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Human Bioscience II > Genetic Diseases > Flashcards

Genetic Diseases Flashcards

1
Q

How common are genetic diseases (%)?

Are pediatric diseases genetic in origin?

A

67%

Many pediatric diseases are not of genetic origin and they don’t all manifest in infancy and childhood

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2
Q

What’s the difference between hereditary disorders and congenital disorders?

A

Hereditary disorders are derived from one’s parents and transmitted in gametes through generations

Congenital disorders are present at birth

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3
Q

What are the types of genetic diseases found in genetic disorders?

A

Single Gene
Multifactorial (multigenic)
Chromosomal

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4
Q

What is single gene disease?

A

Abnormalities or mutations in the sequence of one gene; highly penetrant & follow classical Mendelian inheritance patterns

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5
Q

What is multifactorial (multigenic) disease?

A

Caused by the complex interaction of multiple variant (not mutant) forms of genes (polymorphisms) and environmental factors

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6
Q

What is chromosomal disease?

A

Abnormalities in chromosome structure (breaks) or numerical alternations (missing or extra copies) highly penetrant

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7
Q

What are mutations?
What are the common types of mutations?
Which types of tissues do mutations affect?

A

Permanent change in DNA

  1. Point mutation
  2. Frameshift mutations
  3. Trinucleotide repeat mutations

Occurs in both germline and somatic tissues

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8
Q

What is a trinucleotide repeat mutation?

A

Amplification of a sequence of three nucleotides that have Guanine (G) and Cytosine (C)
- Repeated trinucleotide adds a string of glutamines to the protein

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9
Q

What is a frameshift mutaiton?

A

Insertion or deletion of one or two base pairs alters the reading frame of the DNA strand

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10
Q

What are nonmutation alternations in protein coding genes?

A

Structural changes:
- Deletions
- Inversions
- Translocations

  • Epigenetic Changes: Hypermethylation, Acetylation
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11
Q

What are the alterations in noncoding RNAs?

A

miRNA- Affect oncogenes or tumor suppressor genes

siRNA

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12
Q

What types of transmission patterns do single gene disorders follow?

What type of inheritance pattern do single gene defects follow?

A

Autosomal dominant disorders
Autosomal recessive diseases
X-linked disorders

Defects follow Mendelian pattern of inheritance

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13
Q

What are characteristics of autosomal dominant disorders?

Which types of proteins are/ aren’t affected?

A

Expressed in heterozygous state
Affect male/females equally
Both sexes can transmit the disorder

Enzyme proteins are not affected in autosomal dominant disorders; receptor/ structural proteins are involved

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14
Q

What are characteristics of autosomal recessive disorders?

Which types of proteins are/ aren’t affected?

A

Occur when both copies of a gene are mutated
Affects male and females equally

Enzyme proteins are involved

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15
Q

What are characteristics of X-linked disorders?

Who is protected and how?

A

Transmitted by heterozygous females to their sons, who manifest the disease

Female carriers are protected because of random inactivation of one X chromosome

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16
Q

When is the onset of autosomal dominant inheritance?

Which types of mutations does it arise from?

A

Onset is later than autosomal recessive

Can arise from de novo mutations

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17
Q

What is the typical onset of autosomal recessive inheritance?

What is the percent chance to be affected?

A

Onset is frequently early in life

25%

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18
Q

How does X-linked recessive inheritance work?

A

The carrier mother will pass down the gene to her daughter that will have 25% chance of obtaining the gene or being normal while the son will have a 25% chance of being affected or normal

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19
Q

What is X-activation- Lyonization?

What percentage is activated?

How is progeny affected?

A

Females have one active X chromosome the other X chromosome is inactivated and converted into a Barr Body

After inactivation all the descendants of that cell will have the same chromosome inactivated

12-20% of the inactivated X chromosome will be activated

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20
Q

What are common mutations in genes encoding structural proteins that have effects on the eye?

Are they dominant or recessive?

A

Marfan Syndrome (Autosomal dominant)

Ehlers Danlos Syndrome (Autosomal dominant and Autosomal recessive)

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21
Q

Which type of Ehler’s Danlos disorder includes both enzymes and proteins?

