CBCL 2 Flashcards
Prader-Willi syndrome is a result of?
Maternal imprinting: Gene from mom is normally silent and paternal gene is deleted.
Allele e4 in AD is thought to have what effect?
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.
Mutations in APP, PSEN1 and PSEN2 has what affect on β-amyloid precursor protein?
increase the relative or absolute production of Aβ 42/43
Type I diabetes shows what type of inheritance?
Multifactorial
What is the inheritance of Long QT syndrome?
Autosomal dominant (Romano-Ward syndrome) and autosomal recessive (Jervell and Lange-Nielson Syndrome)
What is the inheritance of Achondraplasia?
Autosomal dominant
What are some of the important genes associated with Type II diabetes?
PPARG (Mexican Am and Finnish) HNF4A (MODY) GCK CF7L2 (Icelandic Population)
What genes would be examined that could be implicated as a direct cause of early-onset Alzheimers disease?
APP, PSEN1, and PSEN2
What are the two genetic diseases linked to genetic imprinting?
Prader-Willi syndrome and Angelman Syndrome
What is the important genotypic characteristic associated with Fragile X?
Triplet repeat expansion (CGG repeats >200; normal is 6-50) and sex specific anticipation
Down syndrome is a result from?
Trisomy 21
The MTHFR affects what two diseases?
Coronary Artery Disease and Neural Tube defects
What is the inheritance of Fragile X syndrome?
X-linked
What is the important gene associated with Fragile X?
FMR-1
What is the inheritance of Marfan Syndrome?
Autosomal dominant and has dominant negative characteristics
What locus is associated with a 30-60% genetic susceptibility in type I diabetes?
HLA locus
What type of inheritance can Alzheimer’s display?
Autosomal dominant or multifactorial
What are the clinical features of Patau syndrome?
Cleft lip/palate, holoprosencephaly, and polydactyly
Early onset Alzheimers shows what type of inheritance?
Autosomal dominant
What is the important genotypic characteristic associated with Down Syndrome?
Trisomy 21
20-70% of patients with autosomal dominant have mutations in what gene?
PSEN1
What causes Long QT syndrome?
Cardiac Ion channel mutations leading to repolarization defects
What are the phenotypic characteristics with NTDs?
High homocysteine levels and needed to treat with folic acid
What is the phenotypic presentation of Hirschsprung disease?
Absence of nerve cells normally present in the wall of the large bowel and required for normal peristalsis abdominal distension
What is the protective allele associated with Type I diabetes?
DR2
Patau syndrome is a result of?
Trisomy 13
What is the reason behind researchers believe there is a genetic component to Type II diabetes?
Monozygotic twins have a 69 to 90% have a much higher rate of disease vs dizygotic twins 24 to 40%
Why is the APOE genotype not useful for predicting the Alzheimer’s phenotype in asymptomatic individuals?
APOE has poor positive and negative predictive value.
What is the inheritance pattern associated with Hirschsprung disease?
Autosomal dominant, autosomal recessive and multifactorial
What is the difference between the e4 and the e2/e3 alleles?
Contains Arg at both position 112 and 158 of the apolipoprotein. This leads to increased risk for alzheimer’s.
What is the cause of achondraplasia?
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
What are the clinical features of Down Syndrome?
Flat facies, single palmar crease, congential heart diseases, a gap between first and second toes.
What are the clinical features of Edwards syndrome?
Severe intellectual disability, low-set ears, micrognathia, and death w/in a year.
What is the inheritance pattern and important genes associated with cystic fibrosis?
Autosomal recessive and CFTR
What is the inheritance of Type II diabetes?
Multifactorial and polygenic
What is the important gene associated with Achondraplasia?
FGFR3
What is important to monitor in Marfan syndrome?
Aortic root dilation and other connective tissue disorders
What is the term for twins who suffer from the same disease?
Concordant
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?
Post-mitotic APP dinucleotide deletion mutations
How is the inheritance between siblings that are monozygotic twins vs normal siblings?
1 in 14 if there is a sibling with it and 1 in 3 if they are monozygotic twins
What are the hallmarks associated with FH?
Accumulation of plasma LDL, decreased LDL hepatic clearance , foam cell production and rupture, thrombus formation, atherosclerosis
What is the major genetic characteristics of Huntington disease?
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
What are the linkage disequilibrium alleles associated with Type I diabetes?
DR3, DR4, and DQ
What is the underlying etiology of Type I diabetes?
Autoimmune destruction of Islet β cells in the pancreas triggered by unknown mechanism
Angelman syndrome is a result of?
Paternal imprinting: gene from dad is normally silent and maternal gene is deleted
Alzheimer’s disease is caused by what?
Aβ 42/43 aggregates in the brain
Familial Hypercholesteremia show what type of inheritance?
Autosomal dominant
What is the role of APP in AD?
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.
What causes Hirschsprung disease?
Failure of neural crest derived intestinal ganglion cells to migrate to intestinal tract at appropriate time in development
Huntington disease has what type of inheritance pattern?
Autosomal dominant
What is the important gene associated with Marfan Syndrome?
FBN-1 encodes for fibrillin in tissues
Edwards syndrome is a result from?
Trisomy 18
