L5 - Genetic testing and therapy for genetic disorders Flashcards
ethical considerations of genetic testing
slinical vs population health
legal,sovial and mental health
what are eugenics
set of beliefs and practices that believe in ibcreasinging population frequency of ‘desireble traits’
= very unethical
= ‘good’ and ‘bad’ genes is widely forwned against
3 forms of pre-natal testing for down syndrome/monogenic defects
Aminocentisis
choronioic villus sample
NIPT
describe aminocentsisis
pre-natal diagnostic test
obtain and grow foetal skin cells from amniotic fluid
= undergo genomic analysis including karyotyping –> directly look at the foetus’s chromosomes to detect any abnormalities.
when do you do aminocentsisi
16-18 weeks gestation
describe CVS - Choronioic villus sample
pre-natal diagnostic test -
takes cells from chorionic villi via a needle through the abdomen
= undergo genomic analysis including karyotyping –> directly look at the foetus’s chromosomes to detect any abnormalities.
if you get suffiecient tissue you can do immediate analysis –> Aminocentsis requires growing of cells
what do diagnostic tests likeCVS and aminocentissi use to obtain samples
needle guided by ultrasound probe
= invasive so come with risk
what is NIPT
Non-invasive prental testing
= uses cell-free DNA from the baby in the mother’s blood and next-generation sequencing to analyse DNA fragments
= new and very impressive technique
when is CVS undertaken
11-12 weeks
describe the combined test
offered between 10-14 weeks
includes a blood sample taken from the arm and an ultrasound measuring the thickness of the ‘nuchal translucency’ at the back of the baby’s neck
= blood test measures biochemical markers (hCG and PAPP-A)
= placenta develops from the same fertilised egg as the foetus, so it contains the same genetic makeup
how large is the thickness of the nuchal transluency at the back of the babies neck to be linkied with anneuploidy
3mm
what are neonatal and adult genetic tests
Neonatal: tests on newborns
–> screen for mtebaolic disorders
Adult testing: any point in aapersons life
–> screen for late onsery disorders
what are the 2 main groups of testing for disorders
chromosome analysis:
standard methods > karyotyping, FISH
molecular analysis:
PCR-based investigation of spcific genes
DNA sequencing
how can we use PCR to investigate specifc genes in molecular analysis
for known mutations:
make primers specifc to mutations = if mutation present this gene is amplfified and can be detected
loss or gain of restriction site –> partial digest with known RE
microarrays to analyse RNA in cell/gene expression with gene-specifc oglioncueltides to hybrise to PCR product
Sequencing = can be used to idnetufy known and unknown mutations
describe next gen sequencing
nanopore or illuminate- sanger is a classical and slower method
= whole genome or exon sequencing = can detect any mutations by comparrison to database
explain indirect determination as a form of olecular analysis
instead of trying to find a gene/mutation directly
= looks for another marker that the mutation may be there
= gene expression or prescence of polymorphic marker due to linkage
describe a conventioanl therapy for cystic fibrosis
antibiotics to remove thick mucous
what is a environmental modification treatment for Xeroderman pigmentosa
avoid sunlight
= UV sensitivity causing pyrimdine dimers
give an exmaple of a gene product replacemnet treatment
insulin for diabetes
= giving gene product they cant amke themselves
whatr are IPS
induced pluripotent stem cells
=can differentauet into nealry any cell type
name 2 types of gene therapy
Gene editing by CRISPR-cas = replace defective genes pr inactiavte
gene replacement by targetted HR –> theoretically possible but very difficult
2 ways to adminsiter gene therapy
ex vivo:
cells isolated and modified before being returned to patient
in vivo:
the gene is directly adminstered/inserted into the cells via a ‘veichle’ inside the body
=
what are the 2 types of vehicles used for in vivo gene therapy
Tools used to deliver the new gene into the cells
- Viral vectors:
Modified viruses like retrovirsues that infect and insert new gene into genome - Physical method:
liposomes/fat bubbles used to del;iver DNA to cell
describe limitations of viral and physical methods as vehicles for in vivo gene therapy
viral:
virus must be changed so it can’t reproduce in the body.
It can accidentally insert the gene in the wrong place in the DNA
physical:
safer but less effective
