First Aid: Biochemistry 106-111 Day 1
Terms
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- nature and severity of the phenotype varies from 1 individual to another
- variable expression
- not all individuals with a mutant genotype show the mutant phenotype
- incomplete penetrance
- 1 gene has more than 1 effect on an individual's phenotype
- pleiotropy
- differences in phenotype depend on whether mutation is of maternal or paternal origin
- imprinting
- severity of disease worsens or age of onset of disease is earlier in succeeding generations
- anticipation
- mutation in tumor supressor gene, then complementary allele must be mutated before cancer develops
- loss of heterozygosity
- mutation that exerts a dominant effect; heterozygote produces nonfunctional altered protein that prevents normal gene product from functioning
- dominant negative mutation
- tendency for certain alleles at 2 linked loci to occur together; measured in a pop, not a family
- linkage disequilibrium
- occurs when cells in the body have different genetic makeup
- mosaicism
- random X inactivation in females
- lyonization
- mutations at different loci can produce the same phenotye (albinism)
- locus heterozygosity
- what is the heterozygote prevalence according to Hardy-Weinberg equilibrium
- 2pq (p,q are separate alleles)
- assumptions of Hardy-Weinberg
- no mutations, no selection, random mating, no migration
- modes of inheritance: due to defects in structural genes (often pleiotropic and presents after puberty)
- AD
- modes of inheritance: often due to enzyme deficiences (often presents in childhood)
- AR
- modes of inheritance: sons of heterozygous mothers have 50% chance of being affected (no male-to-male transmission)
- X-linked recessive
- modes of inheritance: either male or female offspring of affected mother may be affected, while all female offspring of affected father are diseased
- X-linked dominant (hypophosphatemic rickets)
- transmitted only through mother (may affect all offspring of affected females)
- mit inheritance (leber's hereditary optic neuropathy; mitochondrial myopathies)
- AD; always bilateral; massive enlargement of kidneys due to multiple large cysts
- ADPKD
- Presents with pain, hematuria, hypertension, progressive renal failure
- ADPKD
- What chromosome is the mutation in APKD1 on?
- chr 16
- What is APKD associated with?
- polycystic liver disease, berry aneurysms, mitral valve prolapse
- Stupid mnemonic for AD diseases: And Father Marfan Never kNew Timmy Von Hunt Forged His Acent
- ADPKD, Familial hypercholesterolemia, Marfan's syndrome, NF1, NF2, Tuberous Sclerosis, VHL dx, Huntington's dx, Familial adenomatous polyposis, hereditary spherocytosis, achrondroplasia
- elevated LDL owing to defective or absent LDL receptor
- familial hypercholesterolemia (hyperlipidemia type IIA)
- severe atherosclerotic disease early in life, tendon xanthomas (Achilles tendon), MI before age 20
- familial hypercholesterolemia (hyperlipidemia type IIA)
- fibrillin gene mutation
- Marfan's syndrome
- skeletal abnormalities: arachnodactyly, hyperextensive joints, and long, tapering fingers and toes
- Marfan's syndrome
- find dissecting aortic aneurysms and subluxation of lenses, along with skeletal abnl
- Marfan's syndrome
- cafe-au-lait spots, neural tumors, Lisch nodules (pigmented iris hamartomas).
- NF 1
- which chr for NF1?
- 17 (17 letters in Von Recklinghausen)
- bilateral acoustic neuroma, optic pathway gliomas, juvenile cataracts
- NF 2
- which chr for NF2?
- chr 22
- adenoma sebaceum, ash leaf spots on skin, cortical and retinal hamartomas, seizures, mental retardation, renal cysts, cardiac rhabdomyomas
- tuberous sclerosis
- hemangioblastomas of retinal/cerebellum/medulla, half get multiple bilateral renal cell ca
- VHL disease
- which chr for VHL disease?
