Exam 5: Genetics of Development - Birth Defects

Question 1

5 cellular processes that constitute development

Answer 1

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

Question 2

apoptosis

Answer 2

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

Question 3

apoptosis in development of immune system

Answer 3

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

Question 4

cell migration in development of CNS

Answer 4

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

Question 5

congenital adrenal hyperplasia

Answer 5

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

Question 6

developmental fate

Answer 6

cell travels down a developmental pathway toward final fate

loses potential to become anything along way

Question 7

general transcription factors

Answer 7

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

Question 8

hermaphroditism

Answer 8

person has both testes and ovarian tissue

very rare

Question 9

HOX family of transcription factors

Answer 9

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

Question 10

lissencephaly

Answer 10

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

Question 11

LIS1 gene

Answer 11

gene required for ordered pattern of migration

mutation causes lissencephaly (smooth brain)

Question 12

morphogen

Answer 12

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

Question 13

polarizing secretion

Answer 13

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

Question 14

polycystic kidney disease

Answer 14

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

Question 15

polycystin

Answer 15

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)

Question 16

pseudohermaphroditism

Answer 16

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

Question 17

role of cholesterol in development

Answer 17

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

Question 18

Sex-determining Region of Y (SRY)

Answer 18

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

Question 19

Smith-Lemli-Optiz syndrome

Answer 19

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

Question 20

Sonic Hedgehog protein (Shh)

Answer 20

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

Question 21

Specific transcription factors

Answer 21

only function in specific cells and at a specific time

like HOX transcription factors

Question 22

statins

Answer 22

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

Question 23

Testes Determining Factor (TDF)

Answer 23

located in SRY

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

Question 24

transcriptional regulatory modules

Answer 24

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

Question 25

tumor progenitor cell model

Answer 25

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