1A: Dt 10 - 3

Front 1

How does molecular weight affect gel electrophoresis?

Back 1

Heavier molecules will stay near wells (cathode (-) end), whereas lower weight molecules will move toward anode (+) end.

Front 2

Southern blot:
Utility

Back 2

DNA probe allows for identification (via comparison) of a DNA segment

(SNoW DRoP)

Front 3

Northern blot:
Utility

Back 3

RNA probe allows identification (via comparison) of an RNA segment

(SNoW DRoP)

Front 4

Western blot:
Utility

Back 4

Antibody allows identification of a protein

(SNoW DRoP)

Front 5

ELISA:
Utility

Back 5

Tests antigen-antibody reactivity

Determines whether a particular antibody, e.g., anti-HIV, is present in patient's blood sample. Both sensitivity and specificity of ELISA approach 100% but both false-positives and false-negatives do occur.

Front 6

FISH:
Utility

Back 6

Fluorescent DNA or RNA probe binds specific gene of interest; used for specific localization of genes and direct visualization of anomalies (microdeletions)

Front 7

Codominance:
Define
Example

Back 7

Neither of 2 alleles is dominant

Ex: blood group--A, B, AB

Front 8

Variable expression:
Define
Example

Back 8

Nature and severity of phenotype vary among individuals

Front 9

Incomplete penetrance:
Define

Back 9

Not all individuals with mutant genotype show mutant phenotype (may skip generations)

Front 10

Pleiotropy:
Define
Example

Back 10

1 gene has >1 effect on individual's phenotype

Ex: PKU causes MR, hair/skin changes, etc.

Front 11

Imprinting:
Define
Example

Back 11

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

Ex: Prader-Willi and Angelman's Syndromes

Front 12

Anticipation:
Define
Example

Back 12

Severity of dz worsens or age of onset of dz is earlier in succeeding generations

Ex: HD

Front 13

Loss of heterozygosity:
Define
Example

Back 13

If pt inherits or develops mutation in tumor suppressor gene, complementary allele must be deleted/mutated before cancer develops.

Not true of oncogenes

Ex: retinoblastoma

Front 14

Dominant negative mutation:
Define
Example

Back 14

Exerts a dominant effect.

Heterozygote produces nonfnal altered protein that also prevents normal gene product from functioning.

Ex: mutation of Tx factor in its allosteric site.

Non functioning mutant can still bind DNA preventing wild-type Tx factor from binding

Front 15

Linkage disequilibrium:
Define

Back 15

Tendency for certain alleles at 2 linked loci to occur together more often than expected by chance. Measured in populn, not in a family; often varies in diff populns

Front 16

Mosaicism:
Define
Example

Back 16

Occurs when cells in body have different genetic makeup

Can be germ-line mosaic, which may produce dz not carried by parent's somatic cells

Ex: Lyonization--random X inactvtn in females

Front 17

Locus heterogeneity:
Define
Example

Back 17

Mutations at different loci produce same phenotype

Ex: Marfan's syndrome, MEN 2B, homocystinuria; all cause marfanois habitus

Albinism

Front 18

Heteroplasmy:
Define

Back 18

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

Front 19

Uniparental disomy:
Define

Back 19

Offspring receive 2 copies of chromosome from 1 parent and no copies from other parent

Front 20

Prader-Willi Syndrome:
Pathophys
Presentation

Back 20

Chromosomal deletion form paternal allele

Affects both daughters and sons

Presents: hyperphagia, short stature, tantrums, hypogonadism (childhood osteoporosis)

Confirmed with FISH

Front 21

Angelman's Syndrome:
Pathophys
Presentation

Back 21

Deletion of normally active Maternal allele

Presents w/MR, seizures, ataxia, inappropriate laughter (happy puppet)

Front 22

Hardy-Weinberg equations:
Disease prevalence
Allele prevalence

Back 22

Disease prevalence: p^2 + 2pq + q^2 = 1
Where p^2 = homozygous for p allele (same for q^2)
Where pq = heterozygous

Allele prevalence:
p + q = 1 (100% of populn has either p or q alleles)

Front 23

What is the frequency of the BB phenotype and the Bb phenotype if the frequency of allele B is 70%

Back 23

If B = 70% then b = 30%
bc: B + b = 1

p^2 + 2pq + q^2 = 1
p = BB = 0.7
Thus p^2 = 0.49 = 49%

For Bb:
2pq = 2(0.70)(0.30) = 0.42

Front 24

List 3 mitochondrial inheritance defects.