A

Ehlers Danlos Syndrome (Autosomal recessive)

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22
Q

Which type of mutation is found in Marfan syndrome?

What are the major tissues affected in Marfans?

How common is this disorder?

How is Marfan’s acquired?

A

Mutation in FBN1 gene encoding fibrillin

Skeleton, eyes and cardiovascular system are affected

Occurs 1/5000 people thus it is uncommon

70-85% of cases are familial while the rest are sporadic arising from de novo FBN1 mutations in germ cells of parents

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23
Q

How is fibrillin made and what is it used for?

A

Fibrillin is secreted by fibroblasts and incorporated into microfibrils which provide a scaffold for elastin

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24
Q

Which organ systems are affected from Marfan Syndrome?

A

Skeletal, Cardiovascular, and Ocular

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25
Q

What are characteristics of the skeletal system being affected in Marfan syndrome?

A

Tall with long arms and legs
Arachnodactyly
Pigeon Breast Deformity
Deeply depressed sternum
Kyphosis
Scoliosis
Joint Laxity

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26
Q

What are characteristics of the cardiovascular system being affected in Marfan syndrome?

A

Mitral Valve prolapse
Aortic Aneurysm
Acute Aortic Dissection (Can bleed to death!!)

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27
Q

What are characteristics of the ocular system being affected in Marfan syndrome?

A

Ectopia lentis (subluxation of the lens) and chorioretinal degeneration- This causes displacement of the lens since the elastin in zonules are affected

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28
Q

What is the result of abnormal fibrillin found in Marfan Syndrome?

A

Abnormal fibrillin leads to reduced sequestration of TGF-B -> excess TGF-B-> abnormal vascular smooth muscle development and matrix production

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29
Q

Which type of drug can inhibit TGF-B?

A

Angiotensin II Receptor Blockers which inhibit TGF-B signaling
ie: Losartin have been shown to improve aortic & cardiac function

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30
Q

What are the effects of Marfan Syndrome on the eye?

A
  • Enlargement of the globe due to scleral stretching -> longer axial length = myopia

-Flattened but not thinned cornea

-Dislocation of the lens

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31
Q

What is Ehlers-Danlos syndrome?

How many variants are there of Ehlers?

Which body parts are normally affected?

Which body process is poor due to Ehlers?

What are Ehlers-Danlos clinical features?

A
  • Group of diseases due to defects in collagen synthesis
  • Six variants due to distinct mutations
  • Skin, ligaments, joints
  • Wound healing
  • Fragile, hyperextensible skin due to trauma, hypermobile joints, (colon, cornea, large artery- ruptures)
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32
Q

What is an autosomal recessive variant of EDS (Ehlers-Danlos)?

What occurs due to this?

A

Deficiency of the lysyl hydroxylase enzyme

  • The lysyl hydroxylase enzyme is missing and is needed for hydroxylation of lysine residues during collagen synthesis.
  • Hydroxylysine is needed for cross-linking of collagen fibers
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33
Q

What are the autosomal dominant variants of EDS (Ehlers-Danlos)?
- What is affected/ symptoms?

A

Deficiency of type III collagen due to mutations affecting COL3AI gene
- Blood vessels, and bowel wall

Deficient synthesis of type V collagen due to mutations in COL5A1 and COL5A2
- Classical EDS

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34
Q

What are the ocular manifestations of Ehlers- Danlos syndrome?

A

Eye is 80% collagen
Keratoconus
High myopia
Blue Sclera
Lens Subluxation
Angioid Streaks
Posterior Sytaphloma
Corneal Rupture

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35
Q

What are the mutations in genes encoding receptor proteins or channels?

Which type of mutation is it?

A

Familial Hypercholesterolemia- Autosomal Dominant

Cystic Fibrosis- Autosomal Recessive

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36
Q

Which type of mutation causes hypercholesterolemia?

Why do patients develop hypercholesteremia?

What do heterozygotes have and what are they at risk of (%) Which disease is formed?

