CBCL 2

Question 1

Prader-Willi syndrome is a result of?

Answer 1

Maternal imprinting: Gene from mom is normally silent and paternal gene is deleted.

Question 2

Allele e4 in AD is thought to have what effect?

Answer 2

both familial AD and sporadic late-onset AD are strongly associated with allele ε4 at the apolipoprotein E gene ( APOE; see Chapter 8 ). The frequency of ε4 is 12% to 15% in normal controls compared with 35% in all patients with AD and 45% in patients with a family history of dementia.

Question 3

Mutations in APP, PSEN1 and PSEN2 has what affect on β-amyloid precursor protein?

Answer 3

increase the relative or absolute production of Aβ 42/43

Question 4

Type I diabetes shows what type of inheritance?

Answer 4

Multifactorial

Question 5

What is the inheritance of Long QT syndrome?

Answer 5

Autosomal dominant (Romano-Ward syndrome) and autosomal recessive (Jervell and Lange-Nielson Syndrome)

Question 6

What is the inheritance of Achondraplasia?

Answer 6

Autosomal dominant

Question 7

What are some of the important genes associated with Type II diabetes?

Answer 7

PPARG (Mexican Am and Finnish) HNF4A (MODY) GCK CF7L2 (Icelandic Population)

Question 8

What genes would be examined that could be implicated as a direct cause of early-onset Alzheimers disease?

Answer 8

APP, PSEN1, and PSEN2

Question 9

What are the two genetic diseases linked to genetic imprinting?

Answer 9

Prader-Willi syndrome and Angelman Syndrome

Question 10

What is the important genotypic characteristic associated with Fragile X?

Answer 10

Triplet repeat expansion (CGG repeats >200; normal is 6-50) and sex specific anticipation

Question 11

Down syndrome is a result from?

Answer 11

Trisomy 21

Question 12

The MTHFR affects what two diseases?

Answer 12

Coronary Artery Disease and Neural Tube defects

Question 13

What is the inheritance of Fragile X syndrome?

Answer 13

X-linked

Question 14

What is the important gene associated with Fragile X?

Answer 14

FMR-1

Question 15

What is the inheritance of Marfan Syndrome?

Answer 15

Autosomal dominant and has dominant negative characteristics

Question 16

What locus is associated with a 30-60% genetic susceptibility in type I diabetes?

Answer 16

HLA locus

Question 17

What type of inheritance can Alzheimer’s display?

Answer 17

Autosomal dominant or multifactorial

Question 18

What are the clinical features of Patau syndrome?

Answer 18

Cleft lip/palate, holoprosencephaly, and polydactyly

Question 19

Early onset Alzheimers shows what type of inheritance?

Answer 19

Autosomal dominant

Question 20

What is the important genotypic characteristic associated with Down Syndrome?

Answer 20

Trisomy 21

Question 21

20-70% of patients with autosomal dominant have mutations in what gene?

Answer 21

PSEN1

Question 22

What causes Long QT syndrome?

Answer 22

Cardiac Ion channel mutations leading to repolarization defects

Question 23

What are the phenotypic characteristics with NTDs?

Answer 23

High homocysteine levels and needed to treat with folic acid

Question 24

What is the phenotypic presentation of Hirschsprung disease?

Answer 24

Absence of nerve cells normally present in the wall of the large bowel and required for normal peristalsis abdominal distension

Question 25

What is the protective allele associated with Type I diabetes?

Answer 25

DR2

Question 26

Patau syndrome is a result of?

Answer 26

Trisomy 13

Question 27

What is the reason behind researchers believe there is a genetic component to Type II diabetes?

Answer 27

Monozygotic twins have a 69 to 90% have a much higher rate of disease vs dizygotic twins 24 to 40%

Question 28

Why is the APOE genotype not useful for predicting the Alzheimer’s phenotype in asymptomatic individuals?

Answer 28

APOE has poor positive and negative predictive value.

Question 29

What is the inheritance pattern associated with Hirschsprung disease?

Answer 29

Autosomal dominant, autosomal recessive and multifactorial

Question 30

What is the difference between the e4 and the e2/e3 alleles?