Back 24

Mitohcondrial myopathies
Leber's hereditary optic neuropathy
Leigh's syndrome

Front 25

Ragged-red muscle fibers on biopsy

Back 25

Mitochondrial myopathy (mitochondrial inheritance defect)

Front 26

Subacute sclerosing encephalopathy

Back 26

Leigh syndrome (mitochondrial inheritance defect)

Front 27

Back 27

AD dz showing Anticipation

Front 28

Back 28

Autosomal Dominant dz w/incomplete penetrance

Front 29

What enzyme is deficient in Niemann-Pick Disease?

Back 29

No man picks his nose with his sphinger.

Sphingomyelinase

Front 30

This genetic condition increases risk of berry aneurysms.

Back 30

AD Polycystic Kidney Dz
Marfan's

Front 31

Which AD disease:
Floppy mitral valve
Dissecting aortic aneurysm
Berry aneurysm

Back 31

Marfan's

Front 32

Which AD disease:
Mitral valve prolapse
Liver disease
Berry aneurysm

Back 32

AD Polycystic Kidney Dz

Front 33

Which AD disease:
neural tumors
Pigmented iris hamartomas

Back 33

NF Type I

Front 34

Which AD disease:
Strong association with colon cancer

Back 34

FAP

Front 35

Which AD disease:
MI before age 20

Back 35

Familial hyperchol

Front 36

Which AD disease:
Hemangioblastomas of retina/cerebellum/medulla

Back 36

vonHippel Lindau

Front 37

Which AD disease:
Increased MCHC
Hemolytic anemia

Back 37

Hereditary spherocytosis

Front 38

Which AD disease:
Bilateral acoustic neuromas

Back 38

NF 2

Front 39

Which AD disease:
Facial lesions
Seizure
Cancer risk

Back 39

Tuberous sclerosis

Front 40

Which AD disease:
Caudate atrophy
Dementia

Back 40

HD

Front 41

Which AD disease:
Cystic medial necrosis of aorta

Back 41

Marfan's

Front 42

Which AD disease:
Defect of fibroblast growth factor receptor 3

Back 42

Achondroplasia

Front 43

Cystic fibrosis:
Pathophys
Presentation
Diagnosis
Treatment

Back 43

Defect in CFTR gene

DEfective Cl- channel-->secretion of abnl thick mucus that plugs lungs, pancreas, liver-->recurrent pulm infections (pseudomonas, Staph aureus)
Chronic bronchitis
Bronchiectasis
Panc insufficiency (Malabsorption and steatorrhea)
Meconium ileus in newborns

Also results in infertility in males due to b/l absence of vas deferencs
Fat soluble vit def. (A, D, E, K)
Failure to thrive

Dx: [Cl-] in sweat >60mEq/L

Tx: N-acetylcysteine to loosen mucous plugs

Front 44

Which lyososomal storage disease is a/w renal failure?

Back 44

Fabry's Dz (tx is dialysis)

Front 45

What are the only two X-LINKED RECESSIVE lysosomal storage diseases?

What is the mode of inheritance of the others?

Back 45

Fabry's and Hunter's are X-linked recessive (X marks the spot for a treasure Hunter).

Almost all others are autosomal recessive.

Front 46

What is the most common lysosomal storage disease?

Back 46

Gaucher's Dz

Front 47

Which lysosomal storage disease are a/w an early death --usually before age 3?

Mode of inheritance?

Back 47

Tay Sachs
Niemann-Pick
Krabbe's Dz

AUTOSOMAL RECESSIVE

Front 48

Which lysosomal storage disease is a demyelinating disease?

