LMP301 Lecture 18: Prenatal Screening & Neural Tube Defects Flashcards
define: genetics
the science of inheritance
define: Mendelian genetics
single gene (disorders)
define: genomics
science of the genome
define: genome
genetic information specifying an organsim
define: gene
a genetic unit
define: single-copy, translated gene
gene making a protein
define: locus
a genetic location
define: allele
a genetic variant at a locus (wild type vs. mutant)
define: diallelic
2 alleles at a locus
define: chromosome
assembly of genes packed together
define: euploidy
normal number of chromosomes (23 pairs in humans)
define: aneuploidy
- abnormal number of chromosomes
- abnormal content in chromosomes
trisomy 21
genome with 3 copies of chr 21 (Down Syndrome)
how many genomes can 1 person have?
2 (1 from mom and 1 from dad)
besides the 46 chromosomes, what other genomes do we have?
- 100 - 1000 mitochondrial genomes
- organ transplant receivers have 4
- bacterial genomes (millions)
- viral genomes (billions, even more if have flu)
- harmless parasitic genomes
50% of a buccal swab DNA is…
bacterial
where are most parasites in our body found?
GI
How many genomes do transplanted hearts have?
4
define: gene pair
joining of 2 haploids (sperm & egg)
what forms about 4 days after fertilization?
morula
what is the morula?
a solid ball of cells resulting from division of a fertilized ovum, and from which a blastula is formed.
cells begin differentiating process to become embryonic sac, embryo…etc.
size of embryo at 12-15 weeks
dime
when is fetal death the highest?
very early pregnancy; levels off at 20 weeks
why is there substantial rate of embryo loss in very early pregnancy?
- minimizes the possibility of severe malformations
- correct for serious mutations & maldevelopment
- shutdown developmental process early
how is the embryo lost early pregnancy?
- miscarriage
- menstrual loss
the neural tube forms the…
CNS
- brain
- spinal cord
the neural tube forms from the…
ectoderm
what is the incomplete neural tube referred to?
neural groove
what surrounds the neural tube during development?
somite
NTD
neural tube defects
NTD is a family of…
complex congenital malformations
NTD is caused by…
failure of neural tube closure at week 3-4
what does spina bifida lead to?
early death (stillborn) / life-long paralysis
mild form of spina bifida is called…
spina bifida occulta; does not affect nervous system (problems with vertebrate)
how can spina bifida occulta be detected?
x-ray (see defect in lower spine)
anencephaly
neural tube didn’t close at rostral region (near head)
which part of the neural tube may lead to spina bifida?
failure to close at lower spine area
consequences of anencephaly
lethal
- miscarriage
- early stillbirth
- brief livebirth
examples of NTD
- spina bifida (occulta)
- anencephaly
NTD is a ____ disorder
complex
complex disorder
- not due to single gene defect (multiple genes, environment, other factors…)
- complex inheritance patterns
some examples of complex disorders with genetic components
- cancer
- heart disease
- diabetes
- NTD
exposed neural tissue produces…
alpha-fetoprotein
what can increase a-fetoprotein production?
when the neural tissue nerves are exposed to amniotic fluid (more and more a-fetoprotein produced as the embryo develops)
a-fetoprotein can be foun din…
amniotic fluid
- production begins at week 10
- amount peaks at week 12-13
- no AFP found after week 31
amniocentesis
poking syringe in stomach, and drawing out some amniotic fluid for testing
how can NTD be tested for (invasive)
look for AFP by doing amniocentesis
how can NTD be tested for (non-invasive)
AFP crosses to maternal serum via placenta -> maternal serum screen
why is maternal serum screen not the best test to use?
- only get a % risk
- many overlaps and false results
- cannot distinguish between types of NTD
Prenatal screening couples…
NTD screening with screening for trisomy 21
is prenatal screening required?
no, the parent can decide
if screening detects there is something wrong, what is done next?
ultrasound
can we decide what is wrong based on screenings?
no, it is not a diagnosis; further testing must be done
what is used as a diagnosis for NTD?
outpouching (around lower spine/butt), seen from ultrasound
what non-genetic factors affect NTD?
Nutrition & diet
- famine during WWII caused dramatic increase of NTD
what nutrient is used to decrease instances of NTD?
folic acid
what effect does folic acid have on NTD?
- decrease reccurence (if previous baby had NTD)
- prevent (if first baby)
HAS NOT ELIMINATED!
serum folate is transported into the cell by…
hFR & RFC transporter
the folate found inside the cell is called…
5-methyl THF
folate cycling drives…
DNA methylation
5-methyl THF is converted to ___ by ___
methionine
methionine synthase
describe folate cycling (slide 21)
1) 5-methyl THF -> methionine -> SAM
2) SAM adds methyl group on DNA
3) SAM -> SAH -> homocysteine
4) homocysteine -> cystathionine -> cysteine
homocystein is converted by cystathionine by ____
CBS
folate supplements is recommended for…
all women of reproductive age
rates of folate supplement use from 1992 to 2001
slowly increasing, but still less than 50% (bad!)
how is folate supplemented in Canadian diet?
fortified into cereal grains (white flour)
how much additional folate would be provided through fortification of grains?
0.2 mg/day
ARIMA
auto-regressive integrated moving average
Regions in Canada that had the biggest difference after folate fortification (decrease in NTD)
atlantic region (PE, NS, NL)
folate needs another vit to work properly. what is this vit?
vit B12
why is vit B12 needed for folate to work properly?
B12 is used in folate cycling
which enzymes are used in folate cycling?
- MS
- MTHFR
- MTRR
Folate is a __ factor
growth
too much folate may be associated with…
- more rapid growth of colorectal cancers
- shortened survival of cancer patients
(only affect those who already have cancer/predisposition for cancer)
folate may cause cancer?
- decrease chances if you don’t have cancer
- increase cancer aggressiveness if you already have cancer