What do homozygotes have and what are they at risk of (%)
- What do they they develop and by what age do they die?

A

LDLR gene mutations encoding low density lipoprotein receptor (LDL)

Due to impaired transport of LDL into cells

Heterozygotes have elevated serum cholesterol which increases the risk of atherosclerosis (2-3 fold) -> Coronary Artery Disease

Homozygotes have an even greater increase in serum cholesterol (5 fold) -> Ischemic heart disease
-Cutaneous xanthomas and die by 20yo due to myocardial infarction

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37
Q

What is a common deposit of hypercholesterolemia?

How common is this mendelian disorder?

A

Cholesterol

1/500 thus it is the MOST common

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38
Q

Which type of mutation causes cystic fibrosis?

What is the principal defect?

What does cystic fibrosis result in ?

A

Autosomal recessive due to CFTR gene mutations encoding the CF transmembrane regulator

Principal defect is chloride ion transport resulting in high salt concentrations in sweat and in viscous luminal secretions in respiratory and GI tracts

CFTR mutations can be severe △F508 resulting in multisystem disease, or mild with limited disease extent and severity

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39
Q

How common is CF?

What is CF known as genetically?

A

1/3200 live births

Most common lethal genetic disease affecting white population

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40
Q

What are the clinical manifestations of CF?

A
  1. Cardiopulmonary complications (most common)
  2. Pulmonary Infections (resistant pseudomonads)
  3. Pancreatic insufficiency
  4. Infertility
  5. Liver Disease
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41
Q

What is a consistent characteristic of CF?

A

High level of sodium chloride in the sweat is a consistent and characteristic biochemical abnormality in CF

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42
Q

What is a ring of deposits of cholesterol on the eye called?

What age group is it common in?

A

Arcus around the limbus

Common for elderly

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43
Q

What does the CFTR channel do?

What follows it?

A

It transport chloride from the
Ductal lumen -> intersitium tissue

Na follows Cl

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44
Q

What occurs if there is a mutation of the CFTR channel?

A

Chloride will remain in the duct and there will be more NaCl on the surface in the ductal lumen

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45
Q

What occurs in the lungs of a cystic fibrosis patient?

A

Chloride remains in the duct with an excess of sodium and water
Since the Cl can’t leave the mucus is dehydrated which can lead to an increase in the development of infections
- Mucus normally protects the lungs but here it can’t since it is dehydrated

46
Q

Defect in CFTR causes what?

A

Corneal Edema in the corneal endothelium due to hydration in the endothelium

47
Q

What type of infection can cystic fibrosis form?

A

Pseudomonas infection with lots of mucus

48
Q

What is the criteria for diagnosing cystic fibrosis?

A
  • 1+ characteristic phenotypic features
    OR
  • History of cystic fibrosis
    OR
  • Positive newborn screen test result + increased sweat chloride concentration on 2+ occasions
    OR
  • Identification of 2 cystic fibrosis mutations OR
  • Demonstration of abnormal epithelial nasal ion transport
49
Q

Which types of diseases do mutations in genes encoding enzyme proteins causes?

Which type of inheritance pattern do they have?

A

Phenylketonuria
Galactosemia
Lysosomal Storage Diseases
Glycogen Storage Diseases

  • All diseases are autosomal recessive
50
Q

Which enzyme deficiency causes phenylketonuria (PKU)?
-What is the enzymes normal fucntion?

Which types of populations is it common/ uncommon in?

What are clinical features of untreated PKU?

What foods cause PKU and what are these foods high in?

A

Phenylalanine Hydroxylase deficiency which can’t metabolize phenylalanine -> tyrosine

Common in Scandinavian descent and is uncommon in African American/ Jewish populations

Clinical features: severe mental retardation, seizures, decreased pigmentation of skin

Foods: Meat, Fish, eggs, dairy, legumes, nuts and aspartame are high in phenylalanine

51
Q

How often does PKU affect births?

What happens if a female patient with PKU discontinues dietary treatment?

A

1/10,000 white infants

  • Female patients w/ PKU who discontinue dietary treatment can give birth to children with malformations and neurologic impairment resulting from transplacental passage
52
Q

What is galactosemia caused by?

