Aneuploidy Flashcards
what genetic abnormality is the most common genetic cause of developmental and intellectual disability, and fetal loss in the first trimester?
aneuploidy
most common mechanism of aneuploidy is meiotic nondisjunction
and nondisjunction in these diseases is usually caused by maternal nondisjunction in meiosis II, due to halt in cell cycle during oocyte development
how can you determine whether nondisjunction occurred during meiosis I or II?
look at polymorphisms around the centromere, because that region suppresses crossover
this gives accurate idea of where the chromosome came from (identify chromosome by its centromere)
when in meiosis does crossover occur?
prophase I
if nondisjunction occurred during meiosis I, what chromosomes would the daughter cells have?
one daughter cell would have both homologous chromosomes (pretend one red, one blue).
In meiosis II, these will split so each daughter cell has a chromatid from each of the homologous chromosomes (so one blue stick and one red stick in each cell, instead of just one).
second daughter cells has neither, so in meiosis II there is nothing either
if nondisjunction occurred during meiosis II, what chromosomes would you expect the daughter cells to have?
a daughter cell from meiosis I with one homologous chromosome (tetrad - remember chromosomes are counted by how many centromeres there are) would split the two chromatids, but both would end up in only one daughter cell
what banding pattern might you see if you ran the DNA of the four daughter cells of meiosis, if nondisjunction in meiosis I had occurred?
what pattern would you see if nondisjunction occur during meiosis II?
(describe the banding pattern only for the nondisjunction)
meiosis I nondisjunction: 2 daughter cells would have 2 bands (the same bands), the other 2 would have none
meiosis II: 1 daughter cell would have a thick band for 2 copies of the same chromosome, 1 daughter cell would have no bands, and the other 2 daughter cells would have just 1 normal band
what is the most common cause of uniparental disomy
trisomic rescue - body tries to compensate by removing the extra chromosome, but depending which is removed, uniparental disomy can occur (if it did not remove one of the repeats)
how can a recessive disease occur in a patient of which only one parent is a carrier?
uniparental disomy - they get 2 copies of the mutant allele
what its the most common chromosomal abnormality, and most frequent genetic cause of cognitive disability?
Trisomy 21 - Down Syndrome
You’re shadowing in L&D when you see a neonate, born to a 45yo F, being delivered in 39th week of gestation. The neonate has a flattened face, epicanthal folds, and echocardiography reveals endocardia cushion defect. What condition does this child likely have?
Down Syndrome (Trisomy 21), due to meiotic non-disjunction
most common chromosomal abnormality and most frequent cause of cognitive disability
what are the key clinical features of Trisomy 21 for:
1. Head and neck
2. Neurological
3. Heart
4. GI
head and neck: slanted palpebral fissures (slanted eyes), flat facial profile, low set ears, macroglossia (protruding tongue), nuchal folds (back of neck), brachycephaly (wide head)
neuro: early-onset Alzheimer’s, hypotonia, cog. disability
heart: ventricular or atrial septal defects (due to defect in fusion of tissues that make endocardia cushions)
GI: duodenal atresia (lumen is not open), Hirschsprung’s disease
also at high risk of neoplasias (leukemias)
D - duodenal atresia
O - opening in heart due to septal defect
W - loW cog. function
N - neoplasia, nuchal folds, non-disjunction
neonate presents with nuchal folds, macroglossia, and brachycephaly. heart examination reveals an atrial septal defect, and GI examination reveals duodenal atresia. What is your diagnosis, and what important disorders are they at high risk for?
Trisomy 21 (Down syndrome)
at high risk for early-onset Alzheimer’s and neoplasias (leukemias)
this second-most common chromosomal abnormality presents with rocker-bottom feet, clenched hands, a prominent occiput, and dolichocephaly. What is?
trisomy 18: Edward Syndrome
severe cognitive disability
[dolichocephaly = long head]
what are the key clinical features of Edward syndrome?
aka Trisomy 18
key features:
- prominent occiput
- rocker-bottom feet
what is Patau syndrome and how does it present?
aka Trisomy 13
features:
- anophthalmia (missing an eye)
- cleft lip or palate
- Holoprosencephaly (prosencephalon/ forebrain misdevelops)
- polydactyly (extra digits)
