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Flashcards in genetics Deck (91):
1

variable expression

nature and severity of phenotype vary from one person to another

2

incomplete penetrance

not all individuals with a mutant genotype show the mutant phenotype

3

pleiotropy

one gene has more than one effect on phenotype (i.e. MULTIPLE phenotypes, seemingly unrelated)

4

imprinting

differences in phenotype depend on whether mutation is of maternal or paternal origin

5

anticipation

severity of disease worsens OR
age of onset of disease is early
in succeeding generations

6

loss of heterozygosity

if a pt inherits or develops a mutation in a tumor suppressor gene, the complementary allele must be deleted or mutated before cancer develops (TWO-HIT HYPOTHESIS).

*not true of oncogenes

7

dominant negative mutation

exerts dominant effect.
heterozygote produces nonfunctional altered protein that also prevents normal gene product from functioning.

8

linkage disequilibrium

tendency for certain alleles at 2 linked loci to occur together more often than expected by chance.

measure in POPULATION, not family.
often varies in diff pops.

9

mosaicism

occurs when cells in body differ in genetic makeup due to postfertilization loss of genetic info during mitosis

10

germline (gonadal) mosaicism

produce disease that is not carried by parents' somatic cells

11

locus heterogeneity

mutations at diff loci can produce same phenotype

ex: Marfan, MEN 2B, and homocystinuria (all produce marfanoid habitus)

12

heteroplasmy

presence of both normal and mutated mtDNA, resulting in variable expression of mitochondrial inherited dz

13

uniparental disomy

offspring receives 2 copies of chromosomes from 1 parent and no copies from other parent

14

Hardy-Weinberg law assumes...

1. no mutation occurring at locus.
2. no selection for any of the genotypes at the locus.
3. completely random mating.
4. no migration.

15

cause of imprinting

at some loci, only ONE allele is active - the other is inactive (imprinted/inactivated by methylation).

with one allele inactivated, deletion of the ACTIVE ALLELE = disease.

16

Prader-Willi syndrome

imprinting.
chromo 15.

maternal allele inactivated.
Paternal allele should be active but is not expressed.

17

features of Prader-Willi

mental retardation.
hyperphagia.
obesity.
hypogonadism.
hypotonia.
short stature.
thirst.
emotional lability.

18

AngelMan's syndrome

imprinting.
chromo 15.

paternal allele inactivated.
Maternal allele should be active but is not expressed.

19

features of Angelman's syndrome

mental retardation.
seizures.
ataxia.
inappropriate laughter.
HAPPY PUPPET.

20

which mode of inheritance is often due to defects in structural genes?

AD

21

which mode of inheritance is often pleiotropic?

AD

22

which mode of inheritance often presents clinically after puberty?

AD

23

for which mode of inheritance is fam hx crucial for dx?

AD

24

which mode of inheritance is often due to enzyme deficiencies?

AR

25

how does AR compare to AD clinically?

AR more severe,
present in childhood.

26

which mode of inheritance is usually seen in only one generation?

AR

27

which mode of inheritance has NO MALE-to-MALE transmission?

X-linked R

28

which mode of inheritance guarantees disease in female offspring of affected father?

X-linked D

29

hypophosphatemic rickets

X-linked D disorder with increased phosphate wasting at prox tubule. presents like rickets.

30

which mode of inheritance is ONLY transmitted through MOTHER?

mitochondrial
(all offspring may show signs of disease)

31

which mode of inheritance is often due to failures in oxidative phosphorylation?

mitochondrial

32

why do mitochondrial disease have variable expression?

heteroplasmy

33

mitochondrial myopathies

ragged red fibers on microscopy due to abn mito accumulation under sarcolemma.

1. Leber's hereditary optic neuropathy.
2. myoclonic epilepsy.
3. mitochondrial encephalopathy.

34

mitochondrial myopathy: Leber's hereditary optic neuropathy

acute loss of central vision

35

mitochondrial myopathy: mitochondrial encephalopathy

stroke-like episodes.
lactic acidosis.

36

AR disorders

albinism.
ARPKD.
CF.
glycogen storage.
hemochromatosis.
mucopolysaccharidoses (except Hunter's).
PKU.
sickle cell.
sphingolipidoses (except Fabry's).
thalassemias.

37

cystic fibrosis

AR defect in CFTR gene.
chromo 7.
deletion of Phe508.

38

CFTR channel

actively secretes Cl in lungs and GI tract.
actively reabsorbes Cl from sweat.

activated by cAMP-mediated phosphorylation.

gated by ATP.

39

what does the CFTR mutation do?

cause abnormal protein folding (defective glycosylation), resulting in DEGRADATION of channel before it reaches cell surf.

40

clinical features of CF

defective Cl channel = secretion of abnormally thick mucus that plugs lungs, pancreas, liver.

recurrent pulmo infx.
chronic bronchitis.
bronchiectasis.
pancreatic insuff.
nasal polyps.
meconium ileus in newborn.

41

what microorganisms tend to cause pulmo infx in CF?

Pseudomonas.
S.aureus.

42

what is the result of pancreatic insuff in CF?

malabsorption.
fat-soluble vit deficiency.
steatorrhea.

failure to thrive in infancy.

43

how does CF cause infertility in males?

BILATERAL absence of vas deferens

44

DX of CF

increased Cl ions in sweat test

45

TX of CF

N-acetylcysteine:
loosens mucous plugs by cleaving disulfide bonds w/in mucous glycoproteins.

46

X-linked recessive disorders

"Be Wise, Fool's GOLD Heeds Silly Hope"

Bruton's agammaglobulinemia.
Wiskott-aldrich.
Fabry's dz.
G6PD def.
Ocular albinism/OTC def.
Lesch-nyhan.
Duchenne/becker MD.
Hunter's Syndrome.
Hemophilia a and b.