What is accumulated?

How often are people affected?

What are the clinical features of galactosemia?

Which dietary restriction can prevent severe complications?

A

Caused by lack of galactose-1- phosphate uridyltransferase (GALT) enzyme

Galactose-1-phosphate & metabolites (galactitol) accumulation

1/60,000 affected thus it is rare

Clinical Features: Jaundice, liver damage, cataracts, neural damage, vomiting, diarrhea, and E.coli

Dietary restriction of galactose

53
Q

What causes lysosomal storage disease?

A

Accumulation of partially degraded insoluble metabolites within the lysosomes

54
Q

What are examples of lysosomal storage diseases?

A
  1. Tay Sachs Disease
  2. Neimann- Pick Diseases type A/B
  3. Gaucher Disease
  4. Mucopolysaccharidoses
  5. Fabry’s Disease
55
Q

What causes Tay- Sachs disease?

What can this disease cause?

What age is death expected?

Which type of population is this disease found in?

Which type of inheritance is seen?

What are the ocular findings of Tay-Sachs?

A
  1. Inability to metabolize Gm2 gangliosides due to lack of a or B subunit of hexosaminidase.
    - Gm2 accummulate in the CNS
  2. Causes mental retardation, blindness, more weakness
  3. Death by 2-3 years old
  4. Common in Ashkenazi Jews
  5. Heterozygous carriers occurs 1/30 people
  6. Ocular: Cherry red spots, optic atrophy
56
Q

What causes Niemann- Pick disease?

How many types are there?

What is seen clinically?

What are the ocular findings of Niemann-Pick disease?

A

Deficiency of sphingomyelinase
More lipid stored in phagocytes within the liver, spleen, bone marrow, and lymph nodes

Type A and Type B

Enlargement of lymph nodes

Ocular: Cherry red spots, opaque retinal appearance, corneal stromal haze, lens opacification

57
Q

What is the difference between type A/type B in Niemann’s?

A

Type A has an accumulation of sphingomyelin in the nervous system which leads to neuronal damage

Type B has no neuronal damage

58
Q

What occurs in ganglion cells of a normal retina?

A

Sphingolipid metabolism

  1. GM2 Ganglioside
    • Beta hexosaminidase A with alpha/beta subunits
  2. GM3 Ganglioside
  3. Final degradation products
59
Q

What occurs in ganglion cells of a mutated retina?

What disease is this seen in?

Which gene is defective?

A

Mutated HEXA gene fails to produce alpha subunit of affected enzyme causing GM2 ganglioside to accumulate leading to cell destruction and associated abnormal ocular features

Tay Sachs Disease

HEXA Gene

60
Q

What occurs in normal ocular cells?

What type of cell does this occur in?

A

Sphingomyelin is converted to ceramide via acid sphingomyelinase

Lysosome

61
Q

What occurs in mutated ocular cells?

Which disease is this seen in ?

Which gene is defective?

Which enzyme is altered?

What can occur due to inactivation of this enzyme?

A

Sphingomyelin accumulates which causes a lack of ceramide production resulting in a loss of normal structure and function.

Niemann-Pick Disease

SMPD1 gene

Sphingomyelinase enzyme is altered

Complete inactivation leads to more severe type A
Partial inactivation leads to type B

62
Q

What occurs in Gaucher disease?

Which enzyme is affected?

What are the ocular findings?

A

Deposits formed anywhere due to lack of lysosomal enzyme:
- Accumulation of glucocerebroside in mononuclear phagocytic cells

Glucocerebrosidase

Ocular Findings: Deposits in the cornea, retina, ciliary body etc

63
Q

What happens in type 1 gaucher disease?

A

Affected phagocytes become enlarged and accumulate in liver, spleen, and bone marrow, causing hepatosplenomegaly and bone erosion

64
Q

What occurs in mucopolysaccharidoses?

What are clinical features?

When does death occur?

What are associated syndromes?
Which associated syndrome is worse?

