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68 Cards in this Set
- Front
- Back
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What type of expression
Blood groups A, B, AB |
codominant
neither of 2 alleles is dominant |
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What type of expression
2 patients with NF1 have varying degrees of severity |
Variable expression - nature/severity of phenotype differs amongst individuals
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What type of expression
Not all individuals with mutant genotype show mutant phenotype |
Incomplete penetrance
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What type of expression
PKU causes many seemingly unrelated symptoms (mental retardation to hair/skin changes) |
Pleiotropy
1 gene > 1 effect on phenotype |
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What type of expression
Prader Willi and Angelman's demonstrate what principle |
Imprinting = differences in the phenotype depend on whether the mutation is of maternal or paternal origin
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What type of expression
Huntington's disease - severity worsens/ age of onset is earlier in succeeding generations |
anticipation
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What type of expression
Retinoblastoma Need second hit after inheriting a mutation in a tumor suppressor gene |
Loss of heterozygosity
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Genetic terms
a mutation in Tx factor allosteric site leaves a nonfunctioning mutant that can still bind DNA and prevent wild-type Tx factor from binding |
dominant negative mutation
Heterozygote produces a nonfunctional altered protein that also prevents a normal gene product from functioning |
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Genetic terms
Tendency for certain alleles at 2 linked loci to occur together more often than expected by chance measured in a population, varies amongst populations |
linkage disequilibrium
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Genetic terms
Lyonization --> random inactivation of x in females --> cells in body have different genetic makeup what if in germ line? |
Mosaicism
germ line mosaicism --> produces disease that is not carried in parent's somatic cells |
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Genetic terms
Marfan's syndrome, MEN2B, and homocystinuria all cause marfanoid habitus; albinism |
Locus heterogeneity
mutations at different loci can produce same phenotype |
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Genetic terms
Presence of both normal and mutated mtDNA --> variable expression in mitochondrial inherited disease |
heteroplasmy
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Genetic terms
Offspring receives 2 copies of a chromosome from 1 parent, no copies from the other |
uniparental disomy
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Hardy Weinberg population genetics
4 assumptions |
1. No mutations at the locus
2. No selection for any genotypes 3. Completely random mating 4. No migration |
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Hardy Weinberg population genetics
alleles are p and q a. disease prevalence b. allele prevalence c. heterozygote prevalence d. x-linked recessive prevalence in males e. x-linked recessive in females |
a. p^2 + 2pq + q^2 = 1
b. p + q = 1 c. 2pq d. q e. q^2 |
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What is imprinting
What if the active allele is deleted |
At 1 locus, only 1 allele is active; the other allele is inactivated by imprinting/methylation
If active allele is deleted --> disease |
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Patient has
-mental retardation -hyperphagia -obesity -hypogonadism -hypotonia dx? genetics? |
Prader Willi
Deletion of normally active Paternal allele on chromosome 15 |
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patient has
-mental retardation -seizures -ataxia -inappropriate laughter (happy puppet) dx. genetics |
AngelMan's Syndrome
Deletion of normally active Maternal allele on chromosome 15 |
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Modes of inheritance
a. often due to defects in structural genes b. often due to enzyme deficiencies |
a. aut. dominant
b. aut. recessive |
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autosomal dominant vs. recessive
a. generations affected b. time of presentation c. severity of presentation |
a. dominant = many generations
recessive = 1 generation b. dominant = often after puberty recessive = childhood c. dominant = often pleiotropic recessive = more severe than dominant |
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Type of inheritance
sons of heterozygous moms have 50% chance of inheritance; no male to male transmission who can be affected by diseases that are transmitted like this |
x-linked recessive
males heterozygous females (less severe presentation) |
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Type of inheritance
Affected mom can transmit to either male or female offspring Affected dad will transmit to ALL female offspring |
x-linked dominant