47

why are female carriers rarely affected by X-linked recessive disorder?

random inactivation of X chromo in each cell

48

Duchenne muscular dystrophy (DMD)

X-linked FRAME SHIFT mutation leading to DELETION of DYSTROPHIN GENE.

accelerated muscle breakdown.

49

where does muscle weakness begin in DMD?

pelvic girdle mm.
progress superiorly.

50

features of DMD

muscle weakness.
walking difficulties (waddle).
calf PSEUDOHYPERTROPHY.
cardiac myopathy.
kyphoscoliosis.

onset before age 5.

51

calf pseudohypertrophy in DMD

fibrofatty replacement of muscle

52

what is the consequence of DMD gene being the longest known human gene?

increased rate of spontaneous mutation

53

normal function of dystrophin

help anchor muscle fibers, primarily in skeletal and cardiac muscle

54

Gower's maneuver in DMD

child uses upper extremities to help in standing up from the ground

55

DX of DMD

increase CPK (creatine phosphokinase).

muscle biopsy: varied fiber size and shape. increased conn tissue.

56

Becker's muscular dystrophy

X-linked mutated dystrophin gene.
less severe than DMD.
onset in adolescence or early adulthood.

57

fragile X syndrome

X-linked defect affecting methylation and expression of FMR1 gene.

TRINUCLEOTIDE REPEAT disorder (CGG).

58

findings in fragile X syndrome

macro-orchidism.
long face, large jaw.
large everted ears.
autism.
mitral valve prolapse.

X-tra large testes, jaw, ears

59

what is the 2nd most common cause of genetic MR?

fragile X.
#1 is Down.

60

trinucleotide repeat expansion disorders

Huntington's.
Myotonic dystrophy.
Friedrich's ataxia.
Fragile X syndrome.

61

trinucleotide repeat in Huntington's

CAG

62

trinucleotide repeat in Myotonic dystrophy

CTG

63

trinucleotide repeat in Friedrich's ataxia

GAA

64

trinucleotide repeat in Fragile X

CGG

65

increased #trinucleotide repeats means...?

earlier onset of disease, increased severity (GENETIC ANTICIPATION)

66

when does EXPANSION of trinucleotide repeats occur?

during parental transmission

67

Down syndrome

trisomy 21.
most common chromo d/o.
most common cause of genetic MR.

68

95% Down syndrome cases due to?

meiotic nondisjunction of homologous chromosomes- assoc with advanced maternal age

69

4% Down syndrome cases due to ?

robertsonian translocation: break near centromeres, transfer of genetic material between chromos.

t(14;21) or t(21;22)

70

1% Down syndrome cases due to?

Down mosaicism (no maternal assoc)

71

findings in Down syndrome

MR.
flat facies.
prominent epicanthal folds.
simian crease.
gap between 1st 2 toes.
cleft palate.
hypotonia.
*organ involvement*

72

congenital heart defects in Down syndrome

most common: osmium primum-type ASD.
endocardial cushion defects.

73

hematologic malignancy in Down syndrome

increased risk of ALL.
also AML (M7).

74

GI defect in Down syndrome

duodenal atresia

75

neuro defect in Down syndrome

early-onset Alzheimer disease after age 35

76

preg quad screen in Down syndrome

decrease AFP.
increase b-HCG.
decrease estriol.
increase inhibin A.

77

ultrasound in Down syndrome

increase nuchal translucency

78

Edwards syndrome

trisomy 18.
most common trisomy resulting in LIVE birth, following Down.

79

findings in Edwards syndrome

severe MR.
rocker bottom feet.
micrognathia (jaw).
low-set ears.
clenched hands**
prominent occiput.
cong heart dz.

death usually w/in 1 year.

80

preg quad screen in Edwards syndrome

decrease AFP.
decrease b-HCG.
decrease estriol.
normal inhibin A.

81

Patau syndrome

trisomy 13.
severe MR.
rocker bottom feet.
microphthalmia.
microcephaly.
HOLOPROSENCEPHALY.
cleft lip/palate.
polydactyly.
cong heart dz.

death usually w/in 1 year.

82

preg quad screen in Patau syndrome

normal AFP.
normal b-HCG.
normal estriol.
normal inhibin A.

83

robertsonian translocation

nonreciprocal translocation when long arms of 2 acrocentric (centromeres near end) chromos fuse at the centromere and the short arms are lost

84

chromos usually involved in robertsonian translocation are...?

pairs 13, 14, 15, 21, 22

85

balanced robertsonian translocation

normally do not cause any abn phenotype

86

unbalanced robertsonian translocation

miscarriage.
still birth.
chromo imbalance (trisomies).

87

Cri-du-chat syndrome

congenital microdeletion of short arm of chromo 5 (5p-).

microcephaly.
moderate to severe MR.
HIGH-PITCHED crying/mewing.
epicanthal folds.
cardiac abn (VSD).

88

Williams syndrome

congenital microdeletion of long arm chromo 7 (includes ELASTIN gene).

distinct "elfin" facies.
MR.
hypercalcemia (sensitive to vit D).
well-developed verbal skills.
extreme FRIENDLINESS with strangers.
cardio problems.

89

22q11 deletion syndromes

variable presentation: CATCH-22.
Cleft palate.
Abn facies.
Thymic aplasia (T cell def).
Cardiac defects.
Hypocalcemia second to parathyroid aplasia.

*due to aberrant development of 3rd and 4th branchial/pharyngeal POUCHES.

*includes DiGeorge and velocardiofacial syndromes

90

DiGeorge syndrome

CATCH-22 with
thymic, parathyroid, cardiac defects

91

velocardiofacial syndrome

CATCH-22 with
palate, facial, cardiac defects