A

Accumulation of mucopolysaccharides in many tissues including liver, spleen, heart, blood vessels, brain, cornea, and joint

Coarse facial features,
Childhood death

Hunter syndrome= mild clinical course
Hurler syndrome= lethal clinical course: -
- Corneal clouding, coronary arterial and
valvular deposits

65
Q

What happens in type 2/3 Gaucher disease?

A

Variable neuronal development

66
Q

What are symptoms of hurler syndrome?

A

Corneal clouding, coronary arterial and valvular deposits

67
Q

What occurs in patient with Gaucher disease and mutated ocular cells?

Which gene is defective?

A

Mutated GBA causes glucocerebroside to accumulate leading to cell damage and associated abnormal ocular features

GBA gene defective

68
Q

What are symptoms of hunter syndrome?

A

Nose becomes broad
Tongue enlarged
Cheeks become enlarged and rounded
Lips thicken
Enlarged head
Hearing Loss
Heart valve disease
Stiffness in joints
Restricted growth
Compressed and damaged spinal cord

69
Q

What causes glycogen storage diseases?

Which organ/ tissue does this occur in?

A

Inherited deficiency of enzymes involved in glycogen metabolism which results in storage of normal or abnormal forms of glycogen

Occurs in liver or muscles in all tissues

70
Q

What occurs in Von Gierke disease?

Which type of form is this?

Which storage disease is this associated with?

A

Liver cells store glycogen because of a lack of hepatic glucose-6-phosphatase

Hepatic form

Glycogen Storage Disease

71
Q

What occurs in McArdle disease?

Which type of form is this?

Which storage disease is this associated with?

A

Muscle phosphorylase lack gives rise to storage in skeletal muscles and cramps after exercise

Myopathic form

Glycogen Storage Disease

72
Q

What occurs in Pompe disease?

Which enzyme is missing?

Which storage disease is this associated with?

How many people are affected

A

Lack of lysosomal acid maltase, all organs are affected by heart involvement is predominant

Maltase

Glycogen Storage Disease

1/60,000 live born infants

73
Q

What are multifactorial disorders caused by?

What is inherited in a multifactorial disorder?

Which diseases is a multifactorial disroder?

A

Caused by interactions between variant forms of genes and environmental factors

Collective inheritance of many polymorphisms

Type 2 diabetes mellitus, Obesity

74
Q

What are polymorphisms?

Are polymorphisms disease specific?

A

A genetic variant that has at least two alleles and occurs in at least 1% of the population

Sometimes, they are common to multiple diseases of the same type or disease specific

75
Q

What are chromosomal disorders?

Which type of chromosomes are affected?

How many people are affected?

What diagnoses chromosomal disorder?

A

Alterations in the number or structure of chromosomes

Autosomes or sex chromosomes

1/200 newborn infants have chromosomal abnormality

Cytogeneticist use karyotyping

76
Q

How would you identify 22q11.2 on a karyotype?

A
77
Q

Which arm is the short arm on a chromosome?

Which arm is the long arm on a chromosome?

A

Short p arm

Long q arm

78
Q

What are the patterns of chromosomal rearrangement?

A

Translocation
Isochromosomes
Deletions
Inversions
Ring Chromosome

79
Q

What happens in a centric fusion/ Robertsonian chromosome rearrangment?

A

Loss of genetic information because chromosome is not balanced and too long

80
Q

What is the difference between a paracentric and pericentric inversion?

A

In paracentric inversions there is a change of genetic info on the same side of the centromere

In pericentric inversion there is a swap of genetic info to different sides of the centromere

81
Q

What is Fabry’s Disease caused from?

Which type of inheritance is seen?

What is built up in Fabry’s disease?

What characterizes Fabry’s disease?

A

Caused by lack of enzyme: alpha-galactosidase A (alpha-GAL)

X linked inheritance

Glycosphingolipids are built up

Characterized by:
1. Episodes of pain in the hands and feet
2. Clusters of small, dark red spots on the skin
3. Decreased ability to sweat (Hypohidrosis)
4. Corneal Verticillate, lens opacities, and retinal vascular abnormalities
5. Hearing loss
6. Kidney and heart disease

82
Q

Which type of corneal build up is an effect of Fabry’s disease?

