Term
|
Definition
| neither allele is dominant - seen in blood groups: A, B, AB, etc |
|
|
Term
| what is variable expression? |
|
Definition
| nature and severity of phenotype vary from 1 individual to another. neurofibromatosis type 1 pts have varying severity. |
|
|
Term
| what is incomplete penetrance? |
|
Definition
| not all individuals w/a mutant genotype show the mutant phenotype |
|
|
Term
|
Definition
| 1 gene has > 1 effect on an individual's phenotype. PKU causes many seemingly unrelated symptoms, ranging from mental retardation to hair/skin changes. |
|
|
Term
|
Definition
| differences in the phenotype depend on whether the mutation is of maternal/paternal origin. prader willi (deletion of Paternal chr 15 gene = mental retardation, hyperphagia, obesity, hypogonadism, and hypotonia) and angelman's (deletion of maternal chr 15 gene = mental retardation, seizures, ataxia, inappropriate laughter [happy puppet]) are examples |
|
|
Term
|
Definition
| the severity of disease worsens or age of onset of disease is earlier in succeeding generations. huntington's is an example. |
|
|
Term
| what is loss of heterozygosity? |
|
Definition
| this can occur with Rb, where the pt inherits or develops a mutation - but the complementary allele must be deleted/mutated before CA develops. this is not true of oncogenes. |
|
|
Term
| what is dominant negative mutation? |
|
Definition
| a heterozygote produces a nonfunctional altered protein that also prevents the normal gene product from functioning. |
|
|
Term
| what is linkage disequilibrium? |
|
Definition
| a tendency for certain alleles at 2 linked loci to occur together more often than expected by change. this is measured in a population, not a family. |
|
|
Term
|
Definition
| this occur when cells in the body have a different genetic makeup. can be germ-line - which would produce disease not carried by the parent somatic cells. lyonization is an example of this. |
|
|
Term
| what is locus heterogeneity? |
|
Definition
| mutations at different loci which can produce the same phenotype. marfans, MEN 2B, and homocystinuria all cause the marfan's habitus. albinism is also an example. |
|
|
Term
|
Definition
| presence of both normal and mutated mtDNA = variable expression in mitochondrial inherited disease |
|
|
Term
| what is uniparental disomy? |
|
Definition
| offspring receives 2 copies of a chromosome from 1 parent and none from the other. |
|
|
Term
| what are hardy-weinberg population genetics? |
|
Definition
| p and q are separate alleles. disease prevalence: p^2 + 2pq +q^2 = 1. allele prevalence: p + q = 1. 2pq = heterozygote prevalence. the prevalance of X-linked recessive disease in males = q and q^2 in females. this assumes: no mutation occurring at the the locus, no selection for any of the genotypes at the locus, completely random mating and no migration. |
|
|
Term
| what is crucial to the dx of autosomal dominant disease? |
|
Definition
| fam hx. autosomal dominant: often plieotrophic and in many cases - presents after puberty. |
|
|
Term
| when do pts w/autosomal recessive disease generally present? |
|
Definition
| childhood. often more severe. |
|
|
Term
| can heterozygous females be affected by X-linked recessive disorders? |
|
Definition
|
|
Term
| what kind of inheritance is hypophosphatemic rickets (vit D resistant, increased phosphate wasting @ proximal tubule)? |
|
Definition
| X-linked dominant - of which all female offspring of the affected father are affected. |
|
|
Term
| what characterizes mitochondrial inheritance? |
|
Definition
| this is only transmitted through the mother and results in variable expression in the population due to heteroplasmy. mitochondrial myopathies and leber's hereditary optic neuropathy (degeneration of retinal ganglion cells/axons = acute loss of central vision) are examples |
|
|
Term
| what characterizes the autosomal dominant disease achondroplasia? |
|
Definition
| this is a cell signaling defect of *FGF receptor 3 and results in: dwarfism, short limbs - but head and trunk are normal size. associated w/advanced paternal age. |
|
|
Term
| what characterizes autosomal dominant polycystic kidney disease? |
|
Definition
