Chapter 24: Development in Health and Disease Flashcards
3 main mechanisms of defect
1) stochastic effects: random chance events
2) genetic: gene mutations of alterations in the number of chromosomes
3) environmental: outside chemical/agents that affect phenotype by either inhibiting or enhancing developmental signals.
Protein syntehsis is:
stochastic. there are random fluctuations in transcription and translation, affecting the amount of transcription, paracring factors, receptors, etc. Leads to variations in the levels of proteins produced at any given time.
- this results in the random activation or inhibition of cellular pathways in a random manner.
example of a stochastic event
X chromosome inactivation in females.
- Xchromosomes carries alleles for clotting factor.
- someone may not carry 2 normal copies of clotting factor; they may be heterozygous for a mutant copy of clotting factor
- there is a random chance of X activation– if the wildtype X chromosome is activated, the person will be normal. If the mutant X chromosome is activated (WT X is inactivated) by chance), hemophelia will arise.
2 main genetic errors of human development
1) aneuploidies
2) pleiotrophy
aneuploidy
errors in development caused by improper number of chromsomes, or chromosomal translocation
pleiotrophy
a single gene or pair of genes causes multiple effects
2 types of pleiotrophy
1) mosaic pleiotrophy: different effects are generated by genes having important effects in areas of the body.
2) relational pleiotrophy: a defective gene in one part of the embryo causes defects in another part where the gene is NOT expressed.
example of mosaic pleiotrophy
KIT gene is involved in the proliferation of RBCs, pigment cells, germ stem cells. Mutations causes a variety of problems in dif areas of the body thus. such as anemia, albinism, sterility
example of relational pleiotrophy
MITF gene is supposed to be expressed in cells that need pigment. Even in cells that don’t have MITF gene physcially expressed can face complications if there is a mutation in MITF gene. Ex/ MITF gene is not expressed in retinal pigment cells, but it prevents malformation of choroid fissure. If there is a mutation in the MITF gene, there is a loss of vitreous humor which causes the eye to be abnormally small.
example of how aneuoploidies causes mosaic pleiotrophies
trisomy 21 and downsyndrome.
- aneuploidy (extra chromosome) can result in the expression of genes that effect different areas of the body (mosaic pleiotrophies). This extrachromosome (mutation) causes overproduction of regulatory factors involved in controlling development of the heart, muscles, and nerve formation. Causes facial muscle changes, heart and gut abnormalities and cognitive impairment.
in pleiotrophy, the same gene (or genes) causes different effects in different tissues. What is the opposite of this?
genetic heterogeneity: production of similar phenotypes (effects) by mutations of different gene/genes (rather than the same)
example of genetic heterogeneity:
the production of similar effects by mutations in different genes
ex/ the phenotype observed in individuals with KIT mutations (sterility, anemia, albinism) is also caused by mutation of SCF (stem cell factor), which is the paracrine ligand for KIT.
explain how Cyclopia can be an example of genetic heterogeneity
genetic heterogeneity is when multiple genes can cause the same effect. cyclopia can be caused my numerous types of genetic defecits:
1) mutation to SHH gene
2) mutation to genes activated by SHH genes
3) mutations of genes controlling cholesterol synthesis, since cholesterol is needed for proper SHH signalling.
Phenotypic heterogeneity
when the same mutation can produce a different phenotype in different individuals.
how does phenotypic heterogeneity happen? Example?
phenotypic heterogeneity is when the same mutation can produce a different phenotype in different individuals. this occurs because genes do not function independelty, but rather as a network with other genes and proteins.
example. Mutations in the FGFR3 gene can induce mild phenotype abnormalities to lethal malformations depending on the genetic content of the individual.