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Child comes in with
-bone pain, weakness -bow-leggedness (genu varum) -rachitic rosary, deformed chest -lots of phosphate wasting at proximal tubule dx. genetics. |
hypophosphatemic rickets (aka vit D resistent rickets)
X-linked dominant |
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Type of inheritance
Transmitted only through mom, all offspring of affected females are affected |
Mitochondrial inhertance
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Mom has an acute loss of central vision due to degeneration of retinal ganglion cells and axons
all of her kids get the same condition all of her daughter's kids get the same condition dx. type of inheritance |
mitochondrial inheritance
Leber's hereditary optic neuropathy |
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Patient has short limbs, dwarfism, but a normal sized head
dx? genetics? defect? associated with what risk factor? |
Achondroplasia
aut. dom defect in FGFR3 advanced paternal age |
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Patient has
-flank pain, hematuria, HTN, renal failure -on imaging, you see bilateral, huge kidneys with cysts dx? genetics? 3 associated conditions? |
ADPKD
aut dom mutation in APKD1 (16) polycystic liver disease, berry aneurysm, mitral valve prolapse |
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Patient gets tons of adenomatous polyps after puberty
genetic defect? |
Familial adenomatous polyposis
aut dom. APC gene mutation (5) |
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Patient has atherscloerosis early in life, tendon xanthomas
cholesterol = 300 genetic defect? what if cholesterol = 700? risk of what? |
Familial hypercholestrolemia (hyperlipidemia IIA)
aut dom defect in LDL receptor --> high LDL if 300 --> heterozygote if 700 --> homozygote |
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2 conditions that result in MI before age 20
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familial hypercholesterolemia
hypertrophic cardiomyopathy |
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Pt has
-telangiectasias -recurrent epistaxis -skin discolorations -AVMs genetic defect? |
Hereditary hemorrhagic telangiectasia (osler weber rendu)
aut dom defect in blood vessels |
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Pt has hemolytic anemia and high MCHC
osmotic fragility test on RBCs positive dx? genetic defect? cure? |
hereditary spherocytosis
Aut dom defect in spectrin or ankyrin --> spheroid RBCs splenectomy |
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Pt has depression, progressive dementia, choreiform movements, caudate atrophy
-low GABA and ACh -pt is between 20-50 dx? genetic defect? |
Huntington's
au dom (CAG) repeat disorder in chromosome 4 |
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Pt has
-long lmbs, pectus excavatum, hyperextensive joints, long tapered fingers and toes genetic defect? what are the effects in the CV? |
Marfan's - aut dom defect in fibrillin
aorta: cystic medial necrosis --> aortic incompetence, dissecting aneurysms also mitral valve prolapse, Berry aneurysm, subluxation of lenses |
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MEN syndromes
genetics associated with mutation in which gene? |
aut dominant
MEN2A and 2B associated with ret gene mutation |
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Pt has
-cafe au lait spots -neural tumor -Lisch nodules -scoliosis -optic pathway gliomas dx? genetics? which chromosome? |
NF1 (von Recklinghausen)
aut dom mutation on chromosome 17q |
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pt has bilateral acoustic schwannomas, juvenile cataracts
dx? genetics? |
Neurofibromatosis type 2
aut dom defect on chromosome 22 |
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Pt has red papules on face, hypopigmented spots on skin, cortical and retinal hamartomas, siezures, MR, renal cysts
dx? genetics? 3 associated cancers? |
Tubersoous sclerosis
aut dominant angiomyolipoma, cardiac rhabdomyosarcoma, astrocytoma |
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pt has hemangioblastoma of retina/cerebellum/medulla
bilateral renal cell carcinomas, pheochromocytomas dx? genetic defect |
vHL disease
aut dom. defect in VHL tumor suppressor gene (3p) --> constitutive HIF expression and activation of angiogenic growth factors |
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type of genetic inheritance
Albinism |
AR
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type of genetic inheritance
infantile polycystic kindey disease |
AR
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type of genetic inheritance
CF |
AR
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type of genetic inheritance
glycogen storage diseases |
AR
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type of genetic inheritance
hemachromatosis |
AR
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type of genetic inheritance
mucopolysaccharidoses (except hunter's) |
AR
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what type of inheritance?
PKU |
AR
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what type of inheritance?
