HC6 Flashcards
Spontaneous Mutations
Spontaneous mutations are changes in the DNA that occur naturally without any external factors or exposure to mutagens. They can arise during DNA replication, repair, or recombination processes. Errors relatively common, but in most cases error is detected and repaired by enzymes in nucleus. Errors that go undetected and un-repaired have potential to change phenotype.
Chromosomal Abnormalities
Damaged, broken, missing, or extra copies of (part of)
chromosomes
* Translocations of specific chromosomes are more likely to occur (13, 14, 15, 21, 22)
Non-disjunction
Non-disjunction refers to the failure of chromosomes to separate properly during cell division, resulting in an abnormal distribution of chromosomes in the resulting cells. It can occur during meiosis, the process of cell division that produces eggs and sperm, or during mitosis, the process of cell division that produces all other cells in the body.
Only embryonic survivors
a shortage of one chromosome (=monosomic embryo) are those concerning the X-chromosome
a complete extra
chromosome (=trisomic embryo) are those concerning the X or Y chromosome, as well as chromosome 13, 18, 21, 22
Placenta leakage
Fetal (blood) cells escape placental barrier
* Fetal cell-free DNA (apoptosis of placenta) for testing in
maternal blood
Immune response to fetal cells: isoimmunization
Rhesus imcompatibility
Bloods of the mom and fetus do not mix. If Rhesus pos, they have rhesus antigen receptor
if mom is R.neg so no antigen and fetus is R.pos, so anytime the babies blood gets into the mothers blood the mom starts to create antigens.
Single exposure (birth), increased potency to attack the second Rh+ child
Amniotic Fluid Embolism
a rare and potentially life-threatening complication of pregnancy. It occurs when amniotic fluid, fetal cells, hair, or other debris enters the maternal circulation, leading to a sudden onset of hypoxia, hypotension, and severe coagulopathy.
Amniotic fluid embolism symptoms
coughing, difficulty breathing, resulting tachycardia and lapses of oxygen saturation, followed by hypotension and cardiovascular collapse with severe respitatory problems
Growth restrictions
Disruption= knots in umbilical cord; too long=hypoxia
Amniotic banding
Deformation; mechanical forces; clubfeet
Dizygotic twins
fraternal twins= develop when 2 separate oocytes were ovulated and subsequently fertilized (each by one sperm)
Not identical genetics
60-70% of twins 1 in 100 births
Heritable (relates to higher levels of FSH and folliculogenesis)
Monozygotic twins
Identical twins, genetic makeup is identical because they are formed from same pair of gametes
-result stage ranging from: separation of blastomeres early/late in cleavage
-splitting of inner cell mass before gastrulation
When can splitting occur
at two cell stage
at splitting in early blastocyst yealds two inner cell masses
later splitting yiealds two embryos from one inner cell mass
Hydatidiform moles
Placenta forms cysts (hollow
structures); chorionic villi contain
water:
* Complete: all villi
* Incomplete: some vill
* Complete: No fetus formed;
hCG present (high levels)
* Incomplete: Finally no viable
fetus at birth; fetus very
malformed (not always visible)
* Painless vaginal bleeding in the
fourth to fifth month of pregnancy
Complete hydatidiform mole
An oocyte is inseminated by two sperm and female pronuclei is lost or two male pronuclei combine to form diploid nucleus
Dispermic fertilisation
(46, XX or 46, XY)
Monospermic fertilization
loss of maternal pronuclei (46, YY cannot develop)
Partial hydatidiform moles
An oocyte is inseminated by two sperm (or an abnormal diploid sperm)
Female pronucleus and two male pronuclei combine to form triploid nucleus (69, XXX, 69, XXY, 69,XYY)
Morphogens
signaling molecules that play a crucial role in the development of tissues and organs in organisms. They act as positional cues, providing spatial information to cells and controlling cell fate and tissue growth. Morphogens are produced by specific cells and form concentration gradients, with different concentrations of the morphogen signaling different cell responses. The distribution of morphogens is regulated by various mechanisms, including diffusion, binding to extracellular molecules, and transport on lipid-containing carriers.
exquisite balance
All morphogens that determine axis formation, outgrowth of
tissue or apoptosis should be present in a exquisite balance
(e.g. the gradient as present in the brain-to-be: neural tube
SHH mutations
SHH mutations affect the midline
SHH & Gli3 mutations results in
polydactyly;
Hox gene mutations in syndactyly
Absence of FGF8 could cause split
foot anomaly
total deletion of Shh and/or Six3b results in no midline structures formed (lethal)
RA is important for
anterior-posterior axis formatio
X-chromosome inactivation
- Every individual lives with
one active X-chromosome
(m/f) - Females are genetic
mosaics due to random X-
chromosome inactivation - Blastocyst stage (embryo
has 5000 cells) - X-linked diseases:
phenotype in females
depends on which
chromosome is inactivated
and what the cells
contribute to - Males just have a single X-
chromosome
random
True mosaicism
True mosaicism refers to
cells where 1 chromosome
is lost
* Non-disjunction in early mitotic
divisions of one of the
blastomere
* Turner syndrome / trisomy 18
or 21
* The later non-disjunction
happens in the zygote, the
fewer the contribution of the
mosaic genotype
* Phenotype depends what
cells harbor the missing
chromosome
Xist Locus
Xist (X-inactive specific transcript) is a long non-coding RNA (lncRNA) located on the X chromosome.
It is only expressed on the X chromosome that will be inactivated (Xi).
The Xist gene produces RNA that spreads across the chromosome, initiating its silencing.
Xist RNA physically spreads over the X chromosome from which it is transcribed.
This coating recruits repressive chromatin modifiers that shut down gene expression.
CpG islands are regions in DNA with a high frequency of Cytosine-Guanine (CpG) sites, often found in gene promoters.
DNA methylation (addition of -CH₃ groups to cytosines in CpG sites) is a key mechanism of gene silencing.
Methylation prevents transcription factors from binding, keeping the inactive X chromosome (Xi) silen
