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Pathology > Ch9: Genetics > Flashcards

Ch9: Genetics Flashcards

1
Q

Disorders related to single gene usually follow what inheritance pattern?

A

Mendelian

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2
Q

Two types of single gene mutations?

A
  1. Mendelian

2. Non-classic inheritance

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3
Q

What is a mutation?

A

Permanent change in DNA of an organism

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4
Q

What is a genome mutation?

A

Loss or gain of whole chromosomes

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5
Q

What is a chromosomal mutation?

A

Structural changes to chromosomes

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6
Q

What are gene mutations?

A

Change at gene level

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7
Q

What are the two categories of gene mutations?

A
  1. Point mutations

2. Frameshift mutation

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8
Q

What are the two types of point mutations?

A
  1. Nonsense mutation

2. Missense mutation

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9
Q

What are the two types of frameshift mutations?

A
  1. Insertions

2. Deletions

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10
Q

Trinucleotide repeat mutations occur within coding or non-coding regions?

A

Both

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11
Q

What is the longest chromosome?

A

Chromosome 1

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12
Q

Which is the shortest chromosome?

A

Chromosome 22

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13
Q

What is a balanced reciprocal translocation?

A

exchange of material between nonhomologous chromosomes

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14
Q

What is a Robertsonian translocation?

A

nonreciprocal translocation involving two homologous (paired) chromosomes or non-homologous chromosome

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15
Q

What is an isochromosome?

A

chromosome that has lost one of its arms and replaced it with an exact copy of the other arm.

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16
Q

What is a paracentric inversion?

A

reversal of the normal order of genes in a chromosome segment involving only the part of a chromosome at one side of the centromere

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17
Q

What is a pericentric inversion?

A

inversions include the centromere and there is a break point in each arm

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18
Q

How does a ring chromosome form?

A

chromosome whose arms have fused together to form a ring

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19
Q

Hemoglobin S is the result of what type of mutation?

A

Point mutation causing a missense mutation

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20
Q

What is the exact change in hemoglobin S?

A

GAG becomes GUG which encodes valine instead of glutamic acid

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21
Q

What type of mutation is beta thalassemia?

A

Point mutation causing a nonsense mutation.

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22
Q

What type of mutation is the ABO O allele?

A

Frameshift mutation from a single base deletion

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23
Q

Hexosaminidase A/Tay Sachs is the result of what?

A

Frameshift mutation caused by four base insertion

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24
Q

Cystic fibrosis is the result of what?

A

Three base deletion that does NOT cause a frameshift

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25
Q

Fragile X syndrome is the result of what?

A

CGG triplet repeat

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26
Q

Friederich ataxia is the result of what?

A

GAA triplet repeat

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27
Q

Huntington’s disease is the result of what?

A

CAG triplet repeat

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28
Q

Myotonic dystrophy is the result of what?

A

CTG repeat

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29
Q

What is myoclonus epilepsy the result of what?

A

12 repeat: CCCCGCCCCGCG

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30
Q

What is a mendelian disorder?

A

Genetic disorder of large effect caused by a single gene mutation

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31
Q

What is the one common X-linked dominant disorder?

A

Vitamin D resistant rickets

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32
Q

3 mendelian disorder types

A
  1. Autosomal dominant
  2. Autosomal recessive
  3. X-linked recessive
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33
Q

Autosomal dominant is a disorder manifested in what genotype?

A

heterozygous

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34
Q

When do autosomal dominant disorders present?

A

Onset delay until adulthood

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35
Q

Can autosomal dominant disorders spontaneously occur in the germline?

A

yes

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36
Q

What modifies the expression of autosomal dominant genotype?

A
  1. Reduced penetrance

2. variable expressivity

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37
Q

What does the mutated gene usually encode for in autosomal dominant?

A

Control points in metabolic pathways

Key structural proteins

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38
Q

Autosomal recessive disorders are manifested only in what genotype?

A

Homozygous state

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39
Q

Siblings in AR disease have what chance of being affected?

Of being carriers?

A

1 in 4 chance of being affected

1 in 2 chance of being a carrier

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40
Q

If a low frequency gene mutation begins to appear, what does this suggest?

A

Population is consanguineous

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41
Q

Which has more uniform expression, autosomal dominant or recessive?

A

Recessive

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42
Q

Is complete penetrance common in AR?

A

Yes

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43
Q

When does onset of autosomal recessive occur?

