Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Cellular and Molecular pathology > 5. Genetics and disease - genetic testing and therapy for genetic disorders > Flashcards

5. Genetics and disease - genetic testing and therapy for genetic disorders Flashcards

1
Q

why do we want to test for genetic disorders?

A

Clinical:
- diagnosis of disorders
- predicting disorders
Population health:
- large cohort patient studies that don’t really benefit the participants but enrich wider knowledge

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what needs to be remembered when interpreting genetic test results?

A
  1. presence of the mutant allele does not always result in disease
  2. there is a limit to test sensitivity and specificity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what is eugenics?

A
  1. a fringe set of beliefs and practices pretending to be science
  2. eugenicists believed in increasing the population frequency of desirable traits and reduce undesirable ones
  3. widely discredited, unethical and scientifically rejected
  4. created by Sir Frances Galton
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what is the legacy of eugenics?

A

the concept of good and bad genes
desirable physical characteristics used in adverts as they sell more

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what is the future of eugenics?

A

unsure as gene editing improves and there needs to be a limit in what we edit
should we edit embyros to prevent disease?

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what techniques are used in prenatal genetic testing?

A
  1. amniocentesis
  2. chorionic villus sample
  3. maternal blood tests
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what indicates a foetus has a genetic disorder?

A

Nuchal translucency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what is Nuchal translucency?

A

an ultrasound that measures the amount of fluid at the back of the neck
lots of fluid = something could be wrong = genetic testing needed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what is amniocentesis?

A
  1. the gold standard of genetic testing
  2. remove some amniotic fluid and grow up the foetal cells
  3. takes a few weeks
  4. done at 16-18 weeks
  5. Only do the test if the other signs indicate a genetic disorder
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

why is amniocentesis done at 16-18 weeks?

A

if it is done earlier then the risk of spontaneous miscarriage is very high.
even at 16 weeks the risk is 1/100

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what is chorionic villus sample?

A
  1. remove part of the chorionic villus which is part of the placenta
  2. less invasive the amniocentesis
  3. done at 11-12 weeks
  4. get sufficient tissue for immediate analysis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what is the maternal blood test?

A
  1. detect cell-free foetal DNA in maternal blood
  2. can detect trisomies
  3. least accurate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what is neonatal genetic testing done for?

A
  1. for diagnosis and screening done via a blood test
  2. phenylketonuria especially which is when they dont metabolise phenylalanine properly but can control with diet
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what is adult genetic testing used for?

A
  1. a choice to get tested
  2. for carrier detection and pre-symptomatic diagnosis for late onset disorders
  3. use of genetic counsellors to help people understand what the results mean
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what molecular Analysis is used to detect defective genes?

A
  1. PCR-based investigations of specific genes looking for deletion and point mutations
  2. indirect determination using allele or locus linkage
  3. NGS sequencing
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

PCR-based investigations of specific genes: deletions

A
  1. look for deleted exons or truncated PCR products
  2. use a specific primer
  3. different PCR products are produced based on the mutation showing up as different bands on a gel
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

PCR-based investigations of specific genes: known point mutations

A
  1. Amplification refractory mutation system (ARMS); make PCR primers for specific mutations
  2. loss/gain of restriction enymes site eg HbS = loss of MstII restriction site
  3. Allele-specific oligonucleotides can be hybridised to PCR products then microarrays
  4. direct sequencing; more common now and the easiest in research environment
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

PCR-based investigations of specific genes: Unknown point mutations

A
  1. screening methods like single-strand conformation polymorphism (SSCP); conformation changes change how the protein runs on the gel
  2. direct sequencing
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

PCR-based investigations of specific genes: PCR by allele-specific genes

A

forward primers = very specific for the sequence
reverse primers = common
if there is a point mutation the primer cannot bind so no PCR product will be observed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

when is indirect determination used?

A
  1. used where the gene is not cloned
  2. relies on genetic linkage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Indirect determination: allele linkage

A

due to the founder effect the polymorphism is always associated with mutation
eg. HbS associated with Heal polymorphism in ß-globin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Indirect determination: locus linkage

A

work out the linkage of a mutant allele to a polymorphic marker in a particular family, normally for prenatal diagnosis but can be unreliable

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Allele linkage and ß thalassaemia haplotype

A
  1. specific set of polymorphisms at different loci on the ß-globin gene cluster inherited as a unit that are associted with developing ß-thalassaemia
  2. due to the founder effect
  3. seven RFLPs in the ß-globin chain cluster from the basis of the ß thalassamia haplotype
  4. specific ß-globin mutations are in strong linkage disequilibrium with specific haplotypes
24
Q

what is a haplotype?

A

a set of polymorphisms that are inherited as a unit

25
Q

Next generation sequencing and genetic testing

A
  1. very high throughput
  2. whole genome or exam sequencing
  3. very good for detecting mutations that we didn’t know about
  4. isolate specific genes to sequence
  5. used for routine detection of known mutations and to pick up previously unknown mutations
  6. includes Sanger and illumina sequencing and nanopore
26
Q

Population genomics: genomics england

A
  1. set up to deliver 100,000 genomes to better understand genetic disease
  2. Sequence 100,000 genomes from NHS patients with rare diseases and common cancers
  3. since 2013
27
Q

Population genomics: UK biobank

A
  1. so far the largest population genome cohort in the world
  2. in-depth genetic and health information from half a million UK participants
  3. since 2006
28
Q

Population genomics: Avon longitudinal study of parents and children

A
  1. bristol based study
  2. birth cohort study
  3. families followed since 1992
29
Q

Population genomics: beyond 1 million genomes study

A

set up to create a network of genetic and clinical data across Europe

30
Q

why is population genomic bias?

