Genetics Flashcards
Codominance
both alleles contribute to the phenotype
Variable Expressivity
Phenotype varies among individuals with the same phenotype
Incomplete Penetrance
Not all individuals with a specific genotype show the phenotype
Pleiotropy
One gene contributes to multiple phenotype effects
Anticipation
Increased severity or early onset of disease in succeeding generations
Dominant Negative Mutation
Heterozygote produces a nonfunctional altered protein that prevents the normal one form functioning
Linkage Disequilibrium
Tendency of alleles at linked loci to occur together more or less often than expected by chance
Locus Heterogeneity
Mutations at different loci produce the same/similar phenotype
Allelic Heterogeneity
Different mutations in the same locus produce the same phenotype
Heteroplasmy
presence of both normal and mutated mitochondrial DNA
Heterozygous Uniparental Disomy
Occurs with meiosis I error
Homozygous Uniparental Disomy
Occurs with meiosis II error
Prader-Willi Syndrome
Silent maternal gene, deleted/mutated paternal
25% are maternal uniparental disomy
Angelman syndrome
Silent paternal gene, deleted/mutated maternal gene
only 5% are paternal uniparental disomy
Autosomal Dominant Polycystic Kidney Disease
85% are PKD1 mutation (chr 16) remainder are PKD2 (chr 4)
Bilateral enlarged kidneys, cysts
Familial Adenomatous Polyposis
chromosome 5q (APC) mutation Colon covered in polyps, resect or develop cancer
Familial Hypercholesterolemia
Defective or absent LDL Receptor
Hereditary Hemorrhagic Telangectasia
Branching skin lesions, recurrent epistaxis, skin discoloration, GI bleeding, hematuria
Hereditary Spherocytosis
spectrin or ankryn defects cause hemolytic anemia
Huntington Disease
CAG trinucleotide repeat on chromosome 4
Exhibits anticipation
Li-Fraumeni Syndrome
TP53 abnormality, many cancers at early age
Marfan Syndrome
FBN1 mutation on chromosome 15 (fibrin)
Sympt: tall, long extremities, pectus excavatum, medial necrosis of aorta, floppy mitral valve
Multiple endocrine neoplasias
Familial tumors of endocrine glands
Neurofibromatosis type I
Café au lait spots, cutaneous neurofibromas, optic gliomas, pheochromocytomas, Lisch nodules
AD, 100% penetrant with variable expression
Mutation in NF1 gene on chr 17
Neurofibromatosis type II
bilateral acoustic schwannomas, juvenile cataracts, meningiomas
Mutation in NF2 on chromosome 22
Tuberous Sclerosis
numerous benign hamartomas
Incomplete penetrance, variable expression
von Hippel Lindau
Numerous tumors, associated with VHL deletion on chromosome 3
Cystic Fibrosis
Most common caucasian genetic disease, CFTR defect on chromosome 7.
Most common mutation is folding problem that traps in RER, less chloride out keeps water in and draws sodium in. Thick secretions.
High chloride in sweat.
Duchenne MD
Frameshift truncating dystrophin protein, longest protein in human body on X chromosome.
Onset before 5 years, Gower maneuver, pseudohypertrophy of calf
Dystrophin
Connects cytoskeleton to alpha and beta dystroglycan transmembrane proteins which connect to the ECM
Becker MD
Non-frameshift, insertions into dystrophin so it is partially functional
Myotonic Dystrophy Type I
AD, CTG trinucleotide repeat expansion of DMPK gene
Symptoms: My Tonia, My Testicles (atrophy), My Toupee (Frontal balding), My Ticker (Arrhythmia)
Fragile X
CGG trinucleotide repeat of FMR1 gene
Symptoms: enlarged testicles, large jaw, large ears, autism, mitral prolapse
Trinucleotide Repeat Diseases
Fragile X Syndrome, X, FMR1, CGG
Friedreich Ataxia, GAA
Huntington Chr 4, Huntington, CAG
Myotonic Dystrophy, DMPK, CTG
Try Hunting for My Fried Eggs
X-Girlfriend’s First Aid Helped Ace My Test
Down Syndrome
Trisomy 21, 1:700
Symptoms: retardation, flat facies, single palmar crease, early onset Alzheimer’s, high risk of AML/ALL, etc.
Associated w/ maternal nondisjunction in 95% of cases, 4% Robertsonian translocation, 1% mosaicism
1st Trimester: serum PAPP-A is low, free beta-HCG is high
2nd Trimester: low alpha-fetoprotein, high beta-HCG, low estriol, high inhibin A
Edwards Syndrome
Trisomy 18; 1:8000
Symptoms: retardation, rocker-bottom feet, micrognathia, low set ears, clenched hands
First trimester: low PAPP-A & beta-HCG
Second Trimester: low alpha fetoprotein, beta-HCG, estriol, inhibin A
Patau Syndrome
Trisomy 13; 1:15000
Symptoms: retardation, rocker-bottom feet, microphthalmia, microcephaly, cleft lip/palate, holoprosencephaly, polydactyly
First Trimester: low beta-HCG, PAPP-A and increased nuchal translucency
Cri-du-chat Syndrome
microdeletion of short arm of chromosome 5
Symptoms: microcephaly, retardation, high pitched crying, epicanthal folds
Williams Syndrome
Microdeletion of long arm of chromosome 7 (elastin)
Symptoms: “elfin” facies, retardation, hypercalcemia, extreme friendliness
22q11 Deletion Syndromes
Adherent development of 3 and 4 branchial pouches
Symptoms are CATCH-22
Cleft palate Abnormal facies Thymic aplasia (t cell deficient) Cardiac defects Hypocalcemia
Two 22q11 deletion syndromes
DiGeorge Syndrome (thymus, thyroid, and cardiac defects) Velocardiofacial syndrome (palate, facial, and cardiac defects)