Back 48

Metachromatic Leukodystrophy (AR)

Front 49

How might corneal clouding and mental retardation help distinguish between the mucopolysaccharidoses?

Back 49

Hurler's: + corneal clouding, + MR
Hunter's - corneal clouding, +MR
Scheie's: + corneal clouding, -MR
I-cell: + corneal clouding, ±MR

Front 50

Which lysosomal disease deficiency:
alpha-L-iduronidase

Back 50

Hurler's
Scheie's (basically a milder form of Hurler's)

Front 51

Which lysosomal disease deficiency:
Iduronate sulfatase

Back 51

Hunter's

Front 52

Which lysosomal disease deficiency:
Arylsulfatase A

Back 52

Metachromatic leukodystrophy

Front 53

Which lysosomal disease deficiency:
alpha-galactosidase A

Back 53

Fabry's

Front 54

Which lysosomal disease deficiency:
Galactocerebsidase

Back 54

Krabbe's

Front 55

Which lysosomal disease deficiency:
beta-glucocerebrosidase

Back 55

Gaucher's (MOST COMMON)

Front 56

Which lysosomal disease deficiency:
Hexosaminidase

Back 56

Tay-Sachs (Sachs-->Sax-->HEXoSAMinidase)

Front 57

Which lysosomal disease deficiency:
Sphingomyelinase

Back 57

Niemann-Pick

Front 58

Which lysosomal disease:
Accumulation of GM2 ganglioside

Back 58

Tay-Sachs

Front 59

Which lysosomal disease:
Accumulation of dermatin sulfate

Back 59

Hurler's
Hunter's
Scheie's

Front 60

Which lysosomal disease:
Common among Ashkenazi Jews

Back 60

Tay Sachs
Niemann-Pick
Some form of Gaucher's

Front 61

Which lysosomal disease:
Crinkled paper cytoplasm

Back 61

Gaucher's

Front 62

What is the differential diagnosis for a cherry red spot on retina?

Back 62

Niemann-Pick
Tay-Sachs
Central retinal artery occlusion

Front 63

Which diseases are X-linked?

Back 63

Fabry's Tale: Duke the Muscular Hunter Brutally Lysed the Albino Gopher without aWAre it was a Fragile Hemophiliac!

Fabry's
Duchenne MD
Hunter Syndrome
Bruton's agammaglobulinemia
Lesch-Nyhan Syndrome
Ocular albinism
G6PD def
Wiskott-Aldrich
Fragile X
Hemophilia

Front 64

Duchenne's MD:
Pathophys
Diagnosis

Back 64

X-linked frame shift mutation-->Dystrophin gene deletion

Accelerated muscle breakdown.

Weakness begins in pelvic girdle mm and progresses superiorly

Pseudohypertrophy!

Dx: Inc'd CPK, muscle biopsy

Front 65

Becker's MD:
Pathophys
Diagnosis

Back 65

Mutated dystrophin gene; less severe than Duchenne's. Onset in adolescence or early adulthood

Dx: Elevated CPK, muscle bx

Front 66

Fragile X Syndrome:
Pathophys (specific gene mutation)
Presentation

Back 66

Familial MR gene 1 mutation (FMR1 gene codes for FMRP--cytoplasmic protein found in brain, testes; goes to axons and dendrites where it's involved in mRNA translation)

