Week 2 Flashcards
Treatment of Multiple Endocrine Neoplasia
genetic predisposition to a variety of tumors
Prophylactic thryoidectomy shows increased survival rate
Treatment of Alpha1 antitrypsin deficienty
recombinant protein replacement therapy to replace extracellular protein
Gene Therapy
introduction of DNA or RNA into human cells to treat acquired or inherited disease Ex vivo (insert outside the patient in cells/tissues which are then given to patient In vivo (DNA/RNA is injected into patient)
Retroviral Gene Therapy
RNA viruses
Integrates into the cell genome with minimal host immunge reactions.
Insert size is limited to 7-8 kn and can infect only dividing cells.
There is a risk of insertional mutagenesis
efficient in infecting dividing cells
Integrate into genomic DNA so can get passed to daughter cells
Adenoviral Gene Therapy
DNA viruses
A: wide variety of cells can be infected, insert can be 35-36kb, stable and easy to get
D: does not integrate into genome, expression can be transient
lower risk of insertional mutagenesis, Severe immune reactions
can infect non-dividing cells,
short lived effect, not passed onto daughter cells
Non-Viral Gene Therapy
liposomes, direct DNA
large insert side, could deliver multiple ch, minimal host immune response.
There is very low effiiciency and transient epression.
The safest option because it doesn’t integrate into host genome
Often degraded by cellular mechanisms and effect is hsort lived.
Safety of three different gene therapies
Retrovial: risk of insertional mutagenesis/germline integration
Adenoviral: low risk of insertional mutagenesis; severe immune response
Non-Viral: safest; no integration
Duration of Gene Therapy Approaches:
Retroviral: integrate –> passed to daughters
Adenovital: short lived–> not passed to daughters
Non-Vital: short lived -> not passed to daughters
Chromosomal Analysis Uses
aneuploidies chromosome deltions duplications insertions of moderate to large (3kb to 5kb) rearrangements
Chromosomal Analysis cannot diagnose..
single gene deletions
point mutations
small deletions, duplications, insertions, methylation, TriNT repeats
FISH can diagnose
microdeletion syndromes, recognized chromosomal rearrangements in Cancer, gene copy numbers, anueploidies in pernatal setting
Fish Cannot diagnose
deletions, rearranements that were not specifically tested for
Canot detect duplications
Expression array
tests the RNA expression of genes
tests the activity of genes rather than just the presence or absence of a gene or gene variant
Chromosomal Microarray Can diagnose
small genomic deletions/insertions >200 for deletions and >400 for duplications
aneuploidies, unbalanced chromosome rearrangements
CMA cannot diagnose
deletions and duplications below resolution of MCA, NT mutations, balanced chromosomal rearrangements
DNA sequencing can diagnose
Mutation in known genes, polymorphic variants, small 1-100 NT deletion/insertions,
ideal for looking at the sequence of a known disease gene
DNA sequencing cannot diagnose
regions that are not being tested, regions of the gene (promoters, introns) that arent sequenced,
extremely large deletions or insertions, rearrangements, chromosomal abnormalities
Allelic Heterogeneity
multiple mutations in a particular gene of loci can cause disease
Genetic Heterogeneity
multiple genes when mutated are associated with same phenotype.
Alpha Globin
Ch 16 (2 copies per cluster)
Beta - Globin
Ch 11 (1 copy per cluster)
Alpha cluster
zeta-alpha2-alpha1
beta cluster
epsilon - gammaG-gammaA-delta-beta
Pseudogene
resembles a gene but makes no protein