- chr 3 (3 words)
- depression, progressive dementia, choreiform movements, caudate atropy, decreased GABA and Ach in brain, CAG repeats
- Huntington's dx
- Huntington's dx affects which chr
- chr 4
- colon becomes covered with adenomatous polyps after puberty
- familial adenomatous polyposis
- which chr for FAP
- chr 5 (5 letters in polyp)
- spheroid erythrocytes; hemolytic anemia; increased MCHC; splenectomy is curative
- hereditary spherocytosis
- defect in FGFR3
- Achondroplasia
- mnemonic for AR diseases: Crystal And Alfred Put Those Stupid Genes Inside My Stupid Horse
- cystic fibrosis, albinism, alpha-1-antitrypsin deficiency, phenylketonuria, thalassemias, sickle cell anemias, glycogen storage diseases, infant polycystic kidney disease, mucopolysaccharidoses (except Hunter's), spingolipidoses (except Fabry's), hemochromatosis
- AR defect in CFTR gene on chr 7
- Cystic fibrosis
- defective cl- channel, secretion of abnormally thick mucus that plugs lungs, pancreas, and liver
- cystic fibrosis
- recurrent pulmonary infections (Pseudomonas, s. aureus), chronic bronchitis, bronchiectasis, pancreatic insufficiency, meconium ileus in newborns
- cystic fibrosis
- diagnostic for CF
- increased concentration of cl- ions in sweat test
- most common lethal genetic disease of caucasians
- CF
- tx of CF
- N-acetylcysteine
- name 11 AR disorders (hint: FGHO; DHLFBW)
- Fragile X, G6PD deficiency, Hemophilia A and B, Ocular albinism, Duchenne Muscular dystrophy, hunter's syndrome, lesch-nyhan syndrome, fabry's disease, bruton's aggammaglobulinemia, wiskott-aldrich syndrome
- what gene is deleted in duchenne's md
- dystrophin (due to frameshift mutation)
- accelerated muscle breakdown, onset before 5, weakness begins in pelvic girdle muscles and progresses superiorly, pseudohypertrophy of calf muscles, Gowers' maneuver
- duchenne's muscular dystrophy
- dx of muscular dystrophies
- increased CPK, muscle biopsies
- name of disease where mutated dystrophin gene is less severe than duchenne's
- becker's
- defect in FMR1 gene, 2nd most common cause of genetic Mental retardation (behind Down's)
- Fragile X syndrome
- Associated with macro-orchidism, long face with large jaw, large everted ears, autism
- Fragile X syndrome (testes, jaws, ears)
- what is the triplet in Fragile X
- CGG
- Trinucleotide repeat expansion diseases
- Huntington's disease, myotonic dystrophy, friedreich's ataxia, fragile x (may show anticipation)
- 7 most common congenital malformations
- heart defects, hypospadias, cleft lip (w/ or w/o cleft palate), congenital hip dislocation, spina bifida, anencephaly, pyloric stenosis
- Name 3 autosomal trisomies; include chromosomes and prevalence
- Down's syndrome (trisomy 21, 1:700), Edward's syndrome (trisomy 18, 1:8000), Patau's syndrome (trisomy 13, 1:6000)
- most common chr d/o and cause of congenital mental retardation
- down's syndrome
- mental retardation, flat facial profile, prominent epicanthal folds, simian crease, duodenal atresia, congenital heart disease (most common is septum primum ASD due to endocardial cushion defects)
- Down's syndrome
- alzheimer's disease in affected people > 35 years old, increased risk of ALL
- Down's syndrome
- causes of Down's syndrome
- 95% due to meiotic nondisjunction of homologous chrs, 4% to robertsonian translocation, 1% to Down mosaicism (no maternal association)
- severe mental retardation, rocker bottom feet, low-set ears, micrognathia, congenital heart disease, clenched hands, prominent occiput. Death by 1 y.o.
- Edwards' syndrome
- severe mental retardation, microphthalmia, microcephaly, cleft lip/palate, abnormal forebrain structures, polydactyly, congenital heart disease, death by 1 y.o.
- patau's syndrome
- microcephaly, severe mental retardation, high-pitched crying/mewing, epicanthal folds, cardiac abnormalities
- cri-du-chat syndrome
- cri-du-chat syndrome is due to deletion of what?
- 5p
- 22q11 syndromes
- cleft palate, abnormal facies, thymic aplasia --> Tcell def, cardiac defects, hypocalcemia due to parathyroid aplasia
- when is highest risk of OH
- 3-8 weeks of pregnancy
- developmental retardation, microcephaly, facial abnormalities, limb dislocation, heart and lung fistulas
- fetal alcohol syndrome
- mechanism of fetal OH syndrome
- inhibition of cell migration
- number one cause of congenital malformations in US
- fetal OH syndrome