Fragile X = eXtra-large testes, jaw, ears

Front 67

Mode of inheritance:
Glycogen Storage Disease

Back 67

AR

Front 68

Mode of inheritance:
Fragile X

Back 68

X-linked recessive

Front 69

Mode of inheritance:
Polycystic Kidney Disease--Adults vs Infants

Back 69

AD--adults
AR--infants

Front 70

Mode of inheritance:
PKU

Back 70

AR

Front 71

Mode of inheritance:
Hereditary spherocytosis

Back 71

AD

Front 72

Mode of inheritance:
Duchenne's MD

Back 72

X-linked recessive

Front 73

Mode of inheritance:
FAP

Back 73

AD

Front 74

Mode of inheritance:
Lesch-Nyhan

Back 74

X-linked recessive

Front 75

Mode of inheritance:
Bruton's agammaglobulinemia

Back 75

X-linked recessive

Front 76

Mode of inheritance:
Huntington's Disease

Back 76

AD

Front 77

Mode of inheritance:
Thalassemia

Back 77

AR

Front 78

Mode of inheritance:
Sickle Cell

Back 78

AR

Front 79

Mode of inheritance:
Wiscott-Aldrich

Back 79

X-linked recessive

Front 80

Mode of inheritance:
Von Recklinghausen's

Back 80

AKA NF-1; AD

Front 81

Mode of inheritance:
Von Hippel Lindau

Back 81

AD

Front 82

Mode of inheritance:
Hemophilia

Back 82

X-linked Recessive

Front 83

Mode of inheritance:
Mucopolysaccharidosis

Back 83

AR

Front 84

Mode of inheritance:
Familial hypercholesterolemia

Back 84

AD

Front 85

Mode of inheritance:
Sphingolipidosis

Back 85

AR

Front 86

Mode of inheritance:
Marfan's

Back 86

AD

Front 87

Mode of inheritance:
Cystic fibrosis

Back 87

AR

Front 88

Mode of inheritance:
Hemochromatosis

Back 88

AR

Front 89

Mode of inheritance:
G6PD deficiency

Back 89

X-linked recessive

Front 90

Down Syndrome:
Genetic Pathophys
Associated Diseases
Quad screen results
Ultrasound results

Back 90

95% due to meiotic nondisjunciton of homologous chromosomes-->Trisomy 21
4% due to Robertsonian translocation

Duodenal atresia, septum primum type ASD, inc'd risk ALL< AD

Quad screen: low AFP, high beta-hCG, low E3, high inhibin A

U/S: Inc'd nuchal translucency

Front 91

What is Robertsonian translocation?

Back 91

Nonreciprocal chromosomal translocation--occurs when long arms of 2 acrocentric chromosomes (chromosomes with centromeres near their ends_ fust at centromere and 2 short arms are lost.

Balanced translocation normally don't cause abnl phenotype.

Unbalanced translocation-->miscarriage, stillbirth, chromosomal imbalance (Down's, Patau's)

Front 92

Edward's vs Patau's Syndrome:
Chromosomes affected
Presentation

Back 92

Edward's = 18; severe MR, rocker bottom feet, micrognathia, low-set ears, clenched hands, prominent occiput, congenital heart Dz. Death within 1 year (Election age = 18)

Patau's syndrome = 13 (puberty at 13): Severe MR, rocker bottom feet, cleft lip/Palate, holoProsencephaly, Polydactyly, congenital heart dz. Deathw ithin 1 year of birth.

Front 93

Cri-du-chat syndrome:
Pathophys
Presentation

Back 93

Congenital microdeletion of short arm of chromosome 5 (46XX, 46XY, 5p-)

Findings: microcephaly, MR, HIGH PITCHED CRYING/MEWING ~kidney

Front 94

Williams Syndrome:
Pathophys
Presentation

Back 94

COngenitcal microdeletion of long arm of chrom 7--deleted region includes elastin gene

Elf facies; MR, hypercalcemia (inc'd sens to vit D), well-dev'd verbal skills, extreme friendliness with strangers

Front 95

What is the probability that a female heterozygous for an X-linked disease will pass it on to her son?

Back 95

If woman has a son, chance is 50%

If don't know sex of child, 25%

Front 96

What is the probability that a female heterozygous for an X-linked recessive disease that mates with a normal male will
have a carrier daughter?

Back 96

If daughter-->50%

If prob daughter that is carrier-->25%

Front 97

What is the probability that a female carrier of an X-linked disease will have a child with that disease
assuming she mates with a normal male?

Back 97

Prob of having son with defect-->25%

Front 98

If aa symbolizes an X-linked recessive disease, what is the likelihood that parents Aa and Aa will have a phenotypically
normal child?