A

Early in life

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44
Q

Can spontaneous mutations occur of autosomal recessive genes?

A

Yes, but takes awhile to present (several generations)

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45
Q

Autosomal recessive genes usually encode for what?

A

Enzyme

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46
Q

What protects us against a heterozygous autosomal recessive genotype?

A

The normal gene will make enough enzyme to be at functioning level

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47
Q

X-linked recessive disorders require how many abnormal X chromosomes in females?

A

2

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48
Q

X-linked recessive disorders require how many abnormal X chromosomes in males?

A

1

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49
Q

Who transfers the X-linked recessive gene?

A

Heterozygous female

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50
Q

Who receives the X-linked recessive gene?

A

Sons (1 in 2 chance)

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51
Q

What can lead to expression of an x-linked recessive phenotype in females?

A

Lyonization

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52
Q

How does an affected father of an x-linked recessive disorder pass on the mutation?

A

All daughters will be carriers

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53
Q

What is codominance?

A

When two different gene alleles are fully expressed together.

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54
Q

What are examples of codominance? (2)

A
  1. Histocompatibility

2. Blood groups

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55
Q

Codominant Mendelian disorders occur when?

A

When both normal and mutant gene are fully expressed

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56
Q

What are examples of some codominance disorders? (2)

A
  1. Thalassemias

2. Sickle cell anemia

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57
Q

What is penetrance?

A

The measure of how much a Mendelian disorder is phenotypically expressed.

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58
Q

What is it called when all individuals with a mutation express the phenotype?

A

Complete penetrance

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59
Q

What is it called when some affected individuals are phenotypically normal?

A

Reduced penetrance

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60
Q

What is variable expressivity?

A

Degree of phenotypic change seen in affected individuals.

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61
Q

Example of variable expressivity?

A

Neurofibromatosis. Some individuals have cafe au lait macules and some have widespread neural tumors and deformities

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62
Q

What is polymorphism?

A

Existence of more than one normal allele of a gene.

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63
Q

What are examples of polymorphisms? 2

A
  1. histocompatibility genes

2. Blood group genes

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64
Q

What are the most common form of polymorphisms?

A

SNP’s

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65
Q

SNP’s occur in coding regions how often?

A

1%

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66
Q

What is pleiotropism?

A

Ability of a single mutation to have more than one phenotypic effect?

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67
Q

What are two examples of pleiotropism?

A
  1. Marfan syndrome

2. Neurofibromatosis

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68
Q

What is genetic heterogeneity?

A

Ability of different gene muations to cause the same phenotypic change.

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69
Q

Example of genetic heterogeneity? (2)

A
  1. Retinitis pigmentosa

2. Childhood deafness

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70
Q

What is the phenotype?

A

Physical appearance or biochemical characteristics as distinguished from its genotype

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71
Q

What is genotype?

A

genetic makeup of an organism as distinguished from its physical characteristics

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72
Q

Two types of non-protein producing genes?

A
  1. miRNA

2. lcRNA

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73
Q

What are miRNA?

A

small RNA molecules that are further shortened, unwound to single RNA strands, and coupled with proteins.

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74
Q

The RNA-induced silencing complex interacts with what?

To what effect?

A

miRNA

Cleave or suppress translation of mRNA

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75
Q

If child has an autosomal dominant mutation but neither parent does, what happened?

A

Spontaneous mutation

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76
Q

Are autosomal dominant mutations usually loss of function or gain of function?

A

Loss

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77
Q

Two main characterizations of AD disorders?

A
  1. variable expressivity

2. reduced penetrance

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78
Q

Autosomal dominant disorders in the nervous system include? 4

A
  1. neurofibromatosis (von Recklinghausen)
  2. Huntington’s diseas
  3. myotonic dystrophy
  4. tuberous sclerosis (bourneville’s disease)
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79
Q

AD disorders in urinary system?

A

Adult polycystic kidney disease

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80
Q

Gastrointestinal AD disorder?

A

Familial polyposis coli

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81
Q

Hematopoietic AD disorder? 2

A
  1. hereditary spherocytosis

2. von willebrand disease

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82
Q

Neurofibromatosis Type 1 is known as what?

A

von Recklinghausen disease

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83
Q

What percentage of NF-1’s are spontaneous mutations?

A

50%

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84
Q

Which is more common, Type 1 or Type 2 NF?

A

Type 1 NF

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85
Q

What is the cause of NF-1

A

Defect of NF-1 gene on chromosome 17q11

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86
Q

NF-1 is what type of gene?

What does it produce?

A

Tumor suppressor gene

Neurofibromin

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87
Q

Clinical features of NF-1? 3

A
  1. Neurofibromas
  2. Cafe au lait macules
  3. Lisch nodules
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88
Q

What are the 4 types of neurofibromas in NF-1? Which is the one to watch for?

A
  1. cutaneous
  2. subcutaneous
  3. deep tissue
  4. plexiform: (WATCH THIS ONE)
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89
Q

Malignant tumors show up in NF-1 what percentage of the time?
What other things can NF-1 produce? (4)

A

3%

Skeletal abnormalities
Solid malignancies
CML
Reduced intelligence

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90
Q

What are lisch nodules?

A

Brown irregular discolorations in the iris

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91
Q

NF-2 has what clinical features? (5)

A
  1. Bilateral acoustic neuromas
  2. Multiple meningiomas
  3. Neurofibromas
  4. Cafe au lait macules
  5. NO Lisch nodules
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92
Q

NF-2 gene is found where?

What does it produce?

A

Ch 22

Merlin

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93
Q

Hereditary spherocytosis is developed how?

A

auto-hemolytic anemia characterized by the production of red blood cells that are sphere-shaped rather than bi-concave disk shaped (donut-shaped), and therefore more prone to hemolysis

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94
Q

AD skeletal disorders include what? 4

A
  1. marfan
  2. ehlers-danlos
  3. osteogenesis imperfecta
  4. Achondroplasia
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95
Q

Metabolic AD disorders? (2)

A
  1. familial hypercholesterolemia

2. acute intermittent porphyria

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96
Q

Marfan syndrome is due to what defective protein?
Where is this gene found?
Function of this protein normally?

A

Fibrillin
Ch 15
Provide stability to elastic tissue

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97
Q

Overall, Marfan is a disorder of what?

A

CT

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98
Q

What do you see in marfan syndrome? 7

A
  1. aortic dilatation leading to valve incompetence
  2. cystic medial necrosis leading to aortic dissection
  3. Mitral valve prolapse
  4. Increased stature
  5. Arachnodactyly
  6. Dislocated lens (ectopia lentis)
  7. Premare aging due to mucopolysaccharide deposition
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99
Q

Ehlers-danlos syndrome involves how many diseases?

A

12 variants

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100
Q

Ehler-danlos syndrome exhibits what type of inheritance?

A

All three

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101
Q

What collagen pathways are mutated in Ehlers-Danlos? 3

A

Type IV
Type VI
Type VII

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102
Q

How does ehler danlos present?

A
  1. Very stretchable skin
  2. hypermobile joints
    hypotonia at birth
  3. epicanthal folds and blue sclerae in eyes
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103
Q

What people do you see with Ehlers-Danlos?

A

Contortionists

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104
Q

Which is the most common mendelian disorder?

A

Familial hypercholesterolemia

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105
Q

What is the main cause of familial hypercholesterolemia?

A

Defective LDL receptor which regulates cholesterol metabolism

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106
Q

Clinical manifestations of familial Hypercholesterolemia?

A

High levels of total and LDL cholesterol

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107
Q

What are the five mutations that can result in hypercholesterolemia?

A

Class I: Can’t synthesize LDL receptor
Class II: Can’t transport LDL receptor to membrane
Class III: Can’t put LDL receptor into plasma membrane
Class IV: Can’t get LDL receptors to cluster in coated pit
Class V: Can’t recycle LDL receptors after use

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108
Q

Xanthomas are representative of what?

A

Hypercholesterolemia familial

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109
Q

Xanthelasma are representative of what?

A

Somewhat with hypercholesterolemia familial

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110
Q

Cystic fibrosis is what type of disorder?

A

Autosomal recessive systemic disorder of exocrine glands that affects mucus-secreting and eccrine glands

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111
Q

The defects in CF involve what abnormality?

What does this result in?

A

Electrolyte abnormalities

Abnormally thick mucus that can cause obstruction of excretory ducts which is really harmful in lungs and pancreas

112
Q

What reputation does CF have?

A

Most common fatal autosomal recessive disease affecting the Caucasian population

113
Q

Why does CF occur?

A

Defect in c-AMP-regulated ion transport across apical membranes of affected epithelial cells

114
Q

How does CF affect the sweat glands?

What does this mean clinically?

A

Failure of resorption of chloride in duct epithelial cells which results in high chloride levels in sweat.

the pilocarpine sweat test in which a value of sweat chloride above 60 mEq/L (normal being 10 mEq/L), along with symptoms consistent with CF, is essentially diagnostic

115
Q

How does CF affect the lungs and pancreatic duct cells?

A

Failure to transport chloride into lumen of airways and ducts which is coupled with increase sodium resorption which results in very thick viscid secretions that begin to obstruct. In the lungs this provides great environment for pseudomonas

116
Q

The CF gene has been localized to where?

What is the gene product?

A

Chromsome 7 long arm

CF transmembrane conductance regulator (CFTR) which is a chloride channel that can’t be activated by cAMP

117
Q

Heterozygous CF patients will display what?

A

Resistance to diarrheal diseases like cholera

118
Q

How many CF mutations exist?

Which is the most common at 70%?

A

300

Deletion of a 3 base pair encoding phenylalanine (Delta F508)

119
Q

How does CF affect the pancreas early on? 2
What follows? 3
What happens later?

A
  1. Cystic dilatation
  2. Direct plugging of exocrine glands and ducts with eosinophilic secretions

Acinar atrophy with rupture
Inflammation
Progressive fibrosis

Fatty and fibrous replacement of exocrine pancreas that spares islet cells usually

120
Q

How does CS begin in lungs? (2)
What follows?
What does long term CF give rise to? (3)

A
  1. Plugging of submucosal tracheal mucous glands and ducts
  2. Bronchioles become distended with mucus

Atelectasis
Emphysema

Chronic bronchitis
Bronchiectasis
Lung abscesses

121
Q

How does cystic fibrosis begin in liver?

What is seen resulting from this

A

Bile duct hyperplasia due to mucus plugging bile canaliculi

Focal biliary cirrhosis and diffuse hepatic nodularity

122
Q

CF in salivary glands show what?

A

Glandular dilatation and atrophy

123
Q

CF in the reproductive glands show what?

A

Obstruction of Wolffian duct derivatives like epididymis and vas deferens leads to azoospermia and infertility in 95% of males

124
Q

15% of infants with CF present with what?

What happens in this?

A

Meconium ileus

Obstruction of terminal ileus with risk of perforation and peritonitis

125
Q

CF is discovered when?

Because of what?

A

between 12 months and 2 years

Malabsorption symptoms due to pancreatic insufficiency

126
Q

What causes 80 to 90% of deaths in CF? 2

A

Obstructive pulmonary disease

Persistent pulmonary infections

127
Q

What is current therapy for CF? 3
How long can CF patients live now?
What is in the works for CF therapy?

A
  1. Pancreatic enzymes
  2. Fat soluble vitamins
  3. Antibiotics for pulmonary infections

50% live past 31

Normal DNA injected into respiratory epithelial cells

128
Q

Sickle cell anemia results from what type of mutation?

A

Missense

129
Q

Inheritance of a single mutant sickle cell alelle results in what?

A

Sickle cell Trait

130
Q

Sickle cell trait gives the person what?

A

Protection to malaria

131
Q

Sickle cell disease forms can also include what? (2)

A
  1. Sickle-hemoglobin C disease

2. Sickle-beta thalassemia

132
Q

How many genes make up hemoglobin?

Which chromosomes

A

4 alpha genes (2 HBA1 and 2 HBA2): Ch 16

2 beta genes: Ch 11

133
Q

Hemoglobin A has what chains?

What percentage of adult Hb is this form?

A

2 alpha and 2 beta

95%

134
Q

Hemoglobin A2 has what chains?

What percentage of adult Hb is this form?

A

Two alpha

Two delta

135
Q

Hemoglobin F has what chains?

A

Two alpha

Two gamma

136
Q

Hemoglobin S has what chains?

A

Two alpha

Two mutated Beta

137
Q

Hemoglobin AS has what chains?

A

Two alpha
One beta
One mutated Beta

138
Q

What hemoglobin genotypes are in sickle cell trait?

A

60% HbA

40% HbS

139
Q

Hemoglobin C has what chains?

A

Two alpha

Two mutated beta

140
Q

Hemoglobin SC has what chains?

A

Two alpha
1 Beta S mutation
1 Beta C mutation

141
Q

Hemoglobin E has what chains?

A

Two alpha

Two mutated beta (E mutation)

142
Q

How do sickle cells affect the blood?

A
  1. Increased adhesion causes infarcts in the kidney

2. Increased hemolysis in spleen that can result in autosplenectomy

143
Q

Phentylketonuria is what type of inheritance?

A

PKU

144
Q

PKU affects what people?

A

Scandinavian descent

145
Q

PKU is due to a severe lack of what enzyme?

A

Phenylalanine hydroxylase causing hyperphenylalaninemia and PKU

146
Q

No phenylalanine hydroxylase means what?

A

Can’t convert phenylalanine to tyrosine so metabolites form in urine and sweat

147
Q

How does PKU present at birth?

A

Doesn’t appear at birth, but within a few weeks have increasing plasma levels of phenylalanine and toxic metabolites

148
Q

Treatment of PKU is what?

A

Restrict ingestion of foods with phenyalanine during infancy and childhood

149
Q

PKU results in what within 6 months if it is not treated? 4

A

Mental retardation
Seizures
Eczema
Decreased pigementation

150
Q

PKU screening is performed when? What test?

A

Neonatal by the Guthrie test

151
Q

What is maternal PKU results from what? 2

A
  1. teratogenic effects of phenylalanine
  2. metabolites that cross the placenta in a female adults with PKU who don’t follow a phenylalanine restricted diet during pregnancy
152
Q

In PKU in adults, do the affected adults show symptoms?

Can they give up low Phenylalanine treatment?

A

Affected adults have no apparent adverse affects from elevated levels of phenylalanine and its metabolites after CNS development is complete

Yes, but NOT if pregnant

153
Q

Maternal PKU anomalies include? (6)

A 
Cardiac defects
Microcephaly
Low birth weight
Mental retardation
Slow development
Language deficits
154
Q

98% of PKU is due to a mutation in what?

A

PAH

155
Q

Galactosemia is what inheritance?

A

Autosomal recessive

156
Q

Galactosemia is the ability to do what?

A

Convert galactose to glucose because do not have galactose-1-phosphate urydil transferase

157
Q

Clinical presentation of galactosemia? (6)

A
  1. hepatomegaly and jaundice
  2. Cataracts
  3. Non-specific CNS changes
  4. failure to thrive
  5. vomiting
  6. diarrhea
158
Q

How can galactosemia be prevented?

A

No galactose in diet until age 2

159
Q

Lysosomal storage disease results from what?

A

Lack of lysosomal enzymes essential for normal function of lysosomes results in lysosomes storing non-metabolized products

160
Q

Example of glycogenoses?

A

Pompe

161
Q

Example of sphingolipidoses?

A

Tay-Sachs

162
Q

Example of sulfatidoses?

A

Gaucher

163
Q

Example of mucopolysaccharidoses?

A

Hurler

164
Q

Tay sachs results from what enzyme complex being mutated?

What does this cause?

A

Deficiency of Hexosaminidase A alpha subunit

GM2-ganglioside accumulation

165
Q

The GM2-ganglioside accumulation of TaySachs is where?

Main manifestation?

A

Neurons of CNS and ANS

Retinal cherry red spot

166
Q

Tay-Sachs disease is most common with what population?

When do they die?

A

Ashkenazi Jews

Death by 2-3 years

167
Q

What does Niemann Pick disease result from?

A

Accumulation of sphingomyelin and cholesterol

168
Q

What types of Niemann-Pick are there?
Which is most common?
Which is most common in Ashkenazi?

A

A, B, C
C most common
A and B

169
Q

Type A of Niemann Pick is known as what form?

What symptoms? (4)

A

Severe infantile form

Neuronal death with resultant brain shrinkage
Retinal cherry spot
Hepatosplenomegaly and lymphadenopathy
Death at age 1-3

170
Q

Type C Niemann Pick has what gene affected?

What does this gene control?

A

NPC-1

Cholesterol trafficking

171
Q

Heterogeneous Niemann Pick Type C shows what? 3

A

Hydrops fetalis and still birth
Neonatal hepatitis
Chronic form with progressive neurologic damage

172
Q

Gaucher disease is characterized by mutation in what gene?

What does this lead to?

A

Glucocerebrosidase gene

Decreased levels or activity of this enzyme

173
Q

Three subtypes of Gaucher disease?

A

Type I
Type II
Type III

174
Q

Type I gaucher disease is involved with what cells?

A

Mononuclear phagocytes, NOT the CNS.

175
Q

What changes are common in Type I gaucher?

Which population has it the most

A

Spleen and skeletal

Eastern European Jews

176
Q

What is Type II and Type III Gaucher’s disease known as?

A

Type II: Infantile acute cerebral form

Type III: Intermediate form

177
Q

All forms of Gaucher have elevated levels of what enzyme?

A

Chitotriosidase

178
Q

Type I Gaucher has what appearance under microscopy?

A

Crumpled tissue paper

179
Q

Hunter and Hurler syndromes are examples of what?

A

Mucopolysaccharidoses

180
Q

All mucopolysaccharidoses have what inheritance?

The one exception?

A

Autosomal recessive

Hunter: X-linked recessive

181
Q

Common features of mucopolysaccharidoses? 4

A

Coarse facial features
Clouding of the corneas
Joint stiffness
Mental retardation

182
Q

What is glycogenoses the result of?

A

metabolic defect in the synthesis or catabolism of glycogen

183
Q

What are the three main types of Glycogenoses?

A 
Hepatic type (von Gierke disease, type I)
Myopathic type (McArdle syndrome, type V)
Miscellaneous types (Pompe disease, type II)
184
Q

Pompe is due to what deficiency?

A

lysosomal Acid maltase

185
Q

Hepatic glycogen storage disease will cause what?

A

Feeling hungry and not nourished

186
Q

Myopathic glycogen storage disease will cause what?

A

Muscle weakness

187
Q

McArdle is due to what deficiency?

A

Phosphorylase

188
Q

von Gierke’s disease is due to what deficiency?

A

Glucose-6-phosphatase

189
Q

Pompe has characteristics of what two sets of disorders?

A
  1. glycogen storage

2. lysosomal storage

190
Q

In pompe, what happens to the glycogen?

A

Accumulates in organs, especially the heart, and causes death

191
Q

What is the heredity of alkatonuria?

A

Autosomal recessive

192
Q

Alkaptonuria is caused by what?

A

lack of homogentisic oxidase causing build-up of homogentisic acid

193
Q

In alkaptonuria, where does the homogentisic build up go?

A
  1. Excreted in urine which will stain black upon staining

2. Ochronosis

194
Q

What is ochronosis?

where is this seen the most?

A

homogentisic acid binds to collagen in tissues imparting black-blue pigmentation to these tissues

ears, nose, cheeks, joints

195
Q

Fragile X is different from the other x linked recessive diseases how?

A

It’s seen as X-linked recessive and x-linked dominant. It’s a triple nucleotide repeat that doesn’t play by the rules.

196
Q

What are all the possible disorders located on X chromosome

A 
Duchenne Muscular Dystrophy
Becker Muscular Dystrophy
Hemophilia A & B
Glucose-6-phosphate dehydrogenase deficiency
Chronic granulomatous disease
Lesch-Nyhan syndrome
Diabetes insipidus
Fragile X syndrome
Ocular albinism
Chronic granulomatous disease
Menkes syndrome
Testicular feminization
X-linked SCID
X-linked agammaglobinulinemia
Fabry disease
Hunter Syndrome
197
Q

Multifactorial inheritance results from what?

A

combined actions of environmental influences and the additive effects of two or more mutant genes

198
Q

Risk of a multifactorial inheritance increases with what?

A

increases with the number of abnormal genes inherited

199
Q

Normal phenotypic multifactoral characteristics include? 4

A
  1. hair color
  2. height
  3. eye
  4. skin color
200
Q

in multifactorial inheritance, is the rate of recurrence the same for all the siblings?

A

YES 2-7%

201
Q

Disorders/defects associated with multifactoral inheritance include? 7

A

cleft lip/palate, congenital heart disease, coronary heart disease, hypertension, gout, diabetes mellitus and pyloric stenosis

202
Q

What is a karyotype?

A

An arrangement of chromosomes that is obtained from freshly obtained dividing cells such as leukocytes, fibroblasts, or amniocytes

203
Q

Cytogenetic notation of normal female?

A

46,XX

204
Q

Cytogenetic notation of female with down’s?

A

47,XX +21

205
Q

Cytogenetic notation of female with Turner’s?

A

45,X

206
Q

What does the notation mean (45,XX der(13,14)?

A

Designates a “derived” (der) chromosome formed from the fusion of the long arms of chromosomes 13 and 14 with loss of the short arm material from both chromosomes

207
Q

A derived chromosome can only occur with what chromosomes?

A

The five acrocentric (minimal short arms) chromosomes: 13, 14, 15, 21, 22

208
Q

What does 46,XX,del (5p) mean?

