Ch9: Genetics Flashcards Preview

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Flashcards in Ch9: Genetics Deck (277):
1

Disorders related to single gene usually follow what inheritance pattern?

Mendelian

2

Two types of single gene mutations?

1. Mendelian
2. Non-classic inheritance

3

What is a mutation?

Permanent change in DNA of an organism

4

What is a genome mutation?

Loss or gain of whole chromosomes

5

What is a chromosomal mutation?

Structural changes to chromosomes

6

What are gene mutations?

Change at gene level

7

What are the two categories of gene mutations?

1. Point mutations
2. Frameshift mutation

8

What are the two types of point mutations?

1. Nonsense mutation
2. Missense mutation

9

What are the two types of frameshift mutations?

1. Insertions
2. Deletions

10

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

Both

11

What is the longest chromosome?

Chromosome 1

12

Which is the shortest chromosome?

Chromosome 22

13

What is a balanced reciprocal translocation?

exchange of material between nonhomologous chromosomes

14

What is a Robertsonian translocation?

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

15

What is an isochromosome?

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

16

What is a paracentric inversion?

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

17

What is a pericentric inversion?

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

18

How does a ring chromosome form?

chromosome whose arms have fused together to form a ring

19

Hemoglobin S is the result of what type of mutation?

Point mutation causing a missense mutation

20

What is the exact change in hemoglobin S?

GAG becomes GUG which encodes valine instead of glutamic acid

21

What type of mutation is beta thalassemia?

Point mutation causing a nonsense mutation.

22

What type of mutation is the ABO O allele?

Frameshift mutation from a single base deletion

23

Hexosaminidase A/Tay Sachs is the result of what?

Frameshift mutation caused by four base insertion

24

Cystic fibrosis is the result of what?

Three base deletion that does NOT cause a frameshift

25

Fragile X syndrome is the result of what?

CGG triplet repeat

26

Friederich ataxia is the result of what?

GAA triplet repeat

27

Huntington's disease is the result of what?

CAG triplet repeat

28

Myotonic dystrophy is the result of what?

CTG repeat

29

What is myoclonus epilepsy the result of what?

12 repeat: CCCCGCCCCGCG

30

What is a mendelian disorder?

Genetic disorder of large effect caused by a single gene mutation

31

What is the one common X-linked dominant disorder?

Vitamin D resistant rickets

32

3 mendelian disorder types

1. Autosomal dominant
2. Autosomal recessive
3. X-linked recessive

33

Autosomal dominant is a disorder manifested in what genotype?

heterozygous

34

When do autosomal dominant disorders present?

Onset delay until adulthood

35

Can autosomal dominant disorders spontaneously occur in the germline?

yes

36

What modifies the expression of autosomal dominant genotype?

1. Reduced penetrance
2. variable expressivity

37

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

Control points in metabolic pathways
Key structural proteins

38

Autosomal recessive disorders are manifested only in what genotype?

Homozygous state

39

Siblings in AR disease have what chance of being affected?
Of being carriers?

1 in 4 chance of being affected

1 in 2 chance of being a carrier

40

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

Population is consanguineous

41

Which has more uniform expression, autosomal dominant or recessive?

Recessive

42

Is complete penetrance common in AR?

Yes

43

When does onset of autosomal recessive occur?

Early in life

44

Can spontaneous mutations occur of autosomal recessive genes?

Yes, but takes awhile to present (several generations)

45

Autosomal recessive genes usually encode for what?

Enzyme

46

What protects us against a heterozygous autosomal recessive genotype?

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

47

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

2

48

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

1

49

Who transfers the X-linked recessive gene?

Heterozygous female

50

Who receives the X-linked recessive gene?

Sons (1 in 2 chance)

51

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

Lyonization

52

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

All daughters will be carriers

53

What is codominance?

When two different gene alleles are fully expressed together.

54

What are examples of codominance? (2)

1. Histocompatibility
2. Blood groups

55

Codominant Mendelian disorders occur when?