A

90% of large genome studies have been in Europe and there is very little data from the rest of the world

31
Q

therapy for genetic disorders

A

conventional treatments like gene product replacement or surgery

32
Q

Treatment of genetic disease: conventional

A

physiotherapy and antibiotics for cystic fibrosis

33
Q

Treatment of genetic disease: environmental modification

A

remove/limit the environmental factors that causes the disease like avoidance of sunlight for Xeroderma pigmentosa patients

34
Q

Treatment of genetic disease: surgery

A

correction of virilisation in girls with congenital adrenal hyperplasia to restore hormones to normal levels

35
Q

Treatment of genetic disease: metabolic manipulation

A

changing diet like restricting phenylalanine intake in phenylketonuria

36
Q

Treatment of genetic disease: gene product replacement

A

drugs that replace what the damaged gene is meant to make
eg factor 8 administration for haemophilia A or insulin for diabetes

37
Q

Treatment of genetic disease: targeted drugs

A

eg CFTR correctors that bind to CFTR and try to correct the misfolding
eg Huntington’s disease - antisense oligonucleotides to mRNA

38
Q

Treatment of genetic disease: tissue and organ transplant

A

natural transplants
- heart/lung
- bone marrow
- kidney

Experimental
- neo organs (pig)
- lab grown organs

39
Q

Treatment of genetic disease: pluripotent stem cell therapy

A
  1. can make any cell type
  2. embryonic stem cells so big ethical issues and hard to obtain
  3. induced pluripotent stem cells
    - somatic cells that are induced back into stem cells
    - not quite there yet
40
Q

Treatment of genetic disease: multipotent stem cell therapy

A

can make many cell types
eg mesenchymal stem cells

41
Q

Gene therapy

A
  1. correct defected gene with a synthetic transgene or by introducing a correcting gene product
  2. gene replacement by targeted homologous recombination is theoretically possible
  3. gene editing (CRISPR-Cas9) now being used to replace defective genes
  4. most strategies include leaving the defective gene in place
42
Q

in vivo gene therapy

A

transgene introduce directly into the body

43
Q

ex vivo gene therapy

A

Transgene introduced into cells in a laboratory then transplanted back

44
Q

germline gene therapy

A

correct the defect in gametes or embryos so all the cells are corrected.
complicated and ethically ambiguous

45
Q

somatic gene therapy

A

target defective cells or organs

46
Q

ex vivo gene therapy process

A
  1. take a cell sample
  2. culture in lab
  3. introduce transgenes
  4. select for the new gene
  5. return cells to the patient
47
Q

what needs to be considered with gene therapy?

A

not all genes are expressed in all tissues so needs to be kept localised
eg the eyes would be a good target as they are quite isolated

48
Q

Gene therapy vehicles: viral vectors

A
  1. retroviruses, adenoviruses, lentiviruses
  2. effecient as it is what they have evolved to do
  3. safety problems as you don’t want to give the patient a viral infection
  4. must be replication deficient
  5. insertional mutagenesis
49
Q

Gene therapy vehicles: physical methods

A
  1. liposomes - like mini cells
  2. receptor mediated endocytosis
  3. direct DNA injection
  4. inefficient compared to viral vectors
  5. safe
50
Q

problems with gene therapy vehicles

A

producing and sustaining high level transgene expression

51
Q

Gene therapy targets: bone marrow

A
  1. haemoglobinopathies and other defects
  2. need to get to the stem cells
  3. bone marrow transplants for ex vivo work but extraction is painful
52
Q

Gene therapy targets: liver

A
  1. for metabolic defects
  2. the liver can regenerate so will it do it right?
  3. is ex vivo possible?
53
Q

Gene therapy targets: muscle cells

A
  1. for muscular dystrophy
  2. can use direct injection of DNA into muscles
54
Q

Gene therapy targets: lung cells

A
  1. cystic fibrosis treatment in vivo
  2. easy to get drugs into the lungs due to inhalation
  3. viral and physical vectors
  4. not been hugely successful so far
55
Q

treatment of cystic fibrosis

A
  1. very large gene so hard to correct
  2. conventional therapy includes physiotherapy, bronchodilators and antibiotics
  3. corrector/ potentiator combination therapy to restore CFTR function
56
Q

corrector/ potentiator combination therapy to restore CFTR function in cystic fibrosis

A
  1. been used for a few years
  2. can really improve quality of life but lung function only improves 20% max
  3. corrector target protein misfolding mechanisms by binding to different sites on the defect protein to get it to refold
  4. increases cell surface expression of CFTR
  5. potentiator helps move Cl- through the proteins

Cellular and Molecular pathology (25 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions