Human Genetics Flashcards
0
Q
Limitations of cytogenetics
A
- only large abnormalities seen
- labour intensive
- specially trained staff
1
Q
Reasons for cytogenetics referral
A
Infertility
Recurrent miscarriage
Primary and secondary amenorrhea
Amniotic fluid for advanced maternal age
2
Q
4 main samples used in cytogenetics
A
- blood
- amniotic fluid
- chorionic villus
- bone marrow
3
Q
3steps in the sample processing
A
- culture
- harvest
- analysis
4
Q
What is used to arrest cells in metaphase?
A
Colcemid
5
Q
What does the potassium chloride do?
A
Hypotonic, so cells swell
6
Q
Name 6 main types of structural chromosome abnormalities
A
- deletion
- ring chromosome
- duplication
- isochromosome
- inversion
- translocation
7
Q
Two types of deletion
A
- terminal
- interstitial
8
Q
Types of staining
A
- Giemsa banding
- reverse banding
- telomeric banding
- centromere banding
- NOR banding
- quinacrine banding
9
Q
4 things needed to name a band
A
- chromosome number
- arm symbol
- region number
- band number within that region
10
Q
Use of FISH
A
- microdeletions/duplications
- aneuploidy
- haematological disorders
11
Q
Why is FISH useful for blood samples?
A
- rapid, specific and accurate
- not necessary to have good metaphases
- able to combine several techniques and detect different nucleic acid targets in the same preparation
- greater number of signals can be counted
12
Q
Advantages of using FISH for haematological disorders
A
- can detect a number of translocations
- can be used to monitor minimal residual disease after treatment
- can detect gene amplifications associated with an adverse prognosis for certain tumours
- can be used to confirm engraftment
13
Q
Describe a dual-fusion assay
A
- utilizes large probes that span 2 break points
- optimal for detection of low levels of nuclei possessing a simple balanced translocation
- greatly reduces the number of normal background nuclei with an abnormal signal pattern
14
Q
Describe break-apart assays
A
- useful in the evaluation of genes known to have multiple translocation partners
- differently coloured probes hybridize to targets on opposite sides of the breakpoint of the affected gene
15
Q
Definition of monogenic disease
A
Diseases that result from modifications in a single gene occurring in all cells of the body
16
Q
What may influence pedigrees in monogenic disorders?
A
- reduced penetrance
- variable expression
- anticipation
17
Q
Define reduced penetrance
A
When a person carrying a gene mutation manifests no signs
- AD ectrodactyly
18
Q
Define variable expression
A
The way in which the disorder manifests differs between affected individuals
- tibial aplasia
19
Q
Define anticipation
A
Presentation worsens with successive generations
20
Q
What does MECP2 do?
A
It is a multifunctional epi genetic modulator
- binds to forms of DNA that have been methylated
- condenses the chromatin structure and form a complex with histone deacetylase or directly block TFs
- May function as a transcriptional activator
- highest levels of expression in neurons
21
Q
What type of inheritance is Rett syndrome?
A
X linked dominant
22
Q
Stages of female Rett syndrome
A
- normal period
- sudden decrease in interaction and slowing of progress
- rapid developmental regression
- deterioration slows, hand stereotypies, more interaction
- loss of ambulation, spasticity
23
Q
Features of PPMX syndrome
A
- severe ID and psychosis
- parkinsonian features
- pyramidal signs
- macro-orchidism
24
Features of MECP2 duplication syndrome
- hypotonia
- severe ID
- epilepsy
25
How to explain Rett syndrome
- X inactivation pattern
- depends on type of mutation (nonsense worse than missense)
- depends of site of mutation
- other genes can also be responsible
26
Possible functional modifiers in Rett syndrome
- alterations in the dopaminergic system
- oxidative stress burden
- mitochondrial dysfunction
27
Types of microarrays
- DNA
- protein
- tissue
- cellular
- chemical compound
- antibody
- carbohydrate
28
Types of DNA arrays
- expression chips
- array CGH (comparative genomic hybridization)
- mutation/ genotyping microarrays
29
Features of stargardt macular degeneration
- autosomal recessive
- juvenile onset
- mutations in ABCA4 gene
30
Pros and cons of ABCR400 microarray
- molecular diagnosis is unequivocal
- raw microarray data cannot be delivered to patients without verification
- chips only detect mutations at known points
31
Definition of an adverse effect
Undesired events causing harm to patients, not by the underlying disease, but as a consequence of examination, treatment or care
32
Definition of pharmacogenetics
The study of the role of inheritance in individual variation in response to xenobiotics
33
Role enzymes in metabolizing drugs
- modify most of the chemicals to which humans are exposed
- convert them into more readily water-sol metabolites to be removed from the body
- some reactions lead to formation of highly reactive intermediates
34
What can genetic polymorphism lead to
- abolished enzyme activity
- reduced enzyme activity
- increased enzyme activity
- no change
35
Aspects of pharmacokinetics
- absorption
- distribution
- metabolism
- excretion
36
Aspects of pharmacodynamics
- receptors
- ion channels
- enzymes
- immune system
37
Problems with poor metabolizers
- too slow drug metabolism
- too high drug conc at standard dose
- high risk for adverse reactions
- no response from pro drugs
38
Problems with ultra metabolizers
- too rapid drug metabolism
| - no drug response at standard dose
39
At what levels can genetic variation occur?
- chromosomal
- DNA sequence
- nucleotide
40
What is a haplotype?
A combination of alleles at adjacent locations on a chromosome that are inherited together
41
Types of mutations
- missense
- synonymous
- nonsense
- sense
- frame shift
- mutation affecting polyA
- splice site mutation
- unstable mutations
42
Factors affecting a pedigree
- disease may not have shown phenotypically or person deceased prior to onset
- spontaneous mutations
- family size (small shows fewer)
- variable gene expression
- protective effect on mutation carrier
43
Define detoxification
Conversion of lipid soluble chemicals into water soluble metabolites
44
Define metabolic activation
Converting inert compounds into highly reactive molecules
45
What is special about CYP?
- single CYP can metabolize many compounds
- many CYPs metabolize same compound at different sites
- many CYPs metabolism same compound at same site at different rates
46
Factors influencing drug metabolism
- age
- lifestyle
- genetic polymorphisms
- health status
47
Definition of genetic polymorphism
The recurrence within a population of 2 or more genetic variants of a specific trait in such proportions that they cannot be maintained by simple mutation
48
How are effects of polymorphisms measured?
- phenotypically
| - metabolic ratios
49
Possible effects of polymorphisms
- increased enzyme induction
- altered enzyme activity
- altered enzyme stability
- altered enzyme specificity
50
Genetic determinants of HIV progression
- genetic diversity of HIV
- host genetic susceptibility
- host pharmacogenetics
51
Why is pharmacogenetics considered in HIV?
- the prevalence of toxicity
- long term treatment
- complexity of multi drug treatment
52
Possible issues with pharmacogenetics
- takes time to test
- uptake by clinicians
- clinical utility
53
Define xenobiotics
A foreign compound/chemical found in an organism that is not normally produced or expected to be found in that organism
54
Process of using a microarray
- take a sample
- isolate the mRNA
- make DNA copies of mRNA and tag each sample with a different colour
- apply labelled DNA to microarray
- scan microarray
55
What of expression chips do? (Microarray)
Determine the volume at which genes are expressed
56
What do array CGHs do?
Determines genomic gains and losses (copy number variations)