A

Corneal Verticillata- whirl like patterns are found which causes optic atrophy

83
Q

What are the general features of chromosomal disorders?

A
  1. Associated with absence, excess, or abnormal rearrangements of chromosomes
  2. Disorders can occur from de novo changes- EXCEPT down syndrome
84
Q

Is loss or excess chromosomal material result in more severe defects?

Which is worse imbalance of sex chromosomes or autosomes?

Which sex chromosome has less genes?

A

Loss of chromosomal material produces more severe defects

Autosomes are worse- imbalance of sex chromosomes (excess or loss) are tolerated much better than similar imbalances of autosomes and are NOT lethal because you have two sex chromosomes.

Y chromosome

85
Q

What does excess chromosomal material result from?

A

Excess chromosomal material results form a complete chromosome (trisomy) or from part of a chromosome (robertsonian translocation)

86
Q

If the chromosomal disorder is de novo do the parents have a higher risk of having the same disorder in their next child?

A

NO, the risk of recurrence is low in siblings

87
Q

What are characteristics of sex chromosome disorders?

A

Sex chromosomal disorders often produce subtle abnormalities, sometimes not detected at birth. Infertility, a common manifestation, cannot be diagnosed until adolescence

88
Q

What is an example of a chromosomal disorder involving autosomes? Which type of mutation does this occur from?

A

Down Syndrome

22q11.2 Deletion syndrome

89
Q

Which is the most common chromosomal disorder?

What is this disorder associated with?

How many chromosomes would you have?

What are characteristics of down syndrome?

A

Down Syndrome Trisomy 21

Extra copy of genes on chromosome 21 or an extra long arm of chromosome 21

47 chromosomes

Severe mental retardation, flat facial profile, epicanthic folds, cardiac malformations, higher risk of leukemia and infections, and premature development of Alzheimer disease

90
Q

In down syndrome what is the associated chromosome count most due to? (Mutation wise)

A

95% Meiotic nondisjunction
4% Robertsonian translocation
1% Mosaics

91
Q

What happens during meiotic nondisjunction?

Which percent of down syndrome does this make up?

Which type of mutation is this called?

A

The chromosomes fail to separate properly during meiosis causing non-disjunction meiosis thus you have an extra chromosome

95%

Meiosis non disjunction

92
Q

What happens during Robertsonian translocation?

What % does this occur in for down syndrome?

Which type of mutation is this called?

How many chromosomes are found?

A

Chromosomes 14 & 21 swap material resulting in chromosome 14 having an extra long arm

4%

Translocation

46- one chromosome has an extra long arm

93
Q

What makes down syndrome more prevalent?

How often does this occur?

What are the chances in young age vs old age?

What is the average death age of down syndrome patients? What is the cause?

A

Maternal age

1/1550 live births for women <20yo
1/25 live births for women >45yo

The older you are the likelier you are to have a baby with down syndrome

47yo due to heart disease

94
Q

What is the most common ocular finding for patients with down syndrome?

A

Brush field spots

95
Q

What is DeGeorge syndrome also known as?

Which chromosome is affected?

What are patient’s at high risk for?

A

22q11.2 Deletion Syndrome or velocardiodfacial syndrome

Chromosome 22

Psychoses ie: schizophrenia and bipolar disorder

96
Q

What are the clinical manifestations of DeGeorge syndrome?

A

Thymic hypoplasia with diminished T cell immunity and parathyroid hypoplasia with hypocalcemia

Congenital heart disease involving outflow tracts, facial dysmorphism and developmental delay

97
Q

What are the facial features of 22q11.2?

A

Long face with flattened malar eminences, narrow palpebral fissures, prominent nose and small downturned mouth

98
Q

What are the disorders involving sex chromosomes?

What are their associated karyotypes?

Are disorders with sex chromosomes lethal? Why?

Which chromosome is most tolerated and why?

