Genetics

Question 1

Codominance

Answer 1

Both alleles contribute to phenotype — blood groups AB

Question 2

Variable expressivity

Answer 2

Phenotype varies among individuals with same genotype

Question 3

Incomplete penetrance

Answer 3

Not all individuals with mutant genotype have mutant phenotype

Question 4

Pleiotropy

Answer 4

One gene contributes to multiple phenotypic situations

Question 5

Anticipation

Answer 5

Increased severity or earlier onset of disease – trinucleotide repeat disorders (Huntington, Fragile X, Myotonic dystrophy, Freiderich Ataxia)

Question 6

Loss of heterozygosity

Answer 6

Tumor suppressor genes – must lose the second abnormal allele to have cancer

Question 7

Dominant negative mutation

Answer 7

Heterozygote produces a nonfunctional altered protein that also prevents the normal gene product from functioning

Question 8

Linkage disequilibrium

Answer 8

Certain alleles at 2 linked loci to occur together more or less often than expected (can occur even if on 2 different chromosomes)

Question 9

Mosaicism

Answer 9

Genetically distinct cell lines in same individual

Question 10

McCune-Albright syndrome

Answer 10

Mutation affecting G-protein signaling — unilateral cafe au lati spots, polyostotic fibrous dysplasia, precocious puberty, multiple endocrine abnormalities

Question 11

Locus heterogeneity

Answer 11

Mutations at different loci can produce a similar phenotype - Albinism

Question 12

Allelic heterogeneity

Answer 12

Different mutations at same locus produce the same phenotype - B-thalassemia

Question 13

Heteroplasmy

Answer 13

Presence of both normal and mutated mtDNA (variable expression in MITOCHONDRIA inherited disease)

Question 14

Uniparental disomy

Answer 14

2 copies of a chromosome from 1 parent and no copies from the other parent — heterodisomy (meiosis I error) or isodisomy (meiosis II error)

Question 15

Hardy Weinberg assumptions

Answer 15

No mutation occurring at locus, natural selection not occurring, completely random mating, no net migration — p2 + 2pq + q1 = 1 and p+q = 1

Question 16

Prader Willi syndrome

Answer 16

Maternal imprinting (DNA methylation) — gene from mom is normally silent and Paternal gene is deleted (chromosome 15) — hyperphagia, obesity, intellectual disability, hypogonadism, hypotonia

Question 17

AngelMan syndrome

Answer 17

Only (Man) — Paternal imprinting (DNA methylation) – gene from dad is normally silent and maternal gene is deleted/mutated (chromosome 15) — inappropriate laughter, seizures, ataxia, severe intellectual disability

Question 18

Autosomal dominant

Answer 18

Structural gene defects – often pleiotropic and variably expressive

Question 19

Autosomal recessive

Answer 19

Often due to enzyme deficiencies — increased risk in consanguineous families

Question 20

X-linked recessive

Answer 20

Sons of carrier mom have a 50% chance of being affected, no male to male transmission, daughters of affected males are carriers

Question 21

X-linked dominant

Answer 21

Mothers transmit to 50% of daughters and sons, fathers transmit to all daughter but no sons — Ex: hypophosphatemic rickets (increased phosphate wasting at proximal tubule)

Question 22

Mitochondrial inheritance

Answer 22

Transmitted only through mom – all offspring of affected females have signs of disease – ragged red fibers on muscle biopsy

Question 23

Autosomal Dominant disease list

Answer 23

Very Powerful DOMINANT Humans — Von willebrand/Von hippel-lindau – Pseudo-hypoparathyroidism – Dystrophia myotonica – Osteogenesis imperfeca/Osler-weber-rendu – Marfan syndrome – Intermittent porphyria – Neurofibromatosis – Achondroplasia/Adult polycystic kidney disease – Noonan syndrome – Tuberous sclerosis – Hypercholesterolemia – Huntington’s disease – Hypertrophic obstructive cardiomyopathy – Hereditary spherocytosis – HNPCC – Hereditary hemorrhagic telangiectasia —- others on list not in mnemonic: Familial adenomatous polyposis, Li-Fraumeni, MEN

Question 24

Hereditary hemorrhagic telangiectasia

Answer 24

Disorder of blood vessels – branching skin lesions (telangiectasia), recurrent epistaxis, skin discolorations, arteriovenous malformations, GI bleeding, hematuria (Osler-Weber-Rendu)

Question 25

Li Fraumeni syndrome

Answer 25

Abnormalities in TP53 - multiple malignancies at an early age — SBLA cancer syndrome (Sarcoma, Breast, Leukemia, Adrenal gland)

