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Flashcards in Genetics Deck (85):
1

Pleiotropy

more than one phenotype for a given genetic mutation (ie PKU)

2

Imprinting

Difference in phenotype depend on whether mutation is maternal or paternal origin; Prader Willi and Angelman's syndromes

3

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)

4

Linkage disequilibrium

When two alleles occur together more often than would be expected by chance alone.

5

Mosaicism

Loss of genetic information during mitosis; Lyonization, Mutation in the embryonic precursor of the bone marrow stem cell

6

Locus heterogeneity

One phenotype from produced by different loci mutations; Marfan's syndrome, MEN 2B, albinism, homocystinuria

7

Heteroplasmy

Presence of normal and mutated mtDNA results in variable expression of mito inherited disease

8

Uniparental disome

Offspring receive 2 copies from one parent and none from the other.

9

Prader-Willi syndrome

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

10

Angelman's syndrome

Normally inactivated paternal allele is active. Maternal allele is either deleted, inactivated, or uniparental disomy of father; Mental retardation, seizures, ataxia, inappropriate laughter

11

Patau syndrome

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

12

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.

13

Hemophilia B/A Disorder's Inheritance is

X-linked recessive

14

Huntington inheritance

autosomal dominant

15

Lesch-Nyhan inheritance

X-linked recessive

16

Leber hereditary optic neuropathy inheritance

mitochondrial

17

t(8;14)

Burkitt's lymphoma; myc protooncogene is moved to 14 in front of immunoglobulin heavy chain.

18

t(9;22)

CML; bre-abl

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t(11;14)

Mantle cell lymphoma; Activation of cyclin D gene

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13q deletion

CLL association

21

t(15;17)

AML M3

22

3p deletion

Von Hippel-Lindau; autosomal dominant; medullary, cerebellar, and retinal hemangioblastomas; pheochromocytomas; pancreatic, hepatic, renal cysts; renal cell carcinoma

23

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

24

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

25

Cystic hygromas

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

26

Congenital Hypothyroidism

lethargic, poor feeding, prolonged jaundice, constipation, hypotonia, pale cool skin, myxedema; Umbilical Hernia, increased risk of heart defects. T4 is essential for myelination

27

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.

28

Pick bodies

eosinophilic intracytoplasmic inclusions in cortical neurons in Pick disease

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Lewy Bodies

inclusions that contain neurofilaments seen in neurons of substantia nigra in Parkinson

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Conditions associated with Downs

AML, ALL, Parkinson, Hirschsprungs and Duodenal atresia

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Neurofibrillary tangles

beta-amyloid accumulation in brain tissue and vessel walls.

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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.

33

Reassortment

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

34

Recombination

exchange of genes between two chromosomes (dsDNA) by crossing over within homologous regions.

35

Transformation

uptake of naked DNA by prokaryotic or eukaryotic cell.

36

Interference

inhibition by one virus of the replication and or release of a second virus that is infecting the same cell.

37

G6PD deficiency inheritance

X-linked Recessive

38

t(14;18)

Follicular lymphoma, Bcl-2

39

ErbB2, HER2, neu

same name for epidermal growth factor receptor which is overexpressed in many booby cancers

40

Sturge-Weber Syndrome

vascular disorder characterized by facial port-wine stain and leptomeningeal angioma

41

NF1

chr. 17, autosomal dominant. Café au lait, neurofibromas, optic nerve gliomas, Lisch nodules, bony abnormalities; meningiomas, gliomas, pheochromocytomas.

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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)

43

Early-onset alzheimer disease

associated with APP (Chr 21) and Presenilin 1 and 2

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Late-Onset alzheimer disease

Associated with apolipoprotein E4

45

Kartagener inheritance

Autosomal recessive microtubular defect

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Tuberous Sclerosis inheritance

autosomal dominant

47

Friedrich's ataxia inheritance

autosomal recessive

48

Marfan syndrome

autosomal dominant

49

Kallmann syndrome

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.

50

Xeroderma pigmentosa iheritance

DNA excision repair defect that is Autosomal Recessive

51

Bloom syndrome

Autosomal recessive

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Fanconi anemia

autosomal recessive

53

Klinefelter syndrome is inherited through

an extra sex chormosome acquired due to meiotic nondisjunction during gametogenesis. XXY

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Androgenic alopecia

polygenic inheritance with variable penetrance.

55

Common conditions with polygenic inheritance

Androgenetic alopecia, epilepsy, ischemic heart disease, schizophrenia, glaucoma, HTN, malignancy, Type 2 DM

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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

57

ADPKD

AD, PKD1 [integral membrane protein, signal transducer; renal tubular development] mutation on Chr 16; berry aneurysms, mitrial valve prolapse

58

FAP

Familial adenomatous polyposis; Chromosome 5, APC gene (mismatch repair) Autosomal dominant

59

Familial hypercholesterolemia (IIA)

AD; defective or absent LDL receptor; high LDL; major atherosclerosis, xanthomas etc.

60

Osler-Weber-Rendu (Hereditary hemorrhagic telangiectasia)

AD; Blood vessel disorder with telangiectasia epistaxis, skin discoloration and AVMs

61

Hereditary Spherocytosis

AD; spectrin or ankyrin defect; increased MCHC

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Huntington disease

AD; Chromosome 4; CAG

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Marfan

AD

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MEN syndrome

AD; 2A and 2B associated with Ret gene

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NF2

chromosome 22; AD; mutation in merlin; bilateral acoustic schwannomas; juvenile cataract

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von Hippel Lindeau

AD; deletion of VHL on Chr 3; constitutive expression of HIF that activates angiogenic growth factors

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cystic fibrosis

AR

68

Glycogen storage diseases

AR

69

Hemochromatosis

AR

70

Mucopolysaccharidosis

AR (except Hunter's - X-linked)

71

PKU

AR

72

Sickle cell

AR

73

Sphingolipidoses

AR (except Fabry's - X-linked)

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Thalassemias

AR

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Bruton's agammaglobulinemia

X-linked recessive

76

Wiskott-Aldrich

X-linked recessive

77

Fabry's

X-linked recessiv

78

G6PD

X-linked recessive

79

Ocular albinism

X-linked recessive

80

Lesch-Nyhan

XR

81

Duchenne's and Becker's MD

XR

82

Hunter's Syndrome

XR

83

Hemophilia a and b

XR

84

Robertsonian translocation

13, 14, 15, 21, 22; long arms of two acrocentric chromosomes fuse at centromere. Can be balanced or cause trisomy

85

Microdeletion

cri du chat = short arm of 5. microcephaly, retardation, high pitched crying, epicanthal fold, VSD; Williams syndrome = microdeletion on Chr 7, elfin facies, retardation, hypercalcemia (high vit D sensitivity), well developed verbal skills, extreme friendliness with strangers