| this is *always bilateral, involves massive enlargement of the kidneys due to multiple large cysts. pts present w/flank pain, hematuria, HTN, and progressive renal failure. 90% of cases are due to mutations in APKD1 on chr 16 (16 letters in polycystic kidney). it is associated w/polycystic liver disease, berry aneurysms, and mitral valve prolapse. |
|
|
Term
| what characterizes the autosomal dominant disease familial adenomatous polyposis? |
|
Definition
| after puberty: the colon becomes covered w/adenomatous polyps. progresses to colon CA unless resected. due to a deletion on chr 5 (APC gene, 5 letters in polyp). |
|
|
Term
| what characterizes the autosomal dominant disease familial hypercholesterolemia? |
|
Definition
| elevated LDL due to defective or absent LDL receptor. heterozygotes: cholesterol ~ 300 mg/dl. homozygotes: 700+, severe atheroscleorotic disease early in life, and tendon xanthomas. MI may develop before age 20. |
|
|
Term
| what characterizes the autosomal dominant disease hereditary hemorrhagic telangiectasia (osler weber rendu)? |
|
Definition
| this inherited disorder of blood vessels leads to telangiectasia, recurrent epistaxis, skin discolorations, and AVMs. |
|
|
Term
| what characterizes the autosomal dominant disease hereditary spherocytosis? |
|
Definition
| spheriod erythrocytes due to spectrin or ankyrin defect resulting in hemolytic anemia and increased MCHC. splenectomy is curative. |
|
|
Term
| what characterizes the autosomal dominant disease huntington's disease? |
|
Definition
| depression, progressive dementia, choreiform movements, caudate atrophy, and decreased levels of GABA/ACh in the brain. symptoms manifest between 20-50 y/o. gene located on chr 4 (hunting 4 food). CAG repeats. |
|
|
Term
| what characterizes the autosomal dominant disease marfan's syndrome? |
|
Definition
| a fibrillin gene mutation = connective tissue disorder affecting the skeleton, heart, and eyes. pts have long extremities, pectus excavatum, hyperextensive joints, long tapering fingers/toes, cystic medial necrosis of the aorta -> aortic incompetence and dissecting aortic aneurysms/floppy mitral valve. subluxation of the lenses. |
|
|
Term
| what characterizes the autosomal dominant disease multiple endocrine neoplasias (MEN)? |
|
Definition
| syndromes 1, 2A/B are characterized by familial tumors of endocrine glands - including those of the pancreas, parathyroid, pituitary, thyroid and adrenal medulla. MEN 2A/B are associated w/ the ret gene. |
|
|
Term
| what characterizes the autosomal dominant disease neurofibromatosis type I? |
|
Definition
| cafe au lait spots, neural tumors, lisch nodules, skeletal disorders (scoliosis) and optic pathway gliomas. chr 17. |
|
|
Term
| what characterizes the autosomal dominant disease neurofibromatosis type II? |
|
Definition
| bilateral acoustic schwannomas, juvenile cataracts, chr 22. |
|
|
Term
| what characterizes the autosomal dominant disease tuberous sclerosis?? |
|
Definition
| facial lesions (adenoma sebaceum), hypopigmented "ash leaf" spots on skin, cortical/retinal hamartomas, seizures, mental retardation, renal cysts, renal angiomyolipomas, cardiac rhabdomyomas, increased incidence of astrocytomas. incomplete penetrance/variable presentation. |
|
|
Term
| what characterizes the autosomal dominant disease von hippel-lindau disease? |
|
Definition
| hemangioblastomas of retina/cerebellum/medulla, about half affected pts develop multiple bilateral renal cell CA and other tumors. associated w/deletion of the VHL gene (tumor suppressor) on chr 3 (VHL = 3 words) |
|
|
Term
| what are the autosomal recessive diseases? |
|
Definition
| albinism, ARPKD, cystic fibrosis, glycogen storage diseases, hemochromatosis, mucopolysaccharidoses, phenylketonuria, sickle cell anemias, sphingolipidoses, and thalassemias. |
|
|
Term
| what characterizes cystic fibrosis? |
|
Definition
| defect on the CFTR gene on chr 7 (commonly Phe 508 deletion) leading to abnormal protein folding and thus degradation of the Cl- channel (which actively secretes Cl- in lungs/GI and resorbs from sweat). this leads to recurrent pulmonary infections (pseudomonas/s. aureus), chronic bronchitis, bronchiectasis, pancreatic insufficiency (malabsorption/steatorrhea), and meconinum ileus in newborns. males are infertile. fat soluble vitamins: KADE are deficient. increased Cl- in sweat test is diagnostic. tx: N-acetylcysteine - loosens mucus plugs. |