A

deletion of DNA from the short arm of chromosome

209
Q

What does 46,XY t(9;22)(q34;q11) mean?

A

reciprocal translocation between chromosomes 9 and 22. This forms the abnormal BCR-ABL gene seen in chronic myelogenous leukemia. Also known as the Philadelphia chromosome

210
Q

What does 46,XY inv(16), t(16;16) mean?

A

Designates an inversion translocation in which a segment of chromosome 16 DNA is reversed or inverted within the chromosome

211
Q

A paracentric inversion involves the centromere, yes or no?

A

No

212
Q

A pericentric inversion involves the centromere, yes or no?

A

Yes

213
Q

Karyotyping involves looking at chromosomes when?
How is this accomplished?
What stain is used?

A

metaphase portion of mitosis

mitosis—use the drug colchicine to stop the mitotic cycle in metaphase

Giemsa

214
Q

Can chromosomes be distinguished from each other in karyotyping? How?

A

Yes

They have different banding patterns

215
Q

What does q mean?

A

Long arm

216
Q

What does p mean?

A

Short arm

217
Q

Cytogenetic disorders are defined how?

A

Disorders that involve abnormal numbers or structures of chromosomes per classic karyotyping

218
Q

What is diploid for humans?

A

46XX or 46XY (2N)

219
Q

What is triploid for humans?

A

69XXX, etc, (3N)

220
Q

What is aneuploid for humans?

A

Not Diploid or Polyploid (3N, 4N, etc.)

221
Q

What is monosomy

What is trisomy?

A

Loss of chromosome

Gain of chromosome

222
Q

FISH studies can be used to identify what?
Do you need dividing cells?
What must you know before starting?

A

specific DNA sequence in interphase nuclei as well as in karyotyping studies

no

specific DNA sequences to design the probes, which are labeled with a fluorescing compound

223
Q

What is mosaicism?

A

presence of two or more populations of cells with different genotypes in a single individual

224
Q

Examples of mosaicism? 3

A
  1. normal cells and monosomy
  2. normal cells and trisomy
  3. normal cells with specific gene mutation
225
Q

Monosomy and trisomy usually result from what?

A

nondisjunction of chromosomes during gametogenesis (meiosis)

226
Q

Mosaicism results from what

A

errors in mitosis in the zygote

227
Q

What are the 3 main trisomies?

How common is each

A

21: Downs (most common)
18: Edwards
13: Patau (least common)

228
Q

What is Edwards karyotype?

A

47, XY, +18

229
Q

What are some common Edwards symptoms? 6

A 
kidney malformations, 
structural heart defects at birth
omphalocele
esophageal atresia
mental retardation
developmental delays
230
Q

What is Patau karyotype?

A

47, XY, +13

231
Q

What are some common Patau symptoms?

A

Mental retardation and motor disorder
Microcephaly
Polydactyly (extra digits)

232
Q

What is the MOST common of the chromsomal disorders?

A

Trisomy 21

233
Q

Down syndrome risk for child increases with what?

A

Increased maternal age

234
Q

Most common cause of trisomy 21 is what?

A

meiotic nondisjunction; 47,XX or XY, +21 (95%)

235
Q

Three causes of trisomy 21? 3

A
  1. Meiotic nondisjunction
  2. Robertsonian translocation
  3. Mosaics
236
Q

Clinical findings of down’s include? 8

A
  1. Flat facial profile
  2. Oblique palpebral fissures
  3. Epicanthic folds
  4. Congenital heart disease (40%), especially endocardial cushion defects
  5. Acute leukemia (10-20X increased risk)
  6. GI atresia,
  7. Alzheimer disease (in patients older than 40),
  8. immunodeficiencies
237
Q

what is the Lyon hypothesis of cytogenetic disorders invovling sex chromosomes?

A

Only one active X chromosome is needed and the other copy(ies) are inactivated and become Barr bodies.

238
Q

Can you have mosaics with sex chromosome disorders?

A

yes, if different X chromosomes are inactivated in different tissues. Some maternal cells may have both X chromosomes active

239
Q

How do placental mammals and marsupial mammals differ in terms of X chromosome disorders?

A

In placental mammals either X chromosome may be inactivated, but in marsupial mammals the paternal X chromosome is preferentially inactivated

240
Q

Normaly, sex chromosome disorders cause what?

A

subtle, chronic problems relating to sexual development and fertility

241
Q

The higher the number of X chromosomes, the greater the likelihood of what?