Answer 30

Contains Arg at both position 112 and 158 of the apolipoprotein. This leads to increased risk for alzheimer's.

Question 31

What is the cause of achondraplasia?

Answer 31

GOF mutations that cause ligand-independent activation of FGFR3. Constitutive activation of FGFR3 inappropriately inhibits chondrocyte proliferation within the growth plate and consequently leads to shortening of the long bones as well as to abnormal differentiation of other bones

Question 32

What are the clinical features of Down Syndrome?

Answer 32

Flat facies, **single palmar crease**, congential heart diseases, a gap between first and second toes.

Question 33

What are the clinical features of Edwards syndrome?

Answer 33

Severe intellectual disability, **low-set ears,** micrognathia, and death w/in a year.

Question 34

What is the inheritance pattern and important genes associated with cystic fibrosis?

Answer 34

Autosomal recessive and CFTR

Question 35

What is the inheritance of Type II diabetes?

Answer 35

Multifactorial and polygenic

Question 36

What is the important gene associated with Achondraplasia?

Answer 36

FGFR3

Question 37

What is important to monitor in Marfan syndrome?

Answer 37

Aortic root dilation and other connective tissue disorders

Question 38

What is the term for twins who suffer from the same disease?

Answer 38

Concordant

Question 39

Inherited mutations in APP have been found only in a small percentage of families with early-onset AD. What is the cause for most cases of Alzheimer disease in the population?

Answer 39

Post-mitotic APP dinucleotide deletion mutations

Question 40

How is the inheritance between siblings that are monozygotic twins vs normal siblings?

Answer 40

1 in 14 if there is a sibling with it and 1 in 3 if they are monozygotic twins

Question 41

What are the hallmarks associated with FH?

Answer 41

Accumulation of plasma LDL, decreased LDL hepatic clearance , foam cell production and rupture, thrombus formation, atherosclerosis

Question 42

What is the major genetic characteristics of Huntington disease?

Answer 42

HD gene: CAG repeats Adult onset: 40-55 repeats Juvenile onset: \> 60 repeats Reduced penetrance: 36-39 repeats Triplet repeat expansion; anticipation with each generation

Question 43

What are the linkage disequilibrium alleles associated with Type I diabetes?

Answer 43

DR3, DR4, and DQ

Question 44

What is the underlying etiology of Type I diabetes?

Answer 44

Autoimmune destruction of Islet β cells in the pancreas triggered by unknown mechanism

Question 45

Angelman syndrome is a result of?

Answer 45

Paternal imprinting: gene from dad is normally silent and maternal gene is deleted

Question 46

Alzheimer's disease is caused by what?

Answer 46

Aβ 42/43 aggregates in the brain

Question 47

Familial Hypercholesteremia show what type of inheritance?

Answer 47

Autosomal dominant

Question 48

What is the role of APP in AD?

Answer 48

β-amyloid precursor protein (βAPP) undergoes endoproteolytic cleavage to produce peptides with neurotrophic and neuroprotective activities. Cleavage of βAPP within the endosomal-lysosomal compartment produces a carboxyl-terminal peptide of 40 amino acids (Aβ 40 ); the function of Aβ 40 is unknown. In contrast, cleavage of APP within the endoplasmic reticulum or cis -Golgi produces a carboxyl-terminal peptide of 42 or 43 amino acids (Aβ 42/43 ). Aβ 42/43 readily aggregates and is neurotoxic in vitro and possibly in vivo. Patients with AD have a significant increase in Aβ 42/43 aggregates within their brains.

Question 49

What causes Hirschsprung disease?

Answer 49

Failure of neural crest derived intestinal ganglion cells to migrate to intestinal tract at appropriate time in development

Question 50

Huntington disease has what type of inheritance pattern?

Answer 50

Autosomal dominant

Question 51

What is the important gene associated with Marfan Syndrome?

Answer 51

FBN-1 encodes for fibrillin in tissues

Question 52

Edwards syndrome is a result from?

Answer 52

Trisomy 18