Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

My MOD 1 > Genetics > Flashcards

Genetics Flashcards

1
Q

3 categories of genetic DOs

A

mutation in a single gene with large effects (Mendelian DOs)
chromosomal DOs
Complex multigenic DOs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Mendelian DOs

A

rare, high penetrance

Sickle cell anemia: strong selective forces (malaria) maintain mutation in population

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Chromosomal DOs

A

structural or numerical alterations in autosomes and sex chromosomes
uncommon
high penetrance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Complex multigenic DOs

A

more common
Low penetrance
environment and gene interactions (aka polymorphisms)
no single gene necessary or sufficient to produce disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Examples of complex multigenic DOs

A

atherosclerosis, diabetes, hypertension, autoimmune diseases, ht and wt

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Mutation

A

permanent change in the DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Germ cell mutations give rise to

A

inherited disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Somatic cells give rise to

A

cancer and some congenital malformations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Point mutations within coding sequence

A

Missense: alter meaning of sequence of encoded protein (sickle cell–>Glu to Val)
Nonsense: stop codon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Mutations in non-coding sequences

A

promotor or enhancer sequences
defective splicing of intervening sequences
no translation
transcription factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

3 most common transcription factors

A

MYC, JUN, p53

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Deletions and insertions

A

if multiple of 3, reading frame is intact–>abnormal protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Frameshift mutation

A

deletion or insertion not in a multiple of 3–>altering of reading frame

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Trinucleotide repeat

A

amplification of a sequence of 3 nucleotides

almost all contain guanine and cytosine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Anticipation

A

a genetic disorder is passed on to the next generation, the symptoms become apparent at an earlier age with each generation
increase in severity of symptoms
Huntington’s disease, myotonic dystrophy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Mendelian disorders

A

every individual is a carrier of 5-8 deleterious genes, most are recessive and no serious phenotypic effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Codominance

A

both alleles contribute to phenotype

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Pleiotropism

A

single mutant gene–>many end effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Genetic heterogeneity

A

mutations at several loci may produce the same trait

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Autosomal dominant (AD) DOs

A

manifest in the heterozygous state (only one gene affected) so 1 parent is usually affected

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

New mutations in AD DOs

A

seem to occur in germ cells of relatively older fathers

if disease decreases reproductive fitness, then most cases would have to be from new mutations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Incomplete penetrance

A

positive mutation but normal phenotype

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Variable expressivity

A

all positive traits, but expressed differently

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Example of variable expressivity

A

Neurofibromatosis type 1: can have or not have cafe-au-lait spots, skeletal deformities, and/or neurofibromas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

decreased product, dysfunctional or inactive protein produced in AD DOs

A

Loss of function mutations: familial hypercholesterolemia

Gain of function mutations: huntingtin protein toxic to neurons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

2 main patterns of disease with AD

A

regulation of complex metabolic pathways, subject to feedback inhibition
key structural proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

LDL receptor in familial hypercholesterolemia

A

50% reduction in receptor–>secondary increase in cholesterol–>atherosclerosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Key structural proteins affected in AD DOs

A

collagen and cytoskeletal elements of the RBC membrane (e.g. Spectrin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Osteogenesis imperfecta

A

mutant allele can interfere with assembly of functionally normal multimer
AD DO

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Age of onset for AD DOs

A

delayed; symptoms appear in adulthood (30s-50s)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Pedigree for AD

A

every generation
equally male and female overall
50/50 chance of getting it every generation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Examples of AD disorders

A 
Huntington's disease
neurofibromatosis
Marfan syndrome
Ehlers-Danlos syndrome
Osteogenesis imperfecta
Familial hypercholesterolemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Examples of AR disorders

A 
cystic fibrosis
phenylketonuria
lysosomal storage diseases
glycogen storage diseases
Sickle cell anemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Pedigree in AR disorders

A

Skips generations
affects males and females equally
both males and females can be carriers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

AR DOs

A

largest

both alleles are mutated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

3 features of AD DOs

A

trait usually NOT affect parents
siblings have 1/4 chance of having trait
if mutation is of low frequency in population, strong likelihood proband product of consanguineous marriage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Differentiation between AR and AD

A

similar trait/phenotype in AR
complete penetrance common
onset EARLY IN LIFE
new mutations rarely detected clinically
many mutations involve enzymes–>inborn errors of metabolism
decreased normal enzyme of defective enzyme

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Cystic fibrosis bacterial pathogens

A

Staphylococcus aureaus, Haemophilus influenzae, and Pseudomonas aeruginosa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Primary defect in cystic fibrosis

A

CFTR gene on chromosome 7q31.2

epithelial chloride channel protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What does cystic fibrosis affect (generally)?

A

fluid secretion in exocrine glands and in the epithelial lining of the respiratory, GI, and reproductive tracts
abnormal viscous secretions that obstruct organ passages

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Main consequences of CF

A

chronic lung disease (recurrent infections), pancreatic insufficiency, steatorrhea, malnutrition, hepatic cirrhosis, intestinal obstruction, and male infertility

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

When does CF appear?

A

at any point in life from before birth to much later into childhood or adolescence

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

CF pancreas

A

slightly hyperemic, granular, exaggerated lobulation, rounded edges
cysts, chronic pancreatitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Bronchiectasis

A

airway dilation and scarring of bronchus due to persistent or severe infections
signs/symptoms: cough, purulent sputum, fever

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Emphysema

A

airspace enlargement; wall destruction of acinus due to tobacco smoke
signs/symptoms: dyspnea

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

SI of CF pts

A

meconium ileus: unable to pass a stool within the first 48 hours of birth due to distended SI

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

What is the most common lethal genetic disease that affects Caucasian populations?