When both normal and mutant gene are fully expressed

56

What are examples of some codominance disorders? (2)

1. Thalassemias
2. Sickle cell anemia

57

What is penetrance?

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

58

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

Complete penetrance

59

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

Reduced penetrance

60

What is variable expressivity?

Degree of phenotypic change seen in affected individuals.

61

Example of variable expressivity?

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

62

What is polymorphism?

Existence of more than one normal allele of a gene.

63

What are examples of polymorphisms? 2

1. histocompatibility genes
2. Blood group genes

64

What are the most common form of polymorphisms?

SNP's

65

SNP's occur in coding regions how often?

1%

66

What is pleiotropism?

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

67

What are two examples of pleiotropism?

1. Marfan syndrome
2. Neurofibromatosis

68

What is genetic heterogeneity?

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

69

Example of genetic heterogeneity? (2)

1. Retinitis pigmentosa
2. Childhood deafness

70

What is the phenotype?

Physical appearance or biochemical characteristics as distinguished from its genotype

71

What is genotype?

genetic makeup of an organism as distinguished from its physical characteristics

72

Two types of non-protein producing genes?

1. miRNA
2. lcRNA

73

What are miRNA?

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

74

The RNA-induced silencing complex interacts with what?
To what effect?

miRNA
Cleave or suppress translation of mRNA

75

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

Spontaneous mutation

76

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

Loss

77

Two main characterizations of AD disorders?

1. variable expressivity
2. reduced penetrance

78

Autosomal dominant disorders in the nervous system include? 4

1. neurofibromatosis (von Recklinghausen)
2. Huntington's diseas
3. myotonic dystrophy
4. tuberous sclerosis (bourneville's disease)

79

AD disorders in urinary system?

Adult polycystic kidney disease

80

Gastrointestinal AD disorder?

Familial polyposis coli

81

Hematopoietic AD disorder? 2

1. hereditary spherocytosis
2. von willebrand disease

82

Neurofibromatosis Type 1 is known as what?

von Recklinghausen disease

83

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

50%

84

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

Type 1 NF

85

What is the cause of NF-1

Defect of NF-1 gene on chromosome 17q11

86

NF-1 is what type of gene?
What does it produce?

Tumor suppressor gene
Neurofibromin

87

Clinical features of NF-1? 3

1. Neurofibromas
2. Cafe au lait macules
3. Lisch nodules

88

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

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

89

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

3%

Skeletal abnormalities
Solid malignancies
CML
Reduced intelligence

90

What are lisch nodules?

Brown irregular discolorations in the iris

91

NF-2 has what clinical features? (5)

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

92

NF-2 gene is found where?
What does it produce?

Ch 22
Merlin

93

Hereditary spherocytosis is developed how?

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

94

AD skeletal disorders include what? 4

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

95

Metabolic AD disorders? (2)

1. familial hypercholesterolemia
2. acute intermittent porphyria

96

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

Fibrillin
Ch 15
Provide stability to elastic tissue

97

Overall, Marfan is a disorder of what?

CT

98

What do you see in marfan syndrome? 7

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

99

Ehlers-danlos syndrome involves how many diseases?

12 variants

100

Ehler-danlos syndrome exhibits what type of inheritance?

All three

101

What collagen pathways are mutated in Ehlers-Danlos? 3

Type IV
Type VI
Type VII

102

How does ehler danlos present?

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

103

What people do you see with Ehlers-Danlos?

Contortionists

104

Which is the most common mendelian disorder?

Familial hypercholesterolemia

105

What is the main cause of familial hypercholesterolemia?

Defective LDL receptor which regulates cholesterol metabolism

106

Clinical manifestations of familial Hypercholesterolemia?

High levels of total and LDL cholesterol

107

What are the five mutations that can result in hypercholesterolemia?

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

108

Xanthomas are representative of what?

Hypercholesterolemia familial

109

Xanthelasma are representative of what?

Somewhat with hypercholesterolemia familial

110

Cystic fibrosis is what type of disorder?

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

111

The defects in CF involve what abnormality?
What does this result in?

Electrolyte abnormalities

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

112

What reputation does CF have?