A

Mental retardation

242
Q

What is Klinefelter’s syndrome?

A

Male hypogonadism that occurs when there are two or more X chromosomes and at least one Y chromosome (needed for the male phenotype

243
Q

What is the classic form of Klinefelter’s?

A

47,XXY

244
Q

What are some mosaic examples of Klinefelter’s?

A

46,XY/47,XXY

49,XXXXY

245
Q

Manifestations of klinefelter’s? 10

A
  1. Slightly low IQ,
  2. increased risk of mental retardation with additional copies of the X chromosome
  3. Atrophic testes,
  4. hypospadias,
  5. cryptorchidism,
  6. infertility,
  7. gynecomastia,
  8. female distribution of fat and skeletal abnormalities
  9. Increased breast cancer
  10. autoimmune disorders
246
Q

Full chromsomal monosomy of any sort will resort in what?

A

Spontaneous abortion

247
Q

Trisomy X entails what?

A

Syndrome in which females have an extra X chromosome - 47 XXX - two Barr bodies in cells

248
Q

Trisomy X patients are at risk for what? (3)

A

Developmental delays
Speech, language and learning disabilities
Tall stature and poor muscle tone

249
Q

Most trisomy X patients have what symptoms?

A

Just mild effects and will never be diagnosed

250
Q

XYY Males have what karyotype?

A

47,XYY or 48,XYYY

251
Q

XYY males have what symptoms? (3)

A
  1. tall
  2. acne
  3. antisocial behavior
252
Q

Turner syndrome results from what?

A

complete or partial monosomy of the X chromosome

253
Q

Turner syndrome is characterized primarily by what?

A

hypogonadism in phenotypic females

254
Q

Turner syndrome clinical findings? (8)

A 
Short stature
Coarctation of aorta
Edema
Cystic hygromas
Webbing of the neck
Broad (shield) chest with widely spaced nipples
Streak ovaries
Nevi
255
Q

Main symptoms of Turner syndrome? (4)

A

Primary amenorrhea
Infantile genitalia
Hypothyroidism
Insulin resistance

256
Q

Nonmedelian inheritance includes what types of disorders? 4

A
  1. Triplet repeat
  2. genomic imprinting
  3. mitochondrial mutations
  4. gonadal mosaicism
257
Q

Triplet repeat mutations are caused by what?

A

Caused by long segments of repeating nucleotides

258
Q

Genomic imprinting involves what?

A

preferential down regulation (turning off) of genes

259
Q

What are premutations?

A

increased numbers of trinucleotide repeats, but not enough to meet characteristics of full mutation

260
Q

What is a full mutation?

A

Additional triple repeats with full spectrum of phenotypic changes

261
Q

What is anticipation?

A

Clinical features worsen with each successive generation as a result of amplification of trinucleotide repeats during oogenesis or spermatogenesis

262
Q

What is Sherman’s Paradox?

A

Risk of having the full mutation and increased phenotypic changes depends on the position of the individual in the pedigree

263
Q

Triplet repeat mutations include? (4)

A

Fragile X syndrome
Myotonic dystrophy
Friedreich ataxia
Huntington disease

264
Q

What makes Huntington’s disease special from other triplet repeat disorders?

A

Gain of function mutation

265
Q

CGG triplet in an UTR is what mutation?

A

Fragile X

266
Q

GAA triplet in an intron is what mutation?

A

Friedreich ataxia

267
Q

CAG triplet in an extron is what mutation?

A

Huntington’s disease

268
Q

Fragile X syndrome involves what gene?

A

FMR-1

269
Q

Why is the disease called Fragile X syndrome?

A

the triple repeats give the X chromosome a “broken” appearance on G banding

270
Q

How does Fragile X rate in terms of mental retardation diseases?

A

Second behind Downs

271
Q

Characteristic phenotype of Fragile X? (3)

A
  1. Long face with large mandible,
  2. large, everted ears,
  3. macroorchidism in 90% of post-pubertal males
272
Q

What phenotype of a disease is similar to Fragile X’s?

A

Marfan

273
Q

Fragile site is seen where on the chromosome?

A

Xq27.3

274
Q

At the fragile site, what is found?

A

CGG is the trinucleotide repeat

275
Q

Normal CGC repeat at the fragile site?

A

29 or less

276
Q

Premutation CGC repeat at fragile site?

A

50-200

277
Q

Full mutation CGC repeat at fragile site?

A

250-4000

Pathology (36 decks)

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