A

CF; 1 in 2500 live births

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Who has a higher incidence of respiratory and pancreatic disease as compared with the general population?

A

Heterozygous carriers of CF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Genes other than CFTR modify the frequency and severity of certain organ-specific manifestations such as what?

A

pulmonary manifestations and meconium ileus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Male urogenital abnormalities and CF

A

obstructive azoospermia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

How to test for CF?

A

sweat chloride test–>infant will taste salty to the mother

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Phenylketonuria (PKU)

A

Scandinavian descent; NOT AA or Jewish
AR
phenylalanine hydroxylase (PAH) deficiency–>too much phenylalanine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

What does PAH convert phenylalanine to?

A

tyrosine

tyrosine is a precursor for melanin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

When does PKU present?

A

6 months

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

Signs and symptoms of PKU

A

severe MR, hypopigmentation of hair and skin, eczema

musty/mousy odor of urine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

Treatment of PKU

A

dietary restrictions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

Deficiency of what other enzyme besides PAH can give rise to PKU?

A

DHPR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

X-linked Recessive DOs

A

Duchenne muscular dystrophy
glucose-6-phosphate dehydrogenase deficiency
Fragile X syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

Affects on males of X-linked recessive DOs

A

infertility, hence no Y-linked inheritance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

What is the affect on women with X-linked recessive DOs?

A

all daughters of affected males are carriers

heterozygous female not express full phenotypic change because of normal paired allel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

Pedigree for X-linked recessive DOs

A

all males; skipping generations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

Mitochondrial inheritance

A

all from mom
affected males do not pass it on
all positive females pass it on to every offspring

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

Enzyme defecient mendelian DOs

A

PKU

Tay-Sachs disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

Receptor deficient mendelian DOs

A

familial hypercholesterolemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

Oxygen ion channels-hemoglobin mendelian DO

A

Sickle cell anemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

Oxygen ion channels-CFTR mendelian DO

A

Cystic fibrosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

Extracellular collagen mendelian DOs

A

Ehlers-Danlos syndromes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

Cell membrane mendelian DOs

A

Marfan syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

Mendelian DOs

A

alterations in a single gene–>abnormal product or decreased normal product

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

4 main categories of Mendelian DOs

A

enzyme defects and their consequences
defects in membrane receptors and transport systems
alterations in structure, function, or quantity of non-enzyme proteins
mutations resulting in unusual reactions to drugs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

Enzyme mutations

A

decreased activity or decreased amount of normal enzyme

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

3 major consequences of enzyme mutations

A

accumulation of substrate
precursor, intermediate, or alternative product that is toxic
Decreased amount of end product
failure to inactivate a tissue-damaging substrate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

Example of accumulation of substrate due to enzyme mutation

A

Galactosemia: galactose-1-phosphate uridyltransferase deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

Example of decreased amount of end product due to enzyme mutation

A

Albinism: lack of tyrosinase–> decreased melanin

Lesch-Nyhan: increased intermediate product and their breakdown produces toxins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

Example of failure to inactivate a tissue-damaging substrate due to enzyme mutation

A

alpha1- antitrypsin: unable to inactivate neutrophil elastase in lung–>emphysema

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

Examples of defects in receptors and transport systems leading to mendelian DOs

A

familial hypercholesterolemia: decreased synthesis of decreased function of LDL receptor–>defective transport of LDL into cells–>secondary increase in cholesterol synthesis
CF: Cl- ion transport in exocrine sweat glands, sweat ducts, lungs and pancreas defective

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

Sickle cell disease

A

alteration in structure, function, or quantity of non-enzyme proteins–> defect in structure of globin molecule

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

Thalassemias

A

alterations in structure, functions, or quantity of non-enzyme proteins
mutation in globin gene affects amount of globin chains synthesized

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

Examples of alterations in structure, functions, or quantity of non-enzyme proteins

A

collagen, spectrin, dystrophin, osteogenesis imperfecta, hereditary spherocytosis, muscular dystrophies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

Enzyme deficiencies unmasked after exposure to drug

A

G6PD deficiency: antimalarial primaquine–>severe hemolytic anemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

Marfan syndrome inheritance and genes/chromosomes

A

AD
FBN1 chromosme 15Q21.1
FBN2 chromosome 5q23.31 (less common)
1 in 5,000; 70-85% familial

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

What is defective in Marfan’s?

A

extracellular glycoprotein fibrillin-1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

2 fundamental mechanisms by which loss of fibrillin leads to Marfan’s

A

loss of structural support in microfibril rich CT

excessive activation of TGF-beta signaling

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

Clinical features of Marfan’s

A

Tall, exceptionally long extremities, long fingers and toes, increased flexibility, low lactate levels in lungs, short legs, dolicocephalic (long-headed) with frontal bossing and prominent supraorbital ridges, pectus excavatum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

Ectopia lentis

A

seen in Marfan’s; bilateral subluxation/dislocation of the lens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
86
Q

Usual COD for Marfan’s

A

aortic dissection; can also overall have mitral valve prolapse, dilation of ascending aorta, passive dilation of the aortic valve ring and root of the aorta

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
87
Q

Pt symptoms during aortic dissection

A

tearing feeling in chest or between scapula

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
88
Q

Ehlers-Danlos syndromes (EDS)

