DNA Based Diagnostics- Lecture 9/28/21 Flashcards
Silent mutation
The vast majority of mutations, happen randomly and will never know
Germ line mutations
Heritable, could be any cell in the body
Somatic mutations
Acquired, can’t be passed on, only in certain tissue
Specimens used for genetic testing
- Whole blood (hereditary diseases)
- Saliva (alternatives to blood)
- Blood cards (hereditary diseases)
- Fibroblasts (hereditary diseases)
- Solid organ tissue/biopsies (solid cancer)
- Bone marrow (hematologic malignancies)
- Hair (crime scene)
Silent mutation
Mutation that does not alter gene product
Missense mutation
Mutation that alters one amino acid
Nonsense Mutation
Inserts a stop codon
Muscular dystrophy
Disease caused by deletion, disease severity determined by the amount of missing (normal) dystrophin
Tandem repeat sequences examples
Huntington and Fragile X
Insertions
Large range, can be very serious and alter gene product
Frameshift mutation
Caused by insertion or deletion not in groups of three
Splice site mutations
Mutation in GT or AG site of the introns, causes splicing issues
Null mutation
Loss of function, classic AR, one allele sufficient
Haploinsufficiency
AD/ incomplete dominant, heterozygous show more mild disease
Phenylketonuria
Classic null mutation, missing the enzyme that turns phenylalanine to tyrosine
Familial hypercholesterolemia
Example of haploinsufficiency, heterozygotes show slightly elevated LDL concentration
Dominant negative
Loss of function, common in proteins that play a role in structural elements, mutant unit diminishes all
Osteogenesis imperfecta
Defect in collagen 1, classic example of dominant negative
Gain of function
Always dominant, new or enhanced activity of the protein
DNA diagnostic methods (4)
- PCR
- Short tandem repeat polymorphism test
- Sanger sequencing
- Next-generation sequencing
Benefits of DNA-based testing (5)
- Diagnistic identification or clarification
- Presymptomatic diagnostic
- ID of predisposition
- Prognostic prediction
- Treatment decisions
Challenges of DNA-based testing
- Social stigma
-Unravelling non-paternity - Pregnancy termination
- Info overload
- Results of unknown significance
-negative results
Costs vs benefits
