Flashcards in Genetics Deck (85):
more than one phenotype for a given genetic mutation (ie PKU)
Difference in phenotype depend on whether mutation is maternal or paternal origin; Prader Willi and Angelman's syndromes
Dominant negative mutation
heterozygous mutation that exerts a dominant effect by producing a nonfunctional protein (ie. A nonfunctional transcription factor that still happens to bind DNA so acts to block wild type transcription factor) that prevents normal gene product from doing its job (another example is marfan's fibrillin mutation disrupts normal fibrillin)
When two alleles occur together more often than would be expected by chance alone.
Loss of genetic information during mitosis; Lyonization, Mutation in the embryonic precursor of the bone marrow stem cell
One phenotype from produced by different loci mutations; Marfan's syndrome, MEN 2B, albinism, homocystinuria
Presence of normal and mutated mtDNA results in variable expression of mito inherited disease
Offspring receive 2 copies from one parent and none from the other.
Normally inactivated maternal allele is active. Paternal allele is either deleted or abnormally silenced or has uniparental disomy from mother. Chr 15; Mental retardation, hyperphagia, obesity, hypogonadism, hypotonia
Normally inactivated paternal allele is active. Maternal allele is either deleted, inactivated, or uniparental disomy of father; Mental retardation, seizures, ataxia, inappropriate laughter
nondisjunction 47, XX, +13; arises during maternal meiosis I; Early defect in prechordal mesoderm development. Midface, eye, forebrain most affected: Cleft lip/palate, microphthalmia, microcephaly, holoprosencephaly, absent olfactory nerve, polydactyly, rocker-bottom feet, PDA, VSD, PCKD, Omphalocele or umbilical hernia
Causes of Down syndrome
Meitic nondisjunction of Chr 21 almost always of maternal origin; unbalanced robertsonian translocation where extra arm of chromosome 21 is attached to another chromosome; mosaicism where patients have a normal cell germ line and a trisomy germ line.
Hemophilia B/A Disorder's Inheritance is
Leber hereditary optic neuropathy inheritance
Burkitt's lymphoma; myc protooncogene is moved to 14 in front of immunoglobulin heavy chain.
Mantle cell lymphoma; Activation of cyclin D gene
Von Hippel-Lindau; autosomal dominant; medullary, cerebellar, and retinal hemangioblastomas; pheochromocytomas; pancreatic, hepatic, renal cysts; renal cell carcinoma
Fragile X gene
X-linked defect affecting methylation and expression of FMR1 gene. Trinucleotide repeat disorder of CGG resulting in hypermethylation of cytosine bases and gene inactivation
Cystic Fibrosis Mutation
Autosomal Recessive; Chromosome 7; deletion of Phe 508, mutation causes abnormal protein folding so it is degraded before even reaching the membrane. Normally the channel is activated by cAMP signaling and ATP gated
seen mostly in Turner's patients; tumor mostly located on neck and seen at birth. Swelling of the hands and feet is another manifestation. Swelling may decrease with age
lethargic, poor feeding, prolonged jaundice, constipation, hypotonia, pale cool skin, myxedema; Umbilical Hernia, increased risk of heart defects. T4 is essential for myelination
Trisomy 21 genetic abnormalities
Nondisjunction due to a failure of homologous chromosomes to separate in meiosis I or sister chromatids to separate during meiosis II.
eosinophilic intracytoplasmic inclusions in cortical neurons in Pick disease
inclusions that contain neurofilaments seen in neurons of substantia nigra in Parkinson
Conditions associated with Downs
AML, ALL, Parkinson, Hirschsprungs and Duodenal atresia
beta-amyloid accumulation in brain tissue and vessel walls.
Inhibition of gene expression in Huntington disease occurs via
CAG repeats lead to abnormal hintingtin protein which decreases the expression of other genes by inhibiting their transcription via hypermethylation of histones.
changes in genomic composition that occur when host cells are co-infected with two segented viruses that exchange whole genome segments. Can cause sudden alterations in the surface antigens of viral progeny
exchange of genes between two chromosomes (dsDNA) by crossing over within homologous regions.
uptake of naked DNA by prokaryotic or eukaryotic cell.
inhibition by one virus of the replication and or release of a second virus that is infecting the same cell.
G6PD deficiency inheritance
Follicular lymphoma, Bcl-2
ErbB2, HER2, neu
same name for epidermal growth factor receptor which is overexpressed in many booby cancers
vascular disorder characterized by facial port-wine stain and leptomeningeal angioma
chr. 17, autosomal dominant. Café au lait, neurofibromas, optic nerve gliomas, Lisch nodules, bony abnormalities; meningiomas, gliomas, pheochromocytomas.
Mitochondrial inheritable diseases
Leber Hereditary optic neuropathy -> bilateral vision loss; Myoclonic epilepsy with ragged-red fibers -> myoclonic seizures and myopathy associated with exercise; Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS)
Early-onset alzheimer disease
associated with APP (Chr 21) and Presenilin 1 and 2
Late-Onset alzheimer disease
Associated with apolipoprotein E4
Autosomal recessive microtubular defect
Tuberous Sclerosis inheritance
Friedrich's ataxia inheritance
failure of GnRH-secreting neurons to migrate from olfactory placode to hypothalamus; mutation in KAL-1 gene or FGF-Receptor 1 gene. Present with hypogonadism and anosmia, delayed puberty at presentation, Testes are small.
Xeroderma pigmentosa iheritance
DNA excision repair defect that is Autosomal Recessive
Klinefelter syndrome is inherited through
an extra sex chormosome acquired due to meiotic nondisjunction during gametogenesis. XXY
polygenic inheritance with variable penetrance.
Common conditions with polygenic inheritance
Androgenetic alopecia, epilepsy, ischemic heart disease, schizophrenia, glaucoma, HTN, malignancy, Type 2 DM
Cardiovascular associations with Downs, digeorge, Freidrich's ataxia, Marfan, and Tuberous sclerosis
Down: endocardial cushion defects; DiGeorge, ToF and interrupted aortic arch; Freidrich's ataxia, hypertrophic cardiomyopathy; Marfan, medial necrosis of aorta; Tuberous sclerosis, rhabdomyoma
AD, PKD1 [integral membrane protein, signal transducer; renal tubular development] mutation on Chr 16; berry aneurysms, mitrial valve prolapse
Familial adenomatous polyposis; Chromosome 5, APC gene (mismatch repair) Autosomal dominant
Familial hypercholesterolemia (IIA)
AD; defective or absent LDL receptor; high LDL; major atherosclerosis, xanthomas etc.
Osler-Weber-Rendu (Hereditary hemorrhagic telangiectasia)
AD; Blood vessel disorder with telangiectasia epistaxis, skin discoloration and AVMs
AD; spectrin or ankyrin defect; increased MCHC
AD; Chromosome 4; CAG
AD; 2A and 2B associated with Ret gene
chromosome 22; AD; mutation in merlin; bilateral acoustic schwannomas; juvenile cataract
von Hippel Lindeau
AD; deletion of VHL on Chr 3; constitutive expression of HIF that activates angiogenic growth factors
Glycogen storage diseases
AR (except Hunter's - X-linked)
AR (except Fabry's - X-linked)
Duchenne's and Becker's MD
Hemophilia a and b
13, 14, 15, 21, 22; long arms of two acrocentric chromosomes fuse at centromere. Can be balanced or cause trisomy