A

defect in the synthesis or structure of fibrillar collagen
skin is hyperextensible, joints are hypermobile
skin is stretchable, fragile, and vulnerable to trauma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
89
Q

Gaping defects

A

seen in minor injuries in those with EDS; surgical repair or intervention is difficult due to lack of normal tensile strength

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
90
Q

Normal COD for EDS pts

A

rupture of the colon and large arteries (vascular EDS)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
91
Q

Classic EDS internal complications

A

diaphragmatic hernia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
92
Q

Kyphoscoliosis EDS internal complications

A

ocular fragility with rupture of cornea and retinal detachment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
93
Q

Classic EDS gene defects

A

COL5A1, COL5A2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
94
Q

Vascular EDS gene defects

A

COL3A1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
95
Q

Kyphoscoliosis EDS gene defects

A

lysyl hydroxylase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
96
Q

Familial hypercholesterolemia

A

mutation of receptor for LDL

1 in 500 birth have a 2-3 fold increase in cholesterol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
97
Q

Tendinous xanthomas

A

deposit of cholesterol that looks yellow- seen in familial hypercholesterolemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
98
Q

Risks of increased cholesterol

A

premature atherosclerosis, increased risk of MI

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
99
Q

Are hetero or homozygotes more severely affected in familial hypercholesterolemia?

A

homozygotes: 5-6 fold increase in plasma cholesterol levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
100
Q

Homozygotes in familial hypercholesterolemia risks

A

skin xanthomas, coronary, cerebral, and peripheral vascular atherosclerosis at early age; MI before 20 y.o.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
101
Q

Sign seen in eyes in homozygotes in familial hypercholesterolemia

A

arcus cornelius: deposit of material in cornea; usually seen in older pts but can be seen in young pts with this issue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
102
Q

Mutation class I familial hypercholesterolemia

A

no synthesis of LDL receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
103
Q

Mutation class II familial hypercholesterolemia

A

synthesis, but no transport of LDL receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
104
Q

Mutation class III familial hypercholesterolemia

A

synthesis, transport, but no binding of LDL receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
105
Q

Mutation class IV familial hypercholesterolemia

A

synthesis, transport, binding, but no clustering of LDL receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
106
Q

Mutation class V familial hypercholesterolemia

A

synthesis, transport, binding, clustering, but no recycling of LDL receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
107
Q

Lysosomal storage diseases

A

catabolism of the substrate of the missing enzyme remains incomplete, leading to the accumulation within the lysosomes- primary accumulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
108
Q

Primary accumulation in LSD

A

stuffed with incompletely digested macromolecules, lysosomes become large and numerous enough to interfere with normal cell functions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
109
Q

Secondary accumulation in LSD

A

impaired lysosomal function–>impaired autophagy–>accumulation of autophagic substrates

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
110
Q

3 general approaches to treatment of LSD

A

enzyme replacement therapy
substrate reduction therapy
molecular basis of enzyme deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
111
Q

Primary storage in LSD

A

defective fusion of autophagosome with lysosome

defective degradation of intracellular organelles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
112
Q

Secondary storage in LSD

A

accumulation of toxic proteins

accumulation of aberrant mitochondria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
113
Q

Enzyme deficiency in Tay-Sachs disease

A

Shingolipidoses; hexosaminidase- alpha subunit

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
114
Q

Major accumulating metabolite in Tay-Sachs disease

A

G M2 ganglioside

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
115
Q

Gaucher disease enzyme deficiency

A

Sulfatidoses; glucocerebronsidase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
116
Q

Major accumulating metabolite in Gaucher disease

A

glucocerebroside

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
117
Q

Niemann-Pick diseases: A and B major accumulating metabolite

A

Sulfatidoses; sphingomyelinase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
118
Q

Major accumulating metabolite in Niemann-Pick

A

sphingomyelin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
119
Q

MPS I H (Hurler) disease enzyme deficiency

A

Mucopolysaccharidoses (MPSs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
120
Q

MPS II H (Hunter) disease enzyme deficiency

A

Sulfatidoses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
121
Q

Major accumulating metabolite in MPS I and II

A

dermatan sulfate, heparan sulfate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
122
Q

Tay-Sachs disease

A

GM2 Gangliosidosis: Hexosaminidase alpha-subunit deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
123
Q

What are GM2 gangliosidoses?

A

a group of 3 lysosomal storage diseases caused by an inability to catabolize GM2 gangliosides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
124
Q

Chromosome affected in Tay-Sachs disease

A

mutation in the alpha-subunit locus on chromosome 15–>severe deficiency of Hexosaminidase A

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
125
Q

Ethnic group most affected by Tay-Sachs disease

A

Ashkenazic Jews; carrier rate of 1 in 30

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
126
Q

Age of onset of symptoms of Tay-Sachs disease

A

6 months motor and mental deterioration; obtunded, flaccidity, blindness, and dementia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
127
Q

Affect of Tay-Sachs disease

A

1-2 yo vegetative state; death by age 2-3 yo

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
128
Q

Classic sign for Tay-Sachs disease

A

cherry red spot in the macula: ganglion cells of retina swollen, especially around macula

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
129
Q

GM2 ganglioside accumulates where?

A

neurons, retina, heart, liver, spleen

130
Q

Fat stains on what are positive in Tay-Sachs disease?

