Lecture 3: Mendelian Disease Part One

Question 1

What are amyloid plaques?

Answer 1

abnormal deposits of protein called beta amyloid that is found in the space between neurons

Question 2

What are neurofibrillary tangles?

Answer 2

formed by clumps of tau protein which is part of the structure of the microtubules that support the structure of the neuron

Question 3

What are the consequences of amyloid plaques and neurofibrillary tangles forming?

Answer 3

the synaptic connections between neurons are lost and many neurons stop function and die… atrophy of the brain occurs… this is common in Alzheimer’s Disease

Question 4

What inheritance pattern do most cases of early onset AD have?

Answer 4

autosomal dominant pattern

Question 5

What chromosomes are involved in the genetics of AD? Alzheimer’s Disease

Answer 5

1, 14, and 21

Question 6

What is amyloid precursor protein (APP gene)?

Answer 6

chromosome 21; over 30 mutations of this gene have been associated with early on-set AD

Question 7

How is chromosome 14 involved in Alzheimer’s disease?

Answer 7

chromosome 14 is presenilin 1 (PSN1); over 150 mutations of this gene have been identified; abnormalitites in this gene lead to overproduction of a longer and more toxic beta amyloid peptide and plaque formation

Question 8

What is the rarest of the three chromosomes associated with EOAD?

Answer 8

chromosome 1 or presenilin 2 (PSN2)

Question 9

When does late- onset Alzheimer’s typically occur?

Answer 9

after age 65

Question 10

What is the most firmly identified gene involved in late-onset Alzheimer’s?

Answer 10

apolipoprotein E (APOE)

Question 11

On what chromosome is APOE found?

Answer 11

chromosome 19

Question 12

What are the three alleles of APOE and what is their role in late-onset Alzheimer’s?

Answer 12

APOE epsilon 2- least common allele and appears to reduce risk
APOE epsilon 3- most common allele and has a neutral role in the disease
APOE epsilon 4- found in 10-15% of the population and appears to increase risk for AD and is associated with an earlier onset

Question 13

When is an individual at the highest risk for late-onset AD?

Answer 13

when a person has two copies of APOE epsilon 4

Question 14

What are epigenetics?

Answer 14

factors such as diet, chemical exposures and chronic illnesses can alter the DNA of genes causing certain genes to be switched on or off

Question 15

What is one process that can alter which genes are transcribed and which are not?

Answer 15

DNA methylation

Question 16

When can genetic testing in AD occur?

Answer 16

early-onset AD families may choose to be tested for the 3 genes that increase risk for early onset AD

Question 17

What type of inheritance is Huntington’s Disease?

Answer 17

autosomal dominant inheritance

Question 18

What % chance does a child of an individual with HD have of getting the disease?

Answer 18

50% chance

Question 19

What are the manifestations associated with Huntington’s disease?

Answer 19

chorea (rapid involuntary movements), gait abnormalities, abnormal slow eye movements, psychiatric abnormalities, loss of insight, memory loss, weight loss

Question 20

On which chromosome do HD genes exist?

Answer 20

chromosome 4

Question 21

What does the mutated form of HD gene consist of?

Answer 21

an expanded CAG trinucleotide repeat

Question 22

What is CAG the codon for?

Answer 22

glutamine

Question 23

What causes earlier onset and higher severity of HD?

Answer 23

the higher the number of CAG repeats

Question 24

What is the significance of inheriting the HD allele from the father?

Answer 24

there is a three year earlier onset of the disease

Question 25

What is a positive test result in HD?

Answer 25

more than 40 CAG repeats; always develops HD

Question 26

What is a negative test result in HD?

Answer 26

less than 35 CAG repeats

Question 27

What is the most common lethal inherited disorder among Caucasians in the U.S.?

Answer 27

cystic fibrosis

Question 28

How is cystic fibrosis inherited?

Answer 28

in an autosomal recessive patter; both copies of gene must be present for disease

Question 29

Cystic fibrosis is caused by a defect on which gene?

Answer 29

chromosome 7; cystic fibrosis transmembrane conductor regulator (CTFR)

Question 30

What is the purpose of the CTFR gene?

Answer 30

helps regulate chloride channels in epithelial cells; channels allow for chloride to be excreted and excess sodium uptake is inhibited; water content of secretions is maintained

Question 31

What happens a patient with CF in regards to the chloride transport system?

Answer 31

defective chloride transport across the membrane and enhanced sodium absorption causes increase in water absorption

Question 32

What are the manifestations of cystic fibrosis?

Answer 32

failure to thrive/ impaired growth, chronic pulmonary infections, nasal polyps, chronic cough, abnormal lung parenchyma, right sided heart failure, pancreatic inflammation, steatorrhea (increased fat in stool), biliary cirrhosis, liver damage, portal hypertension

Question 33

What is significant about CF in males?

Answer 33

98% are infertile due to absence of vas deferens

Question 34

Which form of neurofibromatosis is more common?

Answer 34

NF1 is more common than NF2

Question 35

What is a neurofibroma?

Answer 35

a benign encapsulated tumor composed of Schwann cells tat are ectodermal in origin

Question 36

How many cases of NF1 are inherited and how many result from new mutations?

Answer 36

50% inherited | 50% new mutations

Question 37

What is the inheritance pattern of NF1?

Answer 37

autosomal dominant disorder

Question 38

What is NF1 gene main function?

Answer 38

tumor suppressor gene

Question 39

Does NF1 gene have complete penetrance?

Answer 39

Yes.

Question 40

What are café-au-lait macules?

Answer 40

they appear during the first year of birth and 6 or more is highly suggestive of NF1

Question 41

What are Lisch nodules?

Answer 41

small hamartomas of the iris; more common in adult NF1 patients

Question 42

What are a few manifestations of NF1?

Answer 42

cutaneous neurofibroma, plexiform neurofibroma, optic glioma; bony abnormalities like bowing of legs, scoliosis, short stature, and osteoporosis

Question 43

What is NF2?

Answer 43

cause development of noncancerous tumors on the auditory and vestibular nerves of the body; tumors are known as schwannomas and are usually bilateral; tumors can occur in CNS; symptoms typically present later in life

Question 44

On what gene is the chromosome for NF2 found?

Answer 44

chromosome 22

Question 45

What does NF2 gene encode for?

Answer 45

protein called merlin (tumor suppressor gene)

Question 46

What is the inheritance pattern for NF2?

Answer 46

autosomal dominant inheritance

Question 47

How does polycystic kidney disease typically manifest?

Answer 47

as bilateral renal cysts but it can be a multi-organ disease

Question 48

How is polycystic kidney disease typically transmitted?

Answer 48

in an autosomal dominant pattern; rarely follows an autosomal recessive pattern

Question 49

What are the mutations for polycystic kidney disease?

Answer 49

PKD1 or PKD2

Question 50

On which chromosome is PKD1 located and what does it encode for?

Answer 50

chromosome 16 and encodes for polycystin-1

Question 51

What is the difference between PKD1 and PKD2?

Answer 51

PKD1 is 85% of the disease and has increased severity of symptoms; PKD1 also has younger onset of symptoms

Question 52

On which chromosome is PKD2 located and what does it encode?

Answer 52

on chromosome 4 and it encodes polycystin-2