Question 26

Marfan syndrome

Answer 26

FBN1 gene mutation on chromosome 15 – defective FIBRILLIN (elastin) – tall with long extremities, pectus excavatum, hypermobile joints, long fingers and toes, cystic medial necrosis of aorta (aortic aneurysms/dissection), mitral valve prolapse, subluxation of lens (upward and temporally)

Question 27

Cystic fibrosis genetics/path

Answer 27

Autosomal recessive, defect in CFTR (normally secretes Cl- in lungs and GI tract and reabsorbs Cl- in sweat glands) gene on chromosome 7 (Phe508 deletion) — Misfolded protein causes decreased Cl and H2O secretion –> intracellular Cl results in compensatory Na reabsorption and H2O reabsorption –> abnormally thick mucus in lungs and GI tract (pancreas) —- Diagnose with Chloride sweat test, contraction alkalosis, hypokalemia, increased immunoreactive trypsinogen

Question 28

CF complications/treatment

Answer 28

Recurrent pulmonary infections (Pseudomonas), chronic bronchitis and bronchiectasis, pancreatic insufficiency, malabsorption and steatorrhea, nasal polyps, meconium ileus in newborns, infertility in males (absence of vas deferens), subfertility in females, fat soluble vitamin deficiencies — Tx: N-acetylcysteine to loosen mucus plugs (cleaves disuflide bonds)

Question 29

X-linked recessive disorders list

Answer 29

Be Wise, Fool’s GOLD Heeds Silly HOpe —- Bruton agammaglobulinemia, Wiskott-Aldrich syndrome, Fabry disease, G6PD deficiency, Ocular albinism, Lesch-Nyhan syndrome, Duchenne mucular dystrophy, Hunter Syndrome, Hemophilia A and B, ornithine transcarbamylase deficiency

Question 30

Duchenne muscular dystrophy

Answer 30

X-linked disorder from frameshift mutation –> truncated dystrophin protein –> inhibited muscle regeneration —- weakness begins in pelvic girdle and progresses up, pseudohypertrophy of calf muscles (fibrofatty replacement), Gower maneuver —- BEFORE AGE 5! – Dilated cardiomyopathy —- DMD gene mutation (lack of dystrophin - normally connects intracellular cytoskeleton to transmembrane proteins a and B-dystroglycan)

Question 31

Becker muscular dystrophy

Answer 31

X-linked disorder with non-frameshift mutation –> partially functional truncated dystrophin protein –> TEENAGE/EARLY ADULT

Question 32

Myotonic type 1

Answer 32

Autosomal dominant - CTG trinucleotide repeat expansion in DMPK gene – abnormal myotin protein kinase –> myotonia, muscle wasting, cataracts, testicular atrophy, frontal balding, arrhythmia

Question 33

Fragile X syndrome

Answer 33

Affects methylation and expression of FMR1 gene — intellectual disability, post-pubertal macroorchidism, long face with large jaw, large everted ears, autism, mitral valve prolapse

Question 34

Down syndrome

Answer 34

Trisomy 21 - intellectual disability, flat facies, epicanthal folds, single palmar crease, duodenal atresia, Hirschsprung disease, atrial septal defect, early onset Alzheimer, increased risk ALL — most due to meotic nondisjunction (maternal meosis I – advanced maternal age), others due to Robertsonian translocation — Quad screen shows decreased AFP, increased BhCG, decreased estriol, increased inhibin A

Question 35

Edwards syndrome

Answer 35

Trisomy 18 - small jaw, low set ears, clenched hands, overlapping fingers, Meckel’s diverticulum, death within 1 year — quad screen shows low everything

Question 36

Patau syndrome

Answer 36

Trisomy 13 - cleft lip/palate, hosoprosencephaly, polydactyly, PDA/ASD/VSD, polycystic kidneys, gastric wall defects death within 1 week

Question 37

Robertsonian translocation

Answer 37

Involves chromosomes 13, 14, 15, 21, and 22 — long arms of 2 acrocentric chromosomes fuse at centromere and 2 short arms are lost

Question 38

Cri-du-chat syndrome

Answer 38

Microdeletion of short arm of chromosome 5 — microcephaly, high pitched crying, epicanthal folds, VSD

Question 39

Williams syndrome

Answer 39

Microdeletion of chromosome 7 long arm — elfin facies, hypercalcemia, extreme friendliness with strangers, CV problems

Question 40

22q11 deletion

Answer 40

CATCH22 - Cleft palate, Abnormal facies, Thymic aplasia, Cardiac defects (conotruncal - truncus arteriosus, tetralogy), Hypocalcemia — DiGeorge and Velocardiofacial syndromes