A

cytoplasmic inclusions; oil red O and Sudan black B are positive

131
Q

Tay-Sachs disease on stains

A

see whorled lysosomes and lipid vacuoles in neuron cytoplasm

132
Q

Niemann-Pick disease, types A and B

A

lysosomal accumulation of sphingomyelin due to inherited deficiency of sphingomyelinase

133
Q

Inheritance of Niemann-Pick disease

A

AR, Ashkenazi Jews, Chromosome 11p15.4–>maternal chromsome

134
Q

Type A Niemann-Pick disease

A

severe infantile form; complete lack of sphingomyelinase; extensive neuro involvement, visceral accumulations of sphingomyelin; progressive wasting

135
Q

Symptoms onset and death for Type A Niemann-Pick disease

A

symptoms by 6 months; death before 3 yo

136
Q

Type B Niemann-Pick disease

A

organomegaly, NO CNS involvement; reach adulthood

137
Q

Type C Niemann-Pick disease

A

most common, NPC1 (95%), transport free cholesterol from lysosomes to cytoplasm

138
Q

Symptoms of Type C Niemann-Pick disease

A

progressive neuro damage; ataxia, vertical supranuclear gaze palsy, dystonia, dysarthria, psychomotor regression

139
Q

Morphology of cells in Niemann-Pick disease

A

enlarged due to sphingomyelin and cholesterol accumulation; foamy cytoplasm; zebra bodies

140
Q

Zebra bodies

A

Niemann-Pick disease; lysosomes with concentric lamellations (EM)

141
Q

Distinguishing factor of Niemann-Pick disease

A

massive splenomegaly; accumulation in spleen, liver, LN, BM, tonsils, GI tract, lungs
1/3-1/2 have cherry red spots in retina; vacuolation and ballooning of neurons, brain atrophy

142
Q

Gaucher disease

A

Glucocerebrosidase mutation
accumulation of glucocerebroside in phagocytes primarily, CNS also
damage due to accumulation and activation of macrophages

143
Q

Cytokines released when macrophages are activated

A

IL-1, IL-6, and TNF

144
Q

Inheritance of Gaucher disease

A

AR

145
Q

Most common lysosomal storage DO

A

Gaucher disease

146
Q

Type I Gaucher disease

A

chronic; 90% of cases; European Jews; NO CNS involvement, spleen and bone symptoms, slight decrease in life span

147
Q

Type II Gaucher disease

A

acute neuronopathic: infantile cerebral pattern, progressive CNS involvement, early death, hepatosplenomegaly; NOT JEWISH

148
Q

Type III Gaucher disease

A

Intermediate; systemic involvement with progressive CNS disease that begins in adolescence or early adulthood

149
Q

Morphology of Gaucher disease

A

distended phagocytic cells- Gaucher cells in liver, spleen, BM, LN, tonsils, thymus, and Peyer’s patches
fibrillary type cytoplasm–> crumpled tissue paper

150
Q

Distinguishing factor of Gaucher disease

A

Enlarged spleen–> >10kg; pancyotpenia or thrombocytopenia (BM)

151
Q

Treatment of Gaucher disease

A

allogenic hematopoietic stem cell transplant; recombinant enzyme

152
Q

Mucopolysaccharidoses (MPS)

A

deficient enzymes degrading glycosaminoglycans

Mucopolysaccharides abundant in ground substance of CT

153
Q

MPS abundant in CT

A

dermatan sulfate, heparan sulfate, keratan sulfate, and chondroitin sulfate

154
Q

Inheritance of MPS

A

All AR except Hunter syndrome–>X-linked recessive

155
Q

Clinical features of MPS

A

coarse facial features, clouding of the cornea, joint stiffness, MR

156
Q

Hurler syndrome

A

MPS I-H: normal at birth, hepatosplenomegaly by 6-24 months, death 6-10 yo

157
Q

COD for Hurler syndrome

A

Cardiovascular complications: coronary arterial and valvular deposits; growth retardation, coarse facial features, skeletal abnormalities

158
Q

Hunter syndrome

A

MPS II; X-linked; NO corneal clouding, milder clinical course

159
Q

Distinguishing factor between Hurler and Hunters

A

No corneal clouding–>Hunters

Corneal clouding–>Hurlers

160
Q

Where are mucopolysaccharides found?

A

Mononuclear phagocytic cells, endothelial cells, intimal SM cells, fibroblasts

161
Q

Balloon cells

A

clear cytoplasm, multiple vacuoles- swollen lysosomes PAS

162
Q

MPS morphology

A

balloon cells, lamellated zebra bodies

163
Q

Common clinical features to all MPSs

A

hepatosplenomegaly, skeletal deformities, valvular lesions, and subendothelial arterial deposits, and brain lesions

164
Q

COD for MPS

A

MI and cardiac decompensation

165
Q

Hepatic type of Glycogenoses

A

Hepatorenal- von Gierke disease (Type I)

166
Q

Morphological changes in von Gierke disease

A

hepatomegaly-accumulations of glycogen and small amounts of lipid; intranuclear glycogen
Renomegaly- accumulation of glycogen in cortical tubular epithelial cells

167
Q

Clinical features of von Gierke disease

A 
failure to thrive if untreated; hepatosplenomegaly and renomegaly
Hypoglycemia
Hyperlipidemia and hyperuricemia
gout and skin xanthomas
bleeding tendency
168
Q

Miscellaneous type of Glycogenoses

A

Pompe disease (Type II)

169
Q

Enzyme deficiency in von Gierke disease

A

glucose-6-phosphatase

170
Q

Enzyme deficiency in Pompe disease

A

lysosomal glucosidase (acid maltase)

171
Q

Morphological changes in Pompe disease

A

mild hepatomegaly
lacy cytoplasmic patterns in lysosomes
cardiomegaly-glycogen in sarcoplasm
skeletal M. similar to changes in heart

172
Q

Clinical features of Pompe disease

A

Major cardiomegaly
muscle hypotonia
cardiorespiratory failure within 2 years
milder adult form with only skeletal muscle involvement, presenting with chronic myopathy

173
Q

Can you survive von Gierke’s disease if treated?

