Exam 5: Genetics of Development - Birth Defects Flashcards Preview

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Flashcards in Exam 5: Genetics of Development - Birth Defects Deck (25):

5 cellular processes that constitute development

Transcriptional regulation
Morphogen and cell to cell signaling
Changes in cell shape and organization
Cell migration
Programmed cell death



programmed cell death
required for development of heart, immune system, connection between uterus and vagina, separation of individual digits, perforation of anal and choanal membranes


apoptosis in development of immune system

lymphocyte lineages that react to self-components are destroyed by apoptosis
failure to destroy them leads to autoimmune diseases


cell migration in development of CNS

neuronal stem cells on ventricular side of neural tube divide and create neuronal precursor cells - migrate outward from ventricle along scaffold of glial cells
Each wave passes through layers of precursor cells - outside the last created, closer to core are oldest cells


congenital adrenal hyperplasia

causes female pseudohermaphrodites - normal ovaries but ambiguous or male genitalia
caused by defect in a 21-hyroxylase involved in cortisol biosynthesis - blocks cortisol synthesis causing intermediates to be sent to androgen synthesis pathway
females have high levels o androgens and develop ambiguous or male genitalia


developmental fate

cell travels down a developmental pathway toward final fate
loses potential to become anything along way


general transcription factors

unspecific transcription factors - regulate gene expression (activate or repress)
found in thousands of transcriptional complexes



person has both testes and ovarian tissue
very rare


HOX family of transcription factors

patterning along anterior-posterior axis
HOX genes 11 & 13 involved in development of distal pole of limbs
Mutations in HOXA13 and HOXD13 disturb development of fingers and toes



mutation or deletion of LIS1 gene interfers with migration
cerebral cortex is thickened and lacks defined cell layers - appears smooth
severe mental retardation


LIS1 gene

gene required for ordered pattern of migration
mutation causes lissencephaly (smooth brain)



diffusible factors secreted by cells in one part of embryo
diffuse through tissue and signal position based on gradient
cells initiate certain developmental program/pattern based on morphogen concentration in environment


polarizing secretion

occurs during development - cell responds to environmental clues
polarizes secretion of proteins to apical or basal surface of cells


polycystic kidney disease

develop kidney cysts - can be seen as an overgrowth of a kidney duct caused by failure of epithelial cells to stop dividing
mutations in polycystin 1 & 2 genes cause kidney cells to fail to sense fluid flow = cell proliferation continues and development of polarity does not occur



genes in kidney epithelial cells
mutations to these genes prevents cell from sensing fluid flow and lead to development of kidney cysts (polycystic kidney disease)



have either testes or ovarian tissues, but patient's phenotype does not represent genetic sex


role of cholesterol in development

disturbances in cholesterol synthesis have broad impact on development - Shh protein must interact with cholesterol
exposure of fetus to cholesterol-lowering drugs (statins) cause birth defects (shortage of cholesterol for Shh function)
defect in cholesterol biosynthesis causes SLOS - impairment in Shh signaling caused by cholesterol defects - leads to severe congenital malformations


Sex-determining Region of Y (SRY)

critical region on Y-chromosome for male development
gene for Testes Determining Factor (TDF) located here - initiates testes development
if SRY deleted on Y chromsome embryo develops into female with XY karyotype
If SRY is translocated to X-chromosome, embryo develops into male with XX karyotype


Smith-Lemli-Optiz syndrome

autosomal recessive disorder (rare)
severe congenital malformations
caused by defect in cholesterol biosynthesis - insufficient cholesterol concentrations impair Shh function


Sonic Hedgehog protein (Shh)

developmental morphogen secreted from notochord and floorplate of developing neural tube
gradient helps organizing cells in brain and spinal cord
mutations in signaling lead to midline defects
also secreted from zone of developing limb to induce development of posterior limb elements


Specific transcription factors

only function in specific cells and at a specific time
like HOX transcription factors



cholesterol lowering drugs
when exposed to fetus in utero causes birth defects
inhibition of cholesterol synthesis leads to shortage of cholesterol for Shh functioning = SLOS symptoms like birth defects


Testes Determining Factor (TDF)

located in SRY
initiates development of testes, which secrete androgen and initiate synthesis of male external genitalia


transcriptional regulatory modules

groups of transcription factors expressed together for same purpose
regulate gene expression, can be activators or repressors


tumor progenitor cell model

Predicts errors in epigenetic programming of stem cells during development lay seed for cancer later in life
abnormalities in epigenetic programming of stem cells create pool of incompletely differentiated cells - retain some embryonal potential and can grow into benign tumor
Additional mutations lead to malignant transformation