Lecture 7: Molecular Detection of Inherited and Metabolic Diseases Flashcards
Type of mutations that are inherited from a parent and are present throughout a person’s life in virtually every cell in the body
Inherited (germ line)
-These mutations are also called germline mutations because they are present in the parent’s egg or sperm cells, which are also called germ cells.
Type of mutation that occurs at some time during a person’s life
-present in only certain cells, not in every cell in the body
-These changes can be caused by environmental factors such as ultraviolet radiation from the sun, or can occur if a mistake is made as DNA copies itself during cell division
Acquired (somatic/sporatic)
-Acquired mutations in somatic cells (cells other than sperm and egg cells) cannot be passed on to the next generation
Types of mutations at the chromosome level
- Deletions
- Duplications
- Inversions
- Translocations t[#,#]
encodes a cytoplasmic tyrosine kinase
C-abl
promotes oligomerization
Bcr
promotes activation of
abl by oligomerization induced autophosphorylation
Bcr-abl fusion
What is the most common variant with Burkitts Lymphoma?
T(8;14)(q24;q32)
What is Burkitts lymphoma associated with?
the Epstein-Barr Virus
(EBV) in nearly 100% of cases in endemic form in central Africa.
* In the sporadic forms (occur in Western countries), EBV is present in approximately 30% of cases and in 40% of immunodeficiency-associated
cases
Burkitts Lymphoma T(8;14)(q24;q32):
______ is brought under the
transcriptional control of the IG enhancer elements leading to its constitutive transcriptional deregulation
MYC
Base substitutions (Point Mutation)
* ____________ (purine for purine, pyrimidine for pyrimidine)
* ____________ (purine for pyrimidine)
transition
transversion
Type of mutation:
amino acid Condon to “stop”
Nonsense mutations
What are the three stop codons?
UAA, UAG, UGA
A genetic variant which results in a shorter version of the protein being produced
Truncated protein
Example of nonsense mutation
Thalassemia
* beta-thalassemia in Sardinia, Codon 40, CAG (Gln) to TAG (stop), Mutation associated with Low LDL
* alpha-thalassemia: Constant Spring: from stop codon to glutamine @ 142 (TAA to CAA)
Multiple gene deletions also termed
CATCH 22
Multiple gene deletions:
What does CATCH 22 an acronym for?
Microdeletions in chromosomal region
22q11.2 (CATCH 22)
cardiac defect, abnormal
facies, T-cell deficit, cleft palate, and hypocalcemia.
What are two examples of multiple gene deletions?
-DiGeorge syndrome
-Velocardiofacial syndrome
Frame-Shift mutations are _____________, not multiple of 3bp
insertion/deletion
Examples of frame-shift mutations
e.g., Tay Sachs 4 bp insertion,
* BRCA1 185 delAG, BRCA2 6174delT, etc.
* Blood group O (1 bp deletion)
What are other types of mutations?
- Cap-site Mutants
- Mutations in initiation codons
- Creation of a new initiation codon
- Mutations in termination codons
- Polyadenylation/cleavage signal mutations.
Factor V Leiden Pathophysiology:
In the normal person, factor V functions as a cofactor to allow factor _____ to activate an enzyme called thrombin. Thrombin in turn cleaves
fibrinogen to form fibrin, which form the fibrin clot.
Xa
Factor V Leiden Pathophysiology:
Activated protein _______ is a natural anticoagulant that acts to limit the extent of clotting by cleaving and degrading factor V.
C (aPC)
Factor V Leiden Pathophysiology:
The excessive clotting that occurs in this disorder is almost always restricted to the…
veins, where the clotting may cause a deep vein
thrombosis (DVT)
How common is Factor V Leiden in Caucasians in North America?
5%