Most common fatal autosomal recessive disease affecting the Caucasian population

113

Why does CF occur?

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

114

How does CF affect the sweat glands?
What does this mean clinically?

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

How does CF affect the lungs and pancreatic duct cells?

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

The CF gene has been localized to where?
What is the gene product?

Chromsome 7 long arm
CF transmembrane conductance regulator (CFTR) which is a chloride channel that can't be activated by cAMP

117

Heterozygous CF patients will display what?

Resistance to diarrheal diseases like cholera

118

How many CF mutations exist?
Which is the most common at 70%?

300
Deletion of a 3 base pair encoding phenylalanine (Delta F508)

119

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

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

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

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

Atelectasis
Emphysema

Chronic bronchitis
Bronchiectasis
Lung abscesses

121

How does cystic fibrosis begin in liver?
What is seen resulting from this

Bile duct hyperplasia due to mucus plugging bile canaliculi

Focal biliary cirrhosis and diffuse hepatic nodularity

122

CF in salivary glands show what?

Glandular dilatation and atrophy

123

CF in the reproductive glands show what?

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

124

15% of infants with CF present with what?
What happens in this?

Meconium ileus

Obstruction of terminal ileus with risk of perforation and peritonitis

125

CF is discovered when?
Because of what?

between 12 months and 2 years

Malabsorption symptoms due to pancreatic insufficiency

126

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

Obstructive pulmonary disease
Persistent pulmonary infections

127

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

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

50% live past 31

Normal DNA injected into respiratory epithelial cells

128

Sickle cell anemia results from what type of mutation?

Missense

129

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

Sickle cell Trait

130

Sickle cell trait gives the person what?

Protection to malaria

131

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

1. Sickle-hemoglobin C disease
2. Sickle-beta thalassemia

132

How many genes make up hemoglobin?
Which chromosomes

4 alpha genes (2 HBA1 and 2 HBA2): Ch 16
2 beta genes: Ch 11

133

Hemoglobin A has what chains?
What percentage of adult Hb is this form?

2 alpha and 2 beta

95%

134

Hemoglobin A2 has what chains?
What percentage of adult Hb is this form?

Two alpha
Two delta

135

Hemoglobin F has what chains?

Two alpha
Two gamma

136

Hemoglobin S has what chains?

Two alpha
Two mutated Beta

137

Hemoglobin AS has what chains?

Two alpha
One beta
One mutated Beta

138

What hemoglobin genotypes are in sickle cell trait?

60% HbA
40% HbS

139

Hemoglobin C has what chains?

Two alpha
Two mutated beta

140

Hemoglobin SC has what chains?

Two alpha
1 Beta S mutation
1 Beta C mutation

141

Hemoglobin E has what chains?

Two alpha
Two mutated beta (E mutation)

142

How do sickle cells affect the blood?

1. Increased adhesion causes infarcts in the kidney
2. Increased hemolysis in spleen that can result in autosplenectomy

143

Phentylketonuria is what type of inheritance?

PKU

144

PKU affects what people?

Scandinavian descent

145

PKU is due to a severe lack of what enzyme?

Phenylalanine hydroxylase causing hyperphenylalaninemia and PKU

146

No phenylalanine hydroxylase means what?

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

147

How does PKU present at birth?

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

148

Treatment of PKU is what?

Restrict ingestion of foods with phenyalanine during infancy and childhood

149

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

Mental retardation
Seizures
Eczema
Decreased pigementation

150

PKU screening is performed when? What test?

Neonatal by the Guthrie test

151

What is maternal PKU results from what? 2

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

In PKU in adults, do the affected adults show symptoms?
Can they give up low Phenylalanine treatment?

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

Maternal PKU anomalies include? (6)

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

154

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

PAH

155

Galactosemia is what inheritance?

Autosomal recessive

156

Galactosemia is the ability to do what?

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

157

Clinical presentation of galactosemia? (6)

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

158

How can galactosemia be prevented?

No galactose in diet until age 2

159

Lysosomal storage disease results from what?

