Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
45 Cards in this Set
- Front
- Back
|
Codominance |
Both alleles contribute to phenotype of heteroZ Blood groups A/B/AB, A1AT |
|
|
Variable expressivity |
Phenotype varies among individuals with same genotype |
|
|
Incomplete penetrance |
Not all individuals with a mutant genotype show the mutant phenotype BRAC1 doesn't always = breast/ovarian cancer |
|
|
Pleiotropy |
One gene contributes to multiple phenotypic effects |
|
|
Anticipation |
Increased severity/earlier onset of disease in succeeding generations TriN repeat dxs - Huntington |
|
|
Loss of heterozygosity |
If pt inherits/develops a mutation in TSG, the complementary allele must be deleted/mutated before cancer develops Not true of oncogenes Retinoblastoma |
|
|
Dominant negative mutation |
Exerts a dominant effect HeteroZ produces a nonfxnional altered protein - also prevents the normal gene product from fxning |
|
|
Linkage disequillibrium |
Tendency for certain alleles at 2 linked loci to occur together more or less often than expected by chance Measured in population not family |
|
|
Mosaicism |
Presence of genetically distinct cell lines in same individual Somatic M = mutation arises from mitotic errors after fertilisation and propogates through multiple tissues/organs Gonadal M = mutation only in egg/sperm cells |
|
|
McCune-Albright syndrome |
Due to mutation affecting G-protein signalling PC: Unilateral cafe-au-lait spots, polyostotic fibrous dysplasia, precocious puberty, multiple endocrine ABs Lethal if occurs before fertilisation Survivable in pts with mosaicism |
|
|
Locus heterogenity |
Mutations at different loci can produce a similar phenotype Albinism |
|
|
Allelic heterogenity |
Different mutations in same locus produce same phenotype Beta-thalassemia |
|
|
Heteroplasmy |
Presence of both normal and mutated mtDNA => variable expression in mitochondrially inherited disease |
|
|
Uniparental disomy |
Offspring receives 2 copies of a chromosome from 1 parent and no copies from other Heterodisomy = heteroZ = meiosis 1 error Isodisomy = homoZ = meiosis 2 error/postzygotic chromosomal duplication of one/pair of chromosomes + loss of original pair |
|
|
Imprinting |
Only one allele active at some loci Other inactive - imprinted/inactivated by methylation One allele inactivated - deletion of other = disease |
|
|
Prader-Willi syndrome |
Maternal imprinting Gene from M silent, Gene from P deleted/mutated Hyperphagia, obesity, intellectual disability, hypogonadism, hypotonia 25% of cases due to maternally uniparental disomy = 2 maternal imprinted genes received, no paternal |
|
|
Angelman syndrome |
Paternal imprinting Gene from P silent, gene from M deleted/mutated Inappropriate laughter, seizures, ataxia, severe intellectual disability 5% due to paternal uniparental disomy |
|
|
AD diseases |
APCKD, FAP, familial hypercholesterolemia, HHT, hereditary spherocytosis, Huntington disease, Li-Fraumeni syndrome, Marfan syndrome, MEN, Neurofibromatosis (types 1 + 2), tuberous sclerosis, von Hippel-Lindau disease |
|
|
AR diseases |
Albinism, ARPCKD, CF, Glyogen storage diseases, haemochromotosis, Kartagener syndrome, mucopolysaccharidoses (-Hunter syndrome), phenylketonuria, sickle cell anaemia, sphingolipidoses (-Fabry dx), thalassemias, Wilson disease |
|
|
X-linked recessive disorders |
Bruton agammaglobulinemia, Wiskott-Aldrich syndrome, Fabry disease, G6PD deficiency, Ocular albinism, Lesch-Nyhan syndrome, Duchenne + Becker muscular dystrophy, Hunter syndrome, Haemophilia A/B, Ornithine transcarbamylase deficiency Be Wise Fool's GOLD Heeds Silly HOpe Female carriers can be variably affected - depends on % of inactivation of mutant X |
|
|
Trinucleotide repeat expansion diseases |
Fragile X syndrome = CGG Friedreich ataxia = GAA Huntington disease = CAG Myotonic dystrophy = CTG May show genetic anticipation - disease severity increases and age of onset decreases in successive generations |
|
|
Down Syndrome |