A

Yes, develop late complications

174
Q

Glycogen storage diseases

A

Glycogenoses

hereditary deficiency of one of the enzymes involved in the synthesis or sequential degradation of glycogen

175
Q

Result of glycogen storage diseases

A

storage of normal or abnormal forms of glycogen, predominantly in the liver or muscle

176
Q

3 major subgroups of GSD

A

Hepatic forms
Myopathic forms
Miscellaneous

177
Q

Hepatic form of GSD

A

von Gierke type I: Glucose-6-phosphatase deficiency
liver key to glycogen metabolism; increase of storage of glycogen in liver and decreased blood glucose concentrations (hypoglycemia)

178
Q

Myopathic form of GSD

A 
skeletal muscle; increased glycogen storage in muscle and muscle weakness; muscle cramps after exercise, no increase in blood lactate after exercise due to block
McArdle disease (type V): muscle phosphorylase deficiency
179
Q

Miscellaneous GSD

A 
deficiency of glucosidase (acid maltase) and lack of branching enzyme 
Pompe disease (type II): acid maltase deficiency-->cardiomegaly
associated with glycogen storage in many organs and death early in life
180
Q

Morphology of Pompe Disease

A

glycogen filled myocardial cells

181
Q

Multifactorial inheritance

A

environmental influences with two or more genes affected

most common genetic cause of congenital malformations

182
Q

Common malformations for multifactorial inheritance

A

cleft lip, cleft palate, and neural tube defects (folic acid)

183
Q

What can reduce the incidence of neural tube defects?

A

periconceptional intake of folic acid in diet

184
Q

A range of levels of severity of a disease is suggestive of what?

A

a complex multigenic disorder

185
Q

Variable expressivity and reduced penetrance can be found also in what types of mutations?

A

single mutant genes

186
Q

What makes it difficult to distinguish between Mendelian and multifactorial disease?

A

Variable expressivity and reduced penetrance seen in both complex multigenic disorders and single mutant genes

187
Q

Chromosomal DOs

A

Euploid, aneuploid, monosomy, mosaicism

188
Q

Euploid

A

any exact multiple of haploid number (23)

189
Q

Aneuploid

A

NOT an exact multiple of 23

190
Q

Nondisjunction

A

aneuploidy; gametogenesis, gametes have +/- 1 chromosome

191
Q

Anaphase lag

A

Aneuploidy; during either meiosis or mitosis one chromatid lags behind and is left out of the cell nucleus–>one normal cell and one monosomy cell

192
Q

Monosomy involving an autosome causes…

A

loss of too much genetic info to permit live birth or even embryogenesis

193
Q

Do several autosomal trisomies permit survival?

A

Yes

194
Q

Mosaicism

A

mitotic errors in early development give rise to two or more populations of cells with different chromosomal complement, in the same individual
can affect sex chromosomes

195
Q

Ring chromosome

A

break occurs at both ends of a chromosome with fusion of the damaged ends
e.g. 46 XY, r (14)

196
Q

Inversion

A

rearrangement that involves 2 breaks within a single chromosome with reincorporation of the inverted intervening segment

197
Q

Paracentric inversion

A

inversion involving only one arm of the chromosome

198
Q

Pericentric inversion

A

breaks are on opposite sides of the centromere

199
Q

Isochromosome

A

one arm of a chromosome is lost, remaining arm is duplicated, resulting in a chromosome consisting of 2 short arms only or 2 long arms only

200
Q

Translocation

A

segment of one chromosome is transferred to another one

201
Q

Balanced reciprocal translocation

A

single breaks in each of 2 chromosomes, with exchange of material; NO LOSS of material, likely normal phenotype

202
Q

Robertsonian translocation

A

centric fusion; translocation between 2 acrocentric chromosomes; typically breaks appear closer to the centromeres of each chromosome

203
Q

Resulting chromosomes in Robertsonian translocation

A

1 very large chromosome and 1 extremely small one

small one is usually lost, but because it carries only highly redundant genes–>normal phenotype

204
Q

Prevalence of Robertsonian translocation

A

1 in 1000

205
Q

Trisomy 21

A

3-4% caused by Robertsonian translocation
q arm of chromosome 21 is translocated onto another chromosome–>46 chromosomes, but 3 copies of the long arm of chromosome 21, which carries all of the functional genes of this chromosome

206
Q

Clinical features trisomy 21

A

flat facial profile, oblique palpebral fissures, pericanthal folds, brushfield spots on iris, short, broad hands with simian crease, wide gap between first and second toes

207
Q

Trisomy 21 (Down Syndrome)

A

most common chromosomal DO; major cause of MR; 47 chromosomes

208
Q

Incidence of Down Syndrome

A

1 in 700; maternal age strong influence

209
Q

1% of Down syndrome pts are…

A

mosaics, mixture of cells with either 46 or 47 chromsomes

210
Q

COD Down Syndrome

A

40% of pts have congenital heart disease

include AV septal defects, AV valve malformations, ventricular septal defects, ostium primum

211
Q

Pts with Down Syndrome have a 10 to 20-fold increased risk in developing what?

