Student seminar 9/9- DS Flashcards
Down Syndrome Def
a genetic disorder caused by abnormal cellular division
Down Syndrome Characteristics
cognitive disabilities, metabolic disorders, increased risk cancer
Down Syndrome Types
Trisomy 21, Translocation DS, Mosaic DS
Nondisjunction
abnormal
separation of homologous
chromosomes or sister
chromatids
Trisomy 21
three copies of chromosome 21 causes a disturbance in gene dosage
amyloid-beta-peptide
(formed from APP)
deposits plaques in the brain
APP
Amyloid protein precursor
APP function
precursor to peptides that build up and cause poor cell- to- cell synapses in brain
Direct RUNX1 impact
Down Syndrome and Hematopoietic
Disorders
RUNX1
Transcription factor: controls the activity of target
genes
MYC
oncogene that contributes to the
genesis of many human cancers (regulates
cell function and growth)
RUNX1 affected areas
Development and homeostasis of neural tissue,
heart, muscle, bone, and blood cells
Normal fetal hematopoiesis
High RUNX1 B/C levels
Trisomy 21 + GATA1s mutation
High RUNX1 A levels
—> MYC:MAX—> MYC
Reduced electron flux through
complexes; Results in oxidative stress
too many unstable free radicals and
not enough antioxidants to get rid of
them
Oxidative phosphorylation
– downregulated negatively affected mitochondrial function leads to metabolic issues
Glycolysis (upregulated PFKL gene) & Citric Acid Cycle (upregulated ACLY and OGDH genes)
increased glucose
PFKL
encodes phosphofructokinase
PFK importance to glycolysis
rate-limiting step
Faster glucose metabolism in the brain results in
cognitive disabilities and metabolic disorders (obesity, T2D)
DNA damage from oxidative stress
free radicals can add double bonds and remove an H-atom from the methyl group of thymine
ACLY
encodes for citrate synthase
OGDH
encodes a critical subunit of alpha-ketoglutarate dehydrogenase
Increased production of NADH to carry e- to the electron transport chain (Citric Acid Cycle)
weakened mitochondrial content results in e- escaping across the membrane
Electrons are captured by O2 creating free radicals (citric acid cycle)
cause protein and DNA damage
= morphological abnormalities, immune disorders, premature aging
DS mRNA and protein levels(figure)
mRNA levels were found to be upregulated
protein levels were downregulated
post translation things going on after the mRNA is made into protein (high mRNA low protein
NADH FADH2 roles in mitochondria
formed in glycolysis, fatty acid oxidation, and the citric acid cycle are used to reduce oxygen to water by a series of electron carriers located in the inner mitochondrial membrane.When the inner membrane becomes weaker and less stable due to the affected mitocondria