A

Klinefelter Syndrome and Turner Syndrome

Klinefelter: 45,X Turner: 49, XXXXY

No, they are both compatible with life. Because, X inactivation aka LYONIZATION and the small amount of genetic information carried by the Y chromosome

Extra Y chromosomes because the only information known to be carried on the Y chromosome is to determine male gender

99
Q

What is the lyonization hypothesis?

Which arm of the chromosome escapes lyonization?

A

In females, one X chromosome maternal or paternal is randomly inactivated during development

21% of genes on “p arm” escape inactivation and 3% on “q arm” escape

100
Q

How does Klinefelter syndrome develop?

What does the karyotype look like?

How is the disorder inherited? (which parent)

How many births does it affect?

What are the clinical manifestations?

A

Develops when there are 2+ X chromosomes and 1+ Y chromosomes in males

47, XXY 46,XY/47,XXY & 47,XXY/48,XXXXY

Extra X chromosome can be maternal or paternal

1 in 660 male births

Testicular atrophy, sterility, reduced body hair, gynecomastia, eunuchoid body habitus (feminine features)

101
Q

What is the most common karyotype for patients with Klinefelter’s?

What is the mutation that occurs?

Which types of patterns are seen (%)?

A

47, XXY

Nondisjunction of sex chromosomes during meiosis

Mosaic patterns- 15%

102
Q

How does Turner syndrome arise?

How many births are affected?

What are physical appearances of people with turner’s?

A

Partial or complete monosomy of X chromosome

1 in 2000 female births

Webbing of neck, cubitus valgus, cardiovascular malformations, Amenorrhea, lack of secondary sex characteristics, fibrotic ovaries

103
Q

What are the most common chromosome mutations with Turner’s?

A

57% missing entire X chromosome 45,X

14% abnormal X (deletion of short arm which results in isochromosome of the long arm)

30% mosaics (closest to normal)

104
Q

What are single gene disorders with atypical patterns of inheritance?

A
  1. Diseases due to triplet repeat mutations
  2. Diseases due to mutations in mitochondrial genes
  3. Diseases with alteration of imprinted regions of the genome
105
Q

How many diseases are caused by triplet repeat mutations?

What are examples?

A

40 diseases

  1. Fragile X syndrome
  2. Huntington Disease
106
Q

What is Fragile X syndrome caused by?

What is the FMRP gene useful for?

What does the FMR1 gene contain? (mutation)

What happens if the FMR1 gene is abnormally methylated?

A

Mutation in the FMR1 gene

FMRP- RNA binding protein that is essential for normal cognitive development and female reproductive function

CGG repeats in the 5’ untranslated region normal-29, Fragile X= 200-4000 repeats

Transcriptional suppression of FMR1

107
Q

What is Huntington Disease caused by?

What does this disease give rise to?

A

Mutations in CAG repeats in the coding region

Gives rise to misfolded proteins that interfere with function of normal proteins

108
Q

What is a disease caused by mutations in mitochondrial genes?

Which type of inheritance is seen with these diseases?

Which types of organs are most affected?

What do the mitochondrial genes code for?

What are the clinical manifestations seen with Leber’s?

A

Leber Heriditary optic neuropathy

Maternal inheritance

Organs depending on oxidative phosphorylation (skeletal muscle, heat, brain)

MT-ND1,- ND4, -ND6 all code for NADH dehydrogenase protein

Sever optic atrophy and permanent decrease of visual acuity -> blind

109
Q

What are the diseases associated with altering the imprinted regions of the genome?

Which type of deletion is each syndrome associated with?

What are the clinical manifestations of each?

A
  1. Prader- Willi Syndrome- Deletion of paternal chromosomal region 15q12
  2. Angelman Syndrome- Deletion of maternal 15q12

Paternal (PW): Mental retardation, short stature, hypotonia, obesity, hypogonadism

Maternal (AS): Mental retardation, ataxia, seizures, inappropriate laughter

110
Q

What is the effect of genomic imprinting on genes?

What is imprinting associated with?

A

Genomic imprinting causes inactivation of paternal or maternal alleles which causes different clinical manifestations

Methylation of the gene promoter

Human Bioscience II (8 decks)

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