Week 2 - Down’s Syndrome Flashcards
What are screening tests?
- tests to identify high risk individuals
- done via ultrasounds, serum markers, NIPT of cff DNA
If an individual is identified as high risk for a baby with DS, what is the next step?
- diagnostic test
- to determine whether or not the baby will have DS
How does ultrasound screening work?
nuchal translucency
- done at weeks 10-14
- an accumulation of fluid at the back of the neck
- risk of DS increases with maternal age and NT length
structural anomalies
- done at weeks 18-21
- shorter limb length
- cardiac defects
- double bubble sign
- can be associated with other conditions
How do serum markers work?
- different types of combined tests to view levels of different proteins
- levels put in an algorithm along with NT measurement and other factors
- if probability is higher than 1:150, then diagnostic test is offered
What types of serum markers tests are there?
- combined test (2 markers)
- quadruple test
- triple test
- quadruple and triple are done when symptoms are presented too late in the pregnancy or the NT could not be measured previously (second trimester)
How does cff DNA work?
- cell-free fetal DNA
- free DNA in maternal blood
- from syncytiotrophoblasts disrupted in placenta
- only present during pregnancy, disappears soon after birth
- detected by DNA sequencing/ PCR/ markers (SNIPS)
- analysed using z-statistic
What are the advantages of cff DNA testing?
- no miscarriage risk
- effective at week 10/11 (early enough to think about termination)
- sensitivity & specificity rate over 99%
How do diagnostic tests work?
- fetal sample is collected
- fetal DNA analysed by karyotyping/ FISH/ QF-PCR
What is a con of collecting fetal cells?
- it is invasive
- causing a risk of miscarriage
What is a robertsonian translocation?
- 2 acrocentric chromosomes fuse together
- chromosome made up of 2 long arms
- no satellites (no genetic material required for development)
How can extra copy of chromosome 21 be turned off?
- XIST: X inactive specific transcript
- XIST RNA coats chromosome
- changes it to heterochromatim
- chromosome compacts/ condenses
- becomes a Barr body
- this is done to silence X chromosome
- same concept for DS
- trisomy 21 induced pluripotent stem (iPS) cell
- injected by XIST and zinc finger nuclease (ZNF)
- ZNF is the mechanism to get a gene into a cell
- Dox inserted to turn on XIST expression
What does aneuploidy mean?
when the number of chromosomes is not an exact multiple of a haploid number
How does Alzheimer’s Disease develop?
- Tau neurofibrillary tangles present in the brain
- Tau is a protein part of the cytoskeleton
- it gets hyperphosphorylated to cause the tangles
What is the hypothesis of the link between DS & Alzheimer’s?
- both consist of having more genes (whole chromosome or a region)
- more genes means more proteins
- more of Amyloid Precursor Protein
- α-secretase usually digests protein
- in Alzheimer’s, β-secretase does not digest the same way forming amyloid plaques
- these are neurotoxic & nonsoluble
- so more of the protein means more plaques and more neurotoxicity
- BUT dementia does not always occur in people with DS, why?
- there must be a protective gene in chromosome 21
- BACE2 is a homolog of β-secretase
- digests some of the protein
- gets rid of the neurotoxic fragment
Why does meiotic non-disjunction rise with maternal age?
- cohesin strength decreases with age, causing premature chromatid separation
- spindle problems, chromosomes are not seperated
- environmental factors
- reduced recombination
- misplaced chiasmata
- telomere shortening, nuclear membrane anchor lost