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

160

Example of glycogenoses?

Pompe

161

Example of sphingolipidoses?

Tay-Sachs

162

Example of sulfatidoses?

Gaucher

163

Example of mucopolysaccharidoses?

Hurler

164

Tay sachs results from what enzyme complex being mutated?
What does this cause?

Deficiency of Hexosaminidase A alpha subunit
GM2-ganglioside accumulation

165

The GM2-ganglioside accumulation of TaySachs is where?
Main manifestation?

Neurons of CNS and ANS

Retinal cherry red spot

166

Tay-Sachs disease is most common with what population?
When do they die?

Ashkenazi Jews
Death by 2-3 years

167

What does Niemann Pick disease result from?

Accumulation of sphingomyelin and cholesterol

168

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

A, B, C
C most common
A and B

169

Type A of Niemann Pick is known as what form?
What symptoms? (4)

Severe infantile form

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

170

Type C Niemann Pick has what gene affected?
What does this gene control?

NPC-1
Cholesterol trafficking

171

Heterogeneous Niemann Pick Type C shows what? 3

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

172

Gaucher disease is characterized by mutation in what gene?
What does this lead to?

Glucocerebrosidase gene
Decreased levels or activity of this enzyme

173

Three subtypes of Gaucher disease?

Type I
Type II
Type III

174

Type I gaucher disease is involved with what cells?

Mononuclear phagocytes, NOT the CNS.

175

What changes are common in Type I gaucher?
Which population has it the most

Spleen and skeletal
Eastern European Jews

176

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

Type II: Infantile acute cerebral form
Type III: Intermediate form

177

All forms of Gaucher have elevated levels of what enzyme?

Chitotriosidase

178

Type I Gaucher has what appearance under microscopy?

Crumpled tissue paper

179

Hunter and Hurler syndromes are examples of what?

Mucopolysaccharidoses

180

All mucopolysaccharidoses have what inheritance?
The one exception?

Autosomal recessive
Hunter: X-linked recessive

181

Common features of mucopolysaccharidoses? 4

Coarse facial features
Clouding of the corneas
Joint stiffness
Mental retardation

182

What is glycogenoses the result of?

metabolic defect in the synthesis or catabolism of glycogen

183

What are the three main types of Glycogenoses?

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

184

Pompe is due to what deficiency?

lysosomal Acid maltase

185

Hepatic glycogen storage disease will cause what?

Feeling hungry and not nourished

186

Myopathic glycogen storage disease will cause what?

Muscle weakness

187

McArdle is due to what deficiency?

Phosphorylase

188

von Gierke's disease is due to what deficiency?

Glucose-6-phosphatase

189

Pompe has characteristics of what two sets of disorders?

1. glycogen storage
2. lysosomal storage

190

In pompe, what happens to the glycogen?

Accumulates in organs, especially the heart, and causes death

191

What is the heredity of alkatonuria?

Autosomal recessive

192

Alkaptonuria is caused by what?

lack of homogentisic oxidase causing build-up of homogentisic acid

193

In alkaptonuria, where does the homogentisic build up go?

1. Excreted in urine which will stain black upon staining
2. Ochronosis

194

What is ochronosis?
where is this seen the most?

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

ears, nose, cheeks, joints

195

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

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

What are all the possible disorders located on X chromosome

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

Multifactorial inheritance results from what?

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

198

Risk of a multifactorial inheritance increases with what?

increases with the number of abnormal genes inherited

199

Normal phenotypic multifactoral characteristics include? 4

1. hair color
2. height
3. eye
4. skin color

200

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

YES 2-7%

201

Disorders/defects associated with multifactoral inheritance include? 7

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

202

What is a karyotype?

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

203

Cytogenetic notation of normal female?

46,XX

204

Cytogenetic notation of female with down's?

47,XX +21

205

Cytogenetic notation of female with Turner's?

45,X

206

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

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

A derived chromosome can only occur with what chromosomes?

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

208

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

deletion of DNA from the short arm of chromosome

209

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

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

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

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

211

A paracentric inversion involves the centromere, yes or no?

