Genetics Objectives 23
1.
Pluripotent: a cell that is capable of giving rise to multiple structures (stem cells
that can give rise to erythrocytes, leukocytes, platelets, etc.)
Differentiation: maturation of a cell line from pluripotency to its ultimate
determination (stem cell determination)
Specification: pluripotent cell growth into a specific cell type when grown
autonomously; different from differentiation because cell may change to a new
cell type if transplanted into a new part of the embryo
Housekeeping genes: 80-90% of human genes, genes that are expressed for
fundamental and universal cellular processes (genes responsible for RNA
synthesis, protein synthesis, cellular division, etc.)
Specialty genes: 10-20% of human genes, genes that direct unique functions of a
cell line (genes responsible for gene regulation such as transcription factors
binding to promoters, silencers, or enhancers)
Epigenetic: changes in genetic expression without DNA sequence change (skin
fibroblasts and osteoblasts have the same genetic sequence, but obviously differ in
their gene expression)
Paracrine signals: a protein with a short-range effect providing a simple on/off
switch (dihydrotestosterone in external genitalia masculinization)
Morphogens: a signal that has a variable effect, usually in limb development.
They are important in determining cells along the anterior-posterior axis,
proximal-distal axis, and dorsal-ventral axis (WNT and SHH signaling in limb
development)
2.
Tyrosine kinase receptor structure:
Signaling process from extracellular to intracellular: ligand binding,
dimerization, cytosolic domain unfolding, tyrosine kinase activation,
autophosphorylation, initiation of signal cascade
3.
Functions and disorders of:
a.
HOX genes: produce a 60 amino acid “homeobox” that binds DNA and
induces cell division and differentiation to produce distinct body
segments. HOXA and HOXB families control the central axis while
HOXC and HOXD regulate the limbs. A disorder in HOXD13 causes
webbing of the interphalangeal spaces and extra digits (syndactyly and
polydactyly)
b.
PAX genes: produce a 128 amino acid “paired box” that binds DNA and
induces cell differentiation. Type I and type III Waardenburg syndrome
are characterized by abnormal neural crest cells and migrations, and are
caused by mutations in the PAX3 gene.
c.
FGFR genes: produce tyrosine kinase receptors that are stimulated in the
fibroblasts of cartilage and bone. See question #5 for disorders.
4.
Cell-autonomous signals: differentiation signals caused by internal gene
products (PAX3, HOXD13, and FGFR3 mutations)
Cell-nonautonomous signals: differentiation signals caused by external gene
products (DHT in masculinization, WNT and SHH gene products in limb
development)
5.
Allelic: diseases that are caused by a mutation in the same gene
Disorders from mutations in FGFR3: caused by mutations that increase the
function of FGFR3
a.
Achondroplasia: shortening of the proximal extremities, enlarged cranial
vault, and short fingers
b.
Hypochondroplasia: a milder version of achondroplasia
c.
Thanatophoric dysplasia: uniformly lethal condition with a generalized
shrinking of bone, and thus, a narrow chest cavity causing respiratory
insufficiency