Sickle cell anemias |
AR
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what type of inheritance?
sphingolipidoses (except Fabry's) |
AR
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what type of inheritance?
thalassemias |
AR
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Pt is a child that secretes thick mucus that plugs lungs, pancreas and liver
gets chronic bronchitis, bornchiectasis, steatorrhea genetic defect? diagnostic test? treat? |
CF
aut recessive defect in CFTR gene (chrom 7, Phe 508) that codes for CFTR channel --> secretes Cl in lungs and GI, reabsorbs Cl from sweat dx: Cl sweat > 60mEq/mL N-acetylcysteine (cleaves disulfide bonds within mucous glycoproteins) + fat soluble vitamins + pancreatic enzyme replacement + antibiotics |
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biggest genetic killer of caucasians?
what infections does this condition make a patient susceptible to? |
CF (aut recessive)
pseudomonas and s. aureus pulmonary infections |
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2 causes of meconium ileus
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Hirschsprungs and CF
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9 x-linked recessive disorders
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Fabry's tale: Duke the Muscular Hunter Brutally Lysed the Albino Gopher without aWARe it was a Fragile Hemophiliac
Fabry's Duchennes (and BEckers) Hunter's Brutons agammaglobulinemia Lesch Nyhan Albinism (ocular) G6PD deficiency Wiskott-Aldrich Fragile X Hemophilia A and B |
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Patient is a 3 yo, has weakness in muscular girdle, progresses superiorly
-gets fibrofatty calves -uses gower's to stand up -high CPK dx? genetic defect? what makes this so prone to mutation? |
Duchenne's muscular dystrophy
x-linked frameshift mutation in DMD gene --> lack of dystrophin (which anchors muscle fibers) longest gene --> high rate of spontaneous mutation |
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Patient has proximal muscle weakness, fibrofatty calf muscles, and cardiac myopathy
-high CPK onset was early adulthood genetic defect |
x-linked mutation in dystrophin gene
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1st most common cause of genetic MR?
2nd? |
Down's
Fragile X |
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Pt has large jaw w/long face, long everted ears, autism, mitra valve prolapse, macroorchidism
dx? genetic defect? |
Fragile X
x-linked defect (CGG repeats) in the methylation and expression of the FMR1 gene --> FMRP gene dysfunction (involved in mRNA translation in axons and dendrites in brain and testes) |
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4 nucleotide repeat disorders
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"Tri HUNTING for MY FRIed eggs (x)"
Huntingtons (CAG) Myotonic dystrophy (CTG) FraGile x (CGG) Friedreich's ataxia (GAA) |
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Patient has MR, flat faces, epicannthal folds, simian crease, gap betwen first 2 toes, atresia, ASD
genetic defect? incidence? increases the risk of what 3 conditions? |
Downs - trisomy 21
-mostly meiotic nondysjunction, 4% robertsonian, 1% mosaicism 1:700 ALL, AML, Alzheimer's (>35yo) |
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Downs sydrome vs edwards
results of quad screen |
Downs: low aFP, high b-hCG, low estriol, high inhibin A
Edwards: same, but low b-hCG |
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Pt has
-MR -rocker bottom feet -micrognathia -low set ears -clenched hands -prominent occiput -congenital heart disease dx? genetic defect? incidence? |
Edwards
trisomy 18 (1:8000) |
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Pt has
-MR -rocker bottom feet -microphtalmia, microcephaly -celft lip/palate -holoprocesncephaly -polydactyly -congenital heart disease dx? genetics and incidence |
patau's
trisomy 13, 1:15000 |
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Balanced translocation that occurs when 2 acrocentric chromosomes fuse at the centromere and 2 short arms are lost
what are the chromosomes often affected |
robertsonian
13, 14, 15, 21, 22 |
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Pt has
-microcephaly -MR -high pitched crying -epicanthal folds -cardiac abnormalities dx? genetics |
Cri du chat
microdeletion of short arm of chrom 5 (46xx/xy, 5p-_ |
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Pt has elfin facies, MR, hypercalcemia, well-developed verbal skills, extreme friendliness with strangers, CV problems
dx? genetic defects? |
williams syndrome
microdeletion of long arm of chromosome 7 (includes elastin gene) |
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Cleft palate
Abnormal facies Thymic aplasia (T cell deficiency) Cardiac defects Hypocalcemia (parathyroid aplasia) where is the microdeletion? what is the embryological malformation |
22q11 deletion syndromes (DiGeorge and Velocardiofacial)
aberrant development of 3rd and 4th branchial pouches |
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22q11 microdeletion syndromes
thymic, PTH, and cardiac defects |
Digeorge
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22q11 microdeletion syndromes
palate, facial, cardiac defects |
velocardiofacial syndrome
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