Genetics Flashcards
(33 cards)
What are the 3 primary mechanisms of epigenetic regulation?
DNA methylation, post translational modification of histones, regulation by non-coding RNAs
Where are epigenetic regulations most likely to be in use?
ddd
What happens if epigenetic regulations aren’t working properly?
ddd
What is epigenetics?
Transcription or translation modified or influenced without altering genetic sequence, may be inherited in a stable fashion, may be influenced by the environment
What is imprinting?
Parent-of-origin determines whether some genes are expressed or not
The imprinted gene = inactivated gene
Inheritance process independent of classical Mendelian inheritance, and must be able to influence transcription
Epigenetic changes established in the germ line and maintained throughout mitotic divisions
Imprinting is important in neuro development
What is somatic mosaicism?
Somatic mosaicism occurs when the somatic cells of the body are of more than one genotype
What are normal functions of epigenetics?
- Transcriptional control of developmental genes and tissue-specific genes
- Inactivation of X chromosomes in females
- Inactivation of some growth genes according to parent of origin (imprinting)
- Mediation between the genome and the environment (aging, environmental chemicals, learning)
What happens in DNA methylation?
Does not affect matching nucleotides (C-G still works), DOES influence how other entities an bind to DNA
Hypermethylation of CpG island will cause gene to “shut down”, can persist from parental germ line into the zygote
What happens in histone modification?
Histones wind and unwind DNA
Acetylation of lysine residues in the tail of H3 by histone acetyltransferase enzymes can cause: altered electric charge to separate DNA from histones or binding site for chromatin modifying enzymes and basal transcription machinery—> acetylation correlates with the ability to be transcribed
Deacetylation by histone deacetylase condenses chromatin structure, decreases gene transcription
Methylation may allow for binding of a transcriptional repressor protein
What is non-coding RNA?
Functional RNA molecule that is not translated into a protein
Transcribed from DNA, but located in an intron, between genes, or on antisense DNA strand
Translation: tRNA, rRNA, small nucleolar RNA, small nuclear RNA
Gene expression regulation: microRNA, small interfering RNA, piRNA, long noncoding RNA
What is microRNA? What is piRNA?
microRNA:
- Regulates about 60% of human coding genes
- Complementary to mRNA in 3’UTR
- Causes mRNA to decay, reduces gene produce
- miRNA controlled by CpG island methylation
piRNA:
-Transcriptional silencing in spermatogenesis
What is X inactivation? How does it work?
Selective epigenetic inactivation of alleles on one X chromosome
Due to X inactivation, all females are somatic mosaics for X gene activity
Descendants of each cell will have the same X inactivated from that time on
ncRNAs coat X chromosome DNA over very long distances to inactivate
How are females with one abnormal X chromosome affected in disease?
Duchenne muscular dystrophy: female will have normal to slightly elevated creatine kinase activity
Hemophilia A (Factor VIII): female will have normal to 50% Factor VIII
No total loss, just possibility of impaired function. Due to random X inactivation, females affected less than males who only have one X and no X inactivation
How does X inactivation affect women who carry an abnormal gene on one X chromosome?
Extent of phenotype determined by distribution of mosaicism
What are some characteristics of imprintable genes?
- One allele expressed in at least one body tissue
- Occur in clusters
- Alleles inherited through generations will change methylation and activity pattern depending on sex of transmitting parent
- Frequently involves CpG methylation
How are epigenetics disrupted in cancer?
- CpG methylation of tumor suppressor genes
- miRNA expression can act as oncogenes or tumor suppressors, so any changes to miRNAs can lead to lack of tumor suppressing abilities or increase in oncogenes
- piRNA in testicular tumors, snoRNA, lncRNA
How does a lack of miR200 cause cancer?
(1) CpG island hypermethylation of miR200 family
(2) Lack of miR200 transcription
(3) Permits expression of several transcriptional repressors
(4) Allows repression of E-cadherin gene normally responsible for cell-cell adhesion
(5) Permits epithelial-to-mesenchymal transition of cancer and allows cancer to invade
How can miRNAs be targeted for cancer therapy?
- If miRNA overexpression is causing cancer, inhibit miRNA function
- If miRNA suppression is causing cancer, restore miRNA function
Define malformation and state the recurrence risk.
Malformation- structural defect of an organ resulting from the abnormal formation of tissues (flawed process of formation from the beginning), can be isolated (eg. cleft lip) or part of a syndrome (eg. cleft lip as part of Trisomy 13)
Recurrence risk: risk of inheritance of syndrome OR 3-5% if isolated
Define syndrome.
Multiple anomalies w/ a single basic cause which occur independently rather than sequentially
Define deformation and state the recurrence risk.
Structural defect resulting from tissue damage and breakdown of otherwise normal structures
Ex. premature rupture of amniotic membrane –> tendrils wrap around baby during development –> cause constriction bands around hands and feet
Recurrence risk: «1%
Define deformation.
Abnormality in form or position of a body part caused by mechanical force (constraint) or secondary effects from a functional abnormality in fetus (i.e. something gets squished)
Define sequence.
Structural defect or mechanical factor that leads to sequence of secondary effects (if –> then)
Ex. Potter sequence: renal agenesis (malformation) –> lack of amniotic fluid (baby urine) –> mechanical pressure on face, ears, hips, feet (deformation) –> lack of fluid for fetus to breathe in –> pulmonary hypoplasia (cause of death = baby can’t breathe when they’re born b/c alveoli aren’t developed)
Define uniparental disomy.
Inheritance of both homologues of a chromosome or region of a chromosome from the same parent (no copies from other parent), occurs when trisomy of fertilized ovum is rescued by loss of 3rd chromosome