A

Acute leukemia

212
Q

Pts over 40 with Down Syndrome develop changes characteristic to what disease?

A

Alzheimer disease

213
Q

Down syndrome and immunity

A

abnormal immune responses that predispose them to serious infections, particularly of the lungs and thyroid

214
Q

Trisomy 18

A 
Edwards syndrome
1 in 8000 births
micrognathia
overlapping fingers
renal malformations
rocker-bottom feet
215
Q

Trisomy 13

A 
Patau syndrome
1 in 15,000
cleft lip and palate, polydactyly
microphtlamia
umbilical hernia
renal defects
rocker-bottom feet
216
Q

Chromosome 22q11.2 deletion syndrome

A

congenital heart defects, abnormalities of the palate, facial dysmorphism, developmental delay, T-cell immunodeficiency and hypocalcemia
Incidence: 1 in 4000

217
Q

DiGeorge syndrome

A

Chr 22q.11.2 deletion syndrome
thymic hypoplasia, with resultant T-cell immunodeficiency, parathyroid hypoplasia–>hypocalcemia, cardiac malformations, and mild facial anomalies
CATCH 22

218
Q

Velocardiofacial syndrome

A

Chr 22q.11.2 deletion
eyes: narrow palpebral fissures, puffy lids
ears: over-folded helix and attached lobule
Nose: pear-shaped; square nasal bridge
cleft palate, cardiovascular anomalies, learning disabilities

219
Q

CATCH 22

A 
DiGeorge Syndrome
Cardiac abnormality
Abnromal facies
Thymic aplasia
Cleft palate
Hypocalcemia/hypoparathyroidism
220
Q

Sex Chromosome DOs

A

genetic diseases associated with changes involving the sex chromosomes
more common than autosomal aberrations

221
Q

Imbalances of sex chromosomes vs. autosome imbalances

A

much better tolerated than are similar imbalances of autosomes

222
Q

2 factors that are peculiar to the sex chromosomes

A

lyonization or inactivation of all but one X chromosome

the modest amount of genetic material carried by the Y chromosome

223
Q

Lyon hypothesis

A

only 1 X chromosome is genetically active; other one undergoes heteropyknosis–>inactive
inactivation of the other X chromosome is random during blastocyst stage
inactivation of the same X chromosome persists in all cells derived from each precursor cell

224
Q

Normal females are in reality what genetically?

A

Mosaics and have two populations of cells, one with an inactivated maternal X and the other with an inactivated paternal X

225
Q

Barr body

A

inactive X that can be seen in the interphase nucleus as a darkly staining small mass in contact with the nuclear membrane

226
Q

Lyonization

A

X-inactivation–>Barr body produced

227
Q

What determines the male sex?

A

the presence of a single Y

228
Q

What do sex chromosome disorders lead to?

A

subtle, chronic problems relating to sex development and fertility

229
Q

When are sex chromosome disorders diagnosed?

A

Difficult at birth, usually at puberty

230
Q

The greater the number of (blank), the greater the likelihood of (blank)

A

the number of X chromosomes; mental retardation

231
Q

Klinefelter syndrome

A

47, XXY

male hypogonadism when greater than 2X or greater than 1Y

232
Q

Incidence of Klinefelter syndrome

A

1 in 660 live male births–>hypogonadism diagnosed after puberty

233
Q

Clinical findings in Klinefelter’s

A

eunuchoid body habitus with abnormally long legs, small atrophic testes and small penis; gynecomastia; lower IQ
deep voice, beard, and male distribution of pubic hair

234
Q

Pts with Klinefelters have an increased risk of what other diseases?

A

Type 2 DM and metabolic syndrome; 50% mitral valve prolapse; osteoporosis and fractures due to hormone imbalance

235
Q

How does Klinefelter syndrome cause male infertility?

A

reduced spermatogenesis

236
Q

Those with Klinefelter’s have 20x increased risk of developing what diseases?

A

Breast; extragonadal germ cell tumors, and autoimmune diseases such as SLE

237
Q

Turner Syndrome

A

45X

complete or partial monosomy of X chr, characterized primarily by hypogonadism in phenotypic females

238
Q

Karyotypes in Turner syndrome

A

45, X/46 XX;
45, X/46XY
45, X/47,XXX

239
Q

Incidence of Turner syndrome

A

1 in 2500; most common sex chromosome abnormality in females

240
Q

3 types of karyotypic abnormalities in Turner syndrome

A

57% are missing an entire X chromosome–>45, XO karyotype
common feature is to produce partial monosomy of X chromosome
mosaic pts have a 45, X cell population plus more than one karyotypically normal or abnormal cell type

241
Q

Cystic hygroma

A

infant with edema–>swelling of the nape of the nneck due to lymph stasis
swellings subside but leave bilateral neck webbing and persistent looseness of skin on the back of the neck
related to Turner Syndrome

242
Q

Turner syndrome and congenital heart disease

A

25-50% of pts; left-sided CV abnormalities, preductal coarctation of the aorta and bicuspid aortic valve

243
Q

COD in children with Turner syndrome

A

CV abnormalities

244
Q

Clinical features of Turner

A

shortness of stature, amenorrhea, webbing of neck, cubitus valgus, CV malformations, lack of secondary sex characteristics, fibrotic ovaries, widely spaced nipples

245
Q

Most important cause of primary amenorrhea

A

Turner syndrome

246
Q

Menopause before menarche

A

Turner syndrome

ovaries are decreased atrophic fibrous strands, devoid of ova and follicles–>streak ovaries