|
|
Term
| what is the mnemonic for the X-linked recessive disorders? |
|
Definition
| Be Wise, Fool's GOLD Heeds Silly Hope. Brutons agammaglobinemia, Wiskott-Aldrich syndrome, Fabry's disease, G6PD deficiency, Ocular albinism, Lesh-Nyhan syndrome, Duchenne's muscular dystrophy (and Becker's), Hunter's Syndrome, and Hemophila A/B. |
|
|
Term
| what characterizes the X-linked recessive disorder's duchenne's muscular dystrophy? |
|
Definition
| Duchenne's = Deleted Dystrophin (DMD - helps anchor muscle fibers). this is an X-linked frameshift mutation. weakness begins in the pelvic girdle muscles and progresses superiorly. pseudohypertrophy of calf muscles due to fibrofatty replacement of muscle and cardiac myopathy. use of gower's maneuver to stand up is characteristic. onset before 5 yrs. dx: increased CPK+muscle bx. |
|
|
Term
| what characterizes the X-linked recessive disorder's becker's muscular dystrophy? |
|
Definition
| same as duchenne's, but less severe. presents in adolescence/early adulthood. dx: increased CPK+muscle bx. |
|
|
Term
| what characterizes fragile X syndrome? |
|
Definition
| this X-linked defect affects the methylation and expression of the FMR1 gene. chr breakage is associated. 2nd most common cause of genetic mental retardation after downs. pts present w/macro-orchidism, long face w/large jaw, large everted ears, autism and mitral valve prolapse. fragile X = eXtra large testes/jaw/ears. trinucleotide repeat disorder: CGC. |
|
|
Term
| what are the trinucleotide repeat expansion diseases? |
|
Definition
| huntington's disease (CAG), myoTonic dystrophy (CTG), friedreich's ataxia (GAA), and fragile X syndrome (CGG). try hunting for my fried eggs. |
|
|
Term
| what characterizes down syndrome? |
|
Definition
| trisomy 21. pts present with: mental retardation (most common cause), flat faces, prominent epicanthal folds, simian crease, gap between 1+2 toes, duodenal atresia, congenital heart disease (commonly septum primum type ASD). associated w/risk of ALL and alzhiemer's disease. 95% of cases due to meiotic nondisjunction of homologous chromosomes. results of pregnancy quad screen: decreased alpha fetoprotein, increased beta-hCG, decreased estriol, and increased inhibin A. US shows increased nuchal translucency. |
|
|
Term
| what characterizes down syndrome? |
|
Definition
| trisomy 18 (election age: 18). pts present w/severe mental retardation, rocker-bottom feet, micrognathia, low set ears, clenched hands, prominent occiput, and congenital heart disease (death usually occurs w/in 1 yr of birth. most common live trisomy after down's. |
|
|
Term
| what characterizes patau's syndrome? |
|
Definition
| trisomy 13 (puberty). pts present w/severe mental retardation, rocker bottom feet, micropthalmia, microcephaly, cleft lip/palate, holoprosencephaly, polydactyky, and congenital heart disease. death usually occurs w/in 1 yr of birth. |
|
|
Term
| what is robertsonian translocation? |
|
Definition
| one of the most common types of translocation - usually involves 13, 14, 15, 21, and 22. occurs when the long arms of 2 acrocentric chromosomes fuse at the centromere and the 2 short arms are lost. balanced translocations normally do not cause any abnormal phenotype, unbalanced can resultin miscarriage, stillbirth, and chromosomal imbalance (down's etc). |
|
|
Term
| what is cri-du-chat syndrome? |
|
Definition
| congenital microdeletion of the short arm of chromosome 5. pts present w/microcephaly, moderate to severe mental retardation, high-pitched crying/mewing, epicanthal folds, and cardiac abnormalities. |
|
|
Term
| what is williams syndrome? |
|
Definition
| congenital microdeletion of chr 7 (includes elastin gene). pts present with elfin faces, mental retardation, hypercalcemia (increased vit D sensitivity), well-developed verbal skills, extreme friendliness w/strangers, and cardiovascular problems. |
|
|
Term
| what are the 22q11 deletion syndromes? |
|
Definition
| CATCH-22: Cleft palate, Abnormal facies, Thymic aplasia (T cell deficiency), Cardiac defects, Hypocalcemia (2' to parathyroid aplasia) - due to chr 22. *DiGeorge syndrome - thymic, parathyroid and cardiac effects. *Velocardiofacial syndrome - palate, facial and cardiac defects. |
|
|