No

212

A pericentric inversion involves the centromere, yes or no?

Yes

213

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

metaphase portion of mitosis

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

Giemsa

214

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

Yes
They have different banding patterns

215

What does q mean?

Long arm

216

What does p mean?

Short arm

217

Cytogenetic disorders are defined how?

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

218

What is diploid for humans?

46XX or 46XY (2N)

219

What is triploid for humans?

69XXX, etc, (3N)

220

What is aneuploid for humans?

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

221

What is monosomy
What is trisomy?

Loss of chromosome
Gain of chromosome

222

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

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

What is mosaicism?

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

224

Examples of mosaicism? 3

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

225

Monosomy and trisomy usually result from what?

nondisjunction of chromosomes during gametogenesis (meiosis)

226

Mosaicism results from what

errors in mitosis in the zygote

227

What are the 3 main trisomies?
How common is each

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

228

What is Edwards karyotype?

47, XY, +18

229

What are some common Edwards symptoms? 6

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

230

What is Patau karyotype?

47, XY, +13

231

What are some common Patau symptoms?

Mental retardation and motor disorder
Microcephaly
Polydactyly (extra digits)

232

What is the MOST common of the chromsomal disorders?

Trisomy 21

233

Down syndrome risk for child increases with what?

Increased maternal age

234

Most common cause of trisomy 21 is what?

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

235

Three causes of trisomy 21? 3

1. Meiotic nondisjunction
2. Robertsonian translocation
3. Mosaics

236

Clinical findings of down's include? 8

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

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

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

238

Can you have mosaics with sex chromosome disorders?

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

239

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

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

240

Normaly, sex chromosome disorders cause what?

subtle, chronic problems relating to sexual development and fertility

241

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

Mental retardation

242

What is Klinefelter's syndrome?

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

243

What is the classic form of Klinefelter's?

47,XXY

244

What are some mosaic examples of Klinefelter's?

46,XY/47,XXY
49,XXXXY

245

Manifestations of klinefelter's? 10

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

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Full chromsomal monosomy of any sort will resort in what?

Spontaneous abortion

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Trisomy X entails what?

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

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

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

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Most trisomy X patients have what symptoms?

Just mild effects and will never be diagnosed

250

XYY Males have what karyotype?

47,XYY or 48,XYYY

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XYY males have what symptoms? (3)

1. tall
2. acne
3. antisocial behavior

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Turner syndrome results from what?

complete or partial monosomy of the X chromosome

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Turner syndrome is characterized primarily by what?

hypogonadism in phenotypic females

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Turner syndrome clinical findings? (8)

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

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Main symptoms of Turner syndrome? (4)

Primary amenorrhea
Infantile genitalia
Hypothyroidism
Insulin resistance

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Nonmedelian inheritance includes what types of disorders? 4

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

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Triplet repeat mutations are caused by what?

Caused by long segments of repeating nucleotides

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Genomic imprinting involves what?

preferential down regulation (turning off) of genes

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What are premutations?

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

260

What is a full mutation?

Additional triple repeats with full spectrum of phenotypic changes

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What is anticipation?

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

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What is Sherman's Paradox?

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

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Triplet repeat mutations include? (4)

Fragile X syndrome
Myotonic dystrophy
Friedreich ataxia
Huntington disease

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

Gain of function mutation

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CGG triplet in an UTR is what mutation?

Fragile X

266

GAA triplet in an intron is what mutation?

Friedreich ataxia

267

CAG triplet in an extron is what mutation?

Huntington's disease

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Fragile X syndrome involves what gene?

FMR-1

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Why is the disease called Fragile X syndrome?

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

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

Second behind Downs

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Characteristic phenotype of Fragile X? (3)

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

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

Marfan

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Fragile site is seen where on the chromosome?

Xq27.3

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At the fragile site, what is found?

CGG is the trinucleotide repeat

275

Normal CGC repeat at the fragile site?

29 or less

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Premutation CGC repeat at fragile site?

50-200

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Full mutation CGC repeat at fragile site?

250-4000