T21 Intellectual disability, flat facies, prominent epicanthal folds, single palmar crease, gap twixt 1st 2 toes, duodenal atresia, Hirschsprung disease, ASD, Brushfield spots A/W early-onset Alzheimer dx - 21 codes for APP Increased risk of ALL/AML 95% due to meiotic nondisjxn - A/W advanced maternal age 4% due to Robertsonian translocation 1% due to mosaicism 1st semester US = increased nuchal translucency, hypoplastic nasal bone, serum PAPPA-A decreased, free beta-HCG increased 2nd trimester quad screen = decreased AFP, increased beta-HCG, decreased estriol, increased inhibin A |
|
|
Edwards syndrome |
T18 Severe intellectual disability, rocker-bottom feet, micrognathia, low-set ears, clenched hands with overlapping fingers, prominent occiput, CHD Death usually within year of birth 1st trimester = PAPP-A + beta-HCG decreased Decreased AFP/beta-HCG/estriol/inhibin A |
|
|
Patau syndrome |
T13 Severe intellectual disability, rocker-bottom feet, microphthalmia, microcephaly, cleft lip/palate, holoprosencephaly, polydactyly, CHD, cutis aplasia Death occurs within 1 year of birth 1st trimester = decreased free beta-HCG/PAPPA-A, increased nuchal translucency |
|
|
Chromosome 3 |
Von Hippel-Lindau dx Renal cell carcinoma |
|
|
Chromosome 4 |
ADPCKD + PKD2 defect Huntington disease |
|
|
Chromosome 5 |
Cri-du-chat syndrome FAP |
|
|
Chromosome 7 |
Williams syndrome CF |
|
|
Chromosome 9 |
Friedreich ataxia |
|
|
Chromosome 11 |
Wilms tumour |
|
|
Chromosome 13 |
Patau syndrome, Wilson disease |
|
|
Chromosome 15 |
Prader-Willi syndrome Angelman syndrome |
|
|
Chromosome 16 |
ADPCKD + PKD1 defect |
|
|
Chromosome 17 |
Neurofibromatosis type 1 |
|
|
Chromosome 18 |
Edwards syndrome |
|
|
Chromosome 21 |
Down syndrome |
|
|
Chromosome 22 |
Neurofibromatosis type 2 DiGeorge syndrome (22q11) |
|
|
Robertsonian translocation |
Involves pairs 13/14/15/21/22 Long arms of 2 acrocentric chromosomes (have centromeres near their ends) fuse at centromere = 2 short arms lost Balanced - don't cause any AB phenotype Unbalanced - can result in miscarriage, stillbirth, chromosomal imbalance |
|
|
Cri-du-chat syndrome |
Congential microdeletion of short arm of chromosome 5 = 46XX/Y 5p- Microcephaly, moderate to severe intellectual disability, high-pitched crying/mewing, epicanthal folds, VSD |
|
|
Williams syndrome |
Congenital microdeletion of long arm of chromosome 7 Deleted region includes elastin gene Elfin facies, intellectual disability, hypercalcaemia (increased sensitivity to vitamin D), well-developed verbal skills, extreme friendliness with strangers, cardiovascular problems |
|
|
22q11 deletion syndromes |
Microdeletion at chromosome 22q11 = variable PCs Cleft palate, AB facies, Thymic aplasia (-> T cell def), Cardiac defects, Hypocalcemia secondary to parathyroid aplasia CATCH-22 Due to aberrant development of 3rd/4th branchial pouches DiGeorge syndrome = thymic, parathyroid, cardiac defects Velocardiofacial syndrome = palate, facial, cardiac defects |
|
|
Fragile X syndrome |
X-linked defect - affects methylation and expression of FMR1 gene Post-pubertal macroorchidism (enlarged testes), long face with large jaw, large inverted ears, autism, mitral valve prolapse CGG |
|
|
Duchenne muscular dystrophy |
X-linked - due to frameshift mutations Truncated dystrophin protein -> inhibited muscle regeneration Weakness begins in pelvic girdle muscles, progresses superiorly Pseudohypertrophy of calf muscles due to fibrofatty replacement of muscle Gower maneuver - pts use upper limbs to help them stand up Waddling gait Onset before 5yo Death - dilated cardiomyopathy DELETED DYSTROPHIN - dystrophin gene (DMD) helps anchor muscle fibres in skeletal and cardiac muscle, connects actin to transmembrane proteins alpha- and beta-dystroglycan Loss of dystrophin -> myonecrosis Increased CPK and aldolase Western blot and muscle bx confirm dx |
|
|
Becker muscular dystrophy |
X-linked - due to non-frameshift insertions in dystrophin gene Less severe than Duchenne Onset in adolescence/early adulthood |
|
|
Myotonic muscular dystrophy type 1 |
AD CTG triN repeat expansion in DMPK gene -> AB expression of myotonin protein kinase -> myotonia, muscle wasting, cataracts, testicular atrophy, frontal balding, arrhythmia MyTonia, My Testicles, My Toupee, My Ticker |
