-protein mediated activation of adenylate cyclase, which catalyzes the formation of cyclic adenosine monophosphate (cAMP) and acti- vation of protein kinase A.
The correct answer is:
The contraction of airway smooth muscle
Cells of the adrenal medulla receive synaptic input from which of the following types of neurons?
Preganglionic sympathetic axons synapse on cells in the adrenal medulla that function as postganglionic sympathetic neurons.
Which substance activates adrenergic alpha and beta receptors equally well? Select one: a. Serotonin b. Norepinephrine c. Epinephrine d. Acetylcholine e. Dopamine
Epinephrine activates alpha and beta adrenergic receptors equally well.
Norepinephrine excites both types of receptors, but has a markedly greater effect on alpha receptors
control of systemic arterioles. Which of the following actions would lead to vasodilation of systemic arterioles?
Decreased activity of postganglionic sympathetic neurons leads to vasodilation of systemic arterioles. In contrast, increased activity in postganglionic sym- pathetics results in vasoconstriction.
A 66-year-old man with chronic hypertension is treated with prazosin by his physician. The treatment successfully decreases his blood pressure to within the normal range. What is the mechanism of the drug’s action?
Prazosin is a specific antagonist of α1 receptors, which are present in vascular smooth muscle, but not in the heart. Inhibition of α1 receptors results in vasodilation of the cutaneous and splanchnic vascular beds, decreased total peripheral resistance, and decreased blood pressure.
The correct answer is:
Inhibition of a1 receptors on vascular smooth muscle
Which autonomic receptor mediates an increase in heart rate?
Phenoxybenzamine decreases blood pressure by acting as an α1 receptor antagonist, thus decreasing intracellular IP3/Ca2+.
b1
Heart rate is increased by the stimulatory effect of norepineph- rine on β1 receptors in the sinoatrial (SA) node. There are also sympathetic β1 receptors in the heart that regulate contractility.