247
Q

Turner syndrome and the thyroid

A

develop autoantibodies that react with the thyroid gland; less than half develop hypothyroidism

248
Q

Metabolic affects in some Turner syndrome pts

A

glucose intolerance, obesity, insulin resistance

249
Q

Hermaphroditism

A

the presence of both ovarian and testicular tissue

250
Q

Pseudohermaphrodite

A

disagreement between the phenotypic and gonadal sex

251
Q

Female pseudohermaphrodite

A

has ovaries, but male external genitalia

252
Q

Male pseudohermaphrodite

A

has testicles, but female-type genitalia

253
Q

4 categories of single-gene disorders with nonclassical inheritance

A

trinucleotide-repeat mutatoins
mutations in mitochondrial genes
genomic imprinting
gonadal mosaicism

254
Q

Trinucleotide repeat DOs

A

Fragile X syndrome

Huntington disease

255
Q

Expansions affecting noncoding regions

A

Fragile X syndrome

256
Q

Expansions affecting coding regions

A

Huntington’s disease

257
Q

Trinucleotide-repeat mutations

A

expansion of trinucleotide repeats–>neurogenerative disorders

258
Q

The expansion of a stretch of trinucleotides usually share what nucleotides?

A

G and C

259
Q

What does the proclivity to expand in TNR mutations depend on?

A

sex of the transmitting parent

260
Q

3 key mechanisms by which unstable repeats case diseases

A

Loss of function
Toxic gain of function
Toxic gain of function mediated by mRNA

261
Q

Example of loss of function due to TNR mutations

A

Fragile X syndrome
non-coding
transcription silencing

262
Q

Example of toxic gain of function due to TNR mutations

A

alteration of protein structure
Huntington disease and spinocerebellar ataxias
coding regions

263
Q

Example of toxic gain of function mediated by mRNA due to TNR mutations

A

fragile X tremor-ataxia syndrome

noncoding part of gene

264
Q

Morphological hallmark of TNR mutations

A

accumulation of aggregated mutant proteins in large intranuclear inclusions

265
Q

Fragile X Syndrome

A

second most common genetic cause of MR (Down’s #1)
trinucleotide mutation in the familial mental retardation-1 (FMR1)
CGG repeats–> 200-4000

266
Q

When does loss of function of the FMR protein occur? (transcriptional silencing)

A

trinucleotide repeats in the FMR1 gene exceed 230–>leads to abnormal methylation of gene

267
Q

Incidence of Fragile X syndrome

A

1 in 1550 for males, 1 in 8000 for females

268
Q

Clinical features of Fragile X syndrome

A

males–>MR; long face with a large mandible, large everted ears, large testicles (macro-orchidism), hyperextensible joints, high arched palate, mitral valve prolapse

269
Q

Most distinctive feature of Fragile X syndrome

A

macro-orchidism (large testicles)

270
Q

Carrier males in Fragile X syndrome

A

20% of males who are clinically and cytogenetically normal
carrier males transmit the trait through all their phenotypically normal daughters to affected grandchildren
called normal transmitting males

271
Q

What happens to the # of TNR when carrier males pass to their progeny?

A

small changes in repeat number

272
Q

What happens to the # of TNR when carrier females pass to their progeny?

A

dramatic amplification of the CGG repeats–>MR in most male offspring and 50% of female offspring

273
Q

Premutations of TNR in Fragile X syndrome can be converted via what during the process of what?

A

converted to mutations by triplet-repeat amplification in oogenesis, not spermatogenesis

274
Q

Affected females of Fragile X syndrome

A

30-50% of carrier females are affected

much higher than that in other X-linked recessive disorders

275
Q

Risk of phenotypic effects of Fragile X syndrome

A

risk depends on the position of the individual in the pedigree
Ex: brothers of transmitting males are at a 9% risk, but grandsons are at a 40% risk

276
Q

Anticipation of Fragile X syndrome

A

Clinical features of fragile X syndrome worsen with each successive generation, as if the mutation becomes increasingly deleterious as it is transmitted from a man to his grandsons and great-grandsons

277
Q

Huntington Disease (HD)

A

AD disease

progressive movement disorders and dementia, caused by degeneration of striatal neurons

278
Q

HD is the prototype of what diseases?

A

polyglutamine trinucleotide repeat

279
Q

Gene, chromosome, and protein affected in Huntington’s disease

A

HTT, 4p16.3, huntingtin

280
Q

Fatality of Huntington’s disease

A

Average about 15 years after diagnosis

281
Q

Anticipiation of Huntington’s disease

A

repeat expansions during spermatogenesis, so the paternal transmission is associated with early onset in the next generation

282
Q

Mutations in mitochondrial genes

A

ova contain numerous mitochondria; spermatozoa contain a few

mtDNA complement of the zygote is only from ovum

283
Q

Transmission of mtDNA

A

mothers–>all offspring

daugthers, not sons, transmit the DNA further to their progeny

284
Q

Heteroplasmy

A

tissues and individuals harbor both wild-type and mutant mtDNA

285
Q

Threshold effect

A

minimum number of mutant mtDNA must be present in a cell or tissue before oxidative dysfunction gives rise to disease

286
Q

Prototype of mtDNA disorder

A

Leber hereditary optic neuropathy

287
Q

Leber hereditary optic neuropathy

A

neurodegenerative disease that manifests as a progressive bilateral loss of central vision
first noted between 15-35 yo
eventual blindness

288
Q

Genomic imprinting

A

imprinting selectively inactivates either the maternal or paternal allele

289
Q

Maternal imprinting

A

transcriptional silencing of the maternal allele

290
Q

Paternal imprinting

A

paternal allele is inactivated

291
Q

When does imprinting occur?