Back 98

Use punnet square: XA, XA; Y by XA; Xa

Get:
XA, XA
XA, Y
XA, Xa
Xa, Y

25% chance having normal child

Front 99

Cystic fibrosis is an autosomal recessive disorder. Two parents that are heterozygous for cystic fibrosis have
a normal, nonaffected child. What is the probability that the child is homozygous normal?

Back 99

Child is normal, obviously can't be homozygous recessive, so chances of being homozygous normal is 1/3 or 33%

Front 100

Upon examination of a pedigree, you note that both males and females are affected with a disease in every
generation. What type of genetic disease is this?

Back 100

AD

Front 101

What is the frequency of the Aa genotype and the AA genotype if the frequency of allele A is 0.9%?

Back 101

Frequency of heterozygote (Aa) = 0.095 or 10%

Frequency of homozygote dominant (AA) = 0.90 or 90%

Front 102

If 49% of a particular population is homozygous for a curly hair gene that is dominant to a straight hair gene,
what percentage of the population has curly hair?

Back 102

P^2 = .49
P = 0.7
Q = 0.3
frequency of straight hair = 0.3
2*0.7*0.3 = 0.42 + 0.49 = 91% populn

Front 103

Which genetic disease:
A/w floppy mitral valve, dissecting aortic aneurysm, berry aneurysm

Back 103

Marfan's

Front 104

Which genetic disease:
A/w mitral valve prolapse, liver disease, berry aneurysms

Back 104

ADPKD

Front 105

Which genetic disease:
Hemangioblastomas of retina/cerebellum/medulla

Back 105

VHL

Front 106

Which genetic disease:
Increased MCHC, hemolytic anemia

Back 106

Hered Spherocytosis

Front 107

Which genetic disease:
Cafe-au lait spots, soft tissue growths

Back 107

NF 1

Front 108

Which genetic disease:
Macroorchidism and autism

Back 108

Fragile X

Front 109

Which genetic disease:
Endocardial cushion defects are common

Back 109

Down's

Front 110

Which genetic disease:
Recurrent pulmonary infections, steatorrhea

Back 110

CF

Front 111

Which genetic disease:
Multiple fractures, easily confused with child abuse

Back 111

OI

Front 112

Which genetic disease:
A/w Alzheimer's after age 35

Back 112

Down's

Front 113

Which genetic disease:
Prone to bilateral acoustic Schwannomas

Back 113

NF 2

Front 114

Which genetic disease:
Excess fibro-fatty tissue deposits amongst muscle

Back 114

Duchenne's MD

Front 115

What test is used to diagnose cystic fibrosis? Which gene is defective?

Back 115

Chloride Sweat Test
Defective CFTR gene

Front 116

What is the difference between Southern Blot, Northern Blot, and Western Blot?

Back 116

Southern:
Sample: DNA, probe: DNA

Northern:
Sample: RNA, probe: DNA

Western:
Sample: protein, probe: Ab

Front 117

Which lysosomal storage disease:
Accumulation of GM2 ganglioside

Back 117

Tay-Sachs

Front 118

Which lysosomal storage disease:
A/w renal failure

Back 118

Fabrey's

Front 119

Which lysosomal storage disease:
Accumulation of dermatin sulfate

Back 119

Mucopolysaccharidoses:
Hurler's
Hunter's
Scheie's

Front 120

Which lysosomal storage disease:
Deficiency in hexosaminidase

Back 120

Tay-Sach's

Front 121

Two pts have the same mutation on chromosome 15 but have different phenotypic expressions. One pt
received the mutation from the father while the other received the mutation from the mother.

What is this
an example of?

Back 121

Imprinting

Front 122

Frequency of CFTR mutation X in pts with cystic fibrosis is 0.1. Cystic fibrosis can be caused by either
mutation X or mutation Yin the CFTR gene.

What percentage of cystic fibrosis pts are homozygotes for
mutation Y?

Back 122

Frequency of allele Y must be 0.9
0.9^2 =81% are homozygous for mutation Y