A

in ovum or sperm before fertilization and then is stably transmitted to all somatic cells through mitosis

292
Q

Deletions in genomic imprinting

A

gene or set of genes on maternal chromosome 15q12 is imprinted (silenced)
only functional alleles are provided by the paternal chromosome
70% of cases

293
Q

Uniparental disomy

A

Prader-Willi syndrome
two maternal copies of chromosome 15
20-25% of cases

294
Q

Defective imprinting

A

1-4% of pts
some pts with Prader-Willi–>paternal chromosome carries the maternal imprint
Angelman syndrome–>maternal chromosome carries the paternal imprint
both lead to no functional alleles

295
Q

Prader-Willi syndrome

A

Paternal deletion

MR, short stature, hypotonia, profound hyperphagia, obesity, small hands and feet, hypogonadism

296
Q

Gene and chromosome affected in Prader-Willi

A

chr 15, del(15)(q11.2.q13)

297
Q

Angelman syndrome

A

Maternal deletion

born with a deletion of the same chromosomal region derived from their mothers

298
Q

Clinical features of Angelman

A

MR, ataxic gait, seizures, inappropriate laughter

happy puppets

299
Q

Indications for prenatal testing for cytogenic abnormalities

A

advanced maternal age
parent known to carry a balanced chromosomal rearrangement
fetal anomalies observed on US
routine maternal blood screening, indicating an increased risk of Down Syndrome or another trisomy

300
Q

Genetic analysis in the diagnosis and treatment of cancer

A

detection of tumor-specific acquired mutations and cytogenic alterations that are hallmarks of specific tumors
determination of clonality as an indicator of a neoplastic condition
ID of specific genetic alterations that can direct therapeutic choices
determination of a treatment efficacy
detection of drug-resistant secondary mutations in malignancies treated with genetically tailored therapeutics

301
Q

Diagnosis and management of infectious disease

A

detection of microorganism-specific genetic material for definitive diagnosis
ID of a specific genetic alterations in the genomes of microbes that are associated with drug resistance
determination of treatment efficacy

302
Q

What cells are used for prenatal testing?

A

obtained by amniocentesis, chorionic villus biopsy, or umbilical cord blood
as much as 10% of the free DNA in a pregnant mother’s blood is of fetal origin–>noninvasive diagnostics utilizing this source of DNA

303
Q

How is testing after birth performed?

A

peripheral blood DNA and is targeted based on clinical suspicion

304
Q

When to suspect a genetic syndrome

A

the presence of one obvious malformation should not limit the full evaluation, because additional, more subtle finding will often be important in that differential diagnosis

305
Q

VATER association

A 
when to suspect a genetic syndrome
vertebral
anal anomalies
cardiac (VACTERL)
treacheo-esophageal fistula
renal anomalies
limb anomalies
306
Q

When is real-time PCR used?

A

monitor the frequency of cancer cells bearing characteristic genetic lesions in the blood or in the tissues or the infectious load of certain viruses

307
Q

What is used to detect somatic point mutations in oncogenes?

A

real-time PCR

KRAS and BRAF

308
Q

Fluorescence in Situ Hybridization (FISH)

A

uses DNA probes that recognize sequences specific to particular chromosomal regions

309
Q

What is FISH used to detect?

A

abnormalities of chromosomes (aneuploidy) or complex translocations that are not demonstrable by routine karyotyping
gene amplification

310
Q

What to submit for FISH

A

prenatal sample (amniotic fluid or chorionic villi)
peripheral blood
cytology material (touch prep)
Formalin fixed paraffin embedded tissue

311
Q

Genomic array technology

A

detects genomic abnormalities
test DNA and normal DNA are labeled with two different fluorescent dyes
differentially labeled samples are co-hybridized to an array spotted with DNA probes that span the human genome at regularly spaced intervals

312
Q

Repeat-length polymorphisms

A

short repetitive sequences of DNA give rise to these; divided based on their length

313
Q

Minisatellites

A

10-100 base pairs; repeat-length polymorphisms

314
Q

Microsatellites

A

1-9 bp; repeat-length polymorphisms

315
Q

Epigenetics

A

the study of heritable chemical modification of DNA or chromatin that does not alter the DNA sequence itself

316
Q

Example of epigenetic alterations

A

methylation of DNA and the methylation and acetylation of histones

317
Q

What diseases involve methylation?

A

Fragile X syndrome, Prader-Willi, and Angelman syndromes

318
Q

RNA analysis

A

HIV and Hepatitis C

mRNA expression profiling–>breast cancer

319
Q

Assays to detect genetic polymorphisms are important to determine what?

A

relatedness and identity in transplantation, cancer genetics, paternity testing, and forensic medicine

320
Q

Genome-Wide Analysis

A

large cohorts of pts with and without a disease are examined across the entire genome for common genetic variations or polymorphisms that are overrepresented in pts with the disease

321
Q

Next-generation sequencing (NGS)

A

newer DNA sequencing technologies that are capable of producing large amounts of sequence dataa in a massively parallel manner

322
Q

Clinical application of NGS

A

targeted sequencing–>common genetic diseases or cancers
whole exome sequencing–>looks at the 1.5% of genome that is encoding protein
Whole genome sequencing-cancers
Standard of care in lung cancers

My MOD 1 (13 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions