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Flashcards in Genetics Deck (33):

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?



What happens if epigenetic regulations aren't working properly?



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?

-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

-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


What happens in an embryo if uniparental disomy involves a segment of a chromosome? An entire chromosome? The entire genome?

Segment of a chromosome: 2 chromosomes are present, but there are regions of homozygosity and regions of heterozygosity-- can result in Prader Willi syndrome (maternal UPD) or Angelman syndrome (paternal UPD)

Entire chromosome: 2 copies of the exact same chromosome

Entire genome: ovarian teratoma (all maternal contribution) or hydatidiform mole of placenta (all paternal contribution)


What role does epigenetics play in cellular differentiation?

Oocyte and sperm have CpG methylation --> after fertilization, sperm immediately demethylates, but oocyte is slower

Before nuclei fuse, one round of DNA replication occurs --> remethylation begins to appear (opportunity to "reset" methylation)


What role does imprinting play in cloning of organisms and stem cells?

A lot of bad things happen when cloning organisms and stem cells, and imprinting would just make it worse


Define morphigenesis.

Shape of embryo is produced through axis development (craniocaudal, anteroposterior) and asymmetry development (determined by families of transcription factors)


What are HOX genes?

Family of developmental transcription factors (helix-turn-helix family) that binds right into DNA groove to influence transcription

Form in 4 clusters on 4 chromosomes

Form a temporospatial arrangement- they are on the same chromosome and are closely related, but act at different times to cause development of different organs/parts of the body


Define morphogens and describe their mode of action.

Morphogens- small molecules that diffuse and create concentration gradient --> gradient has different effects on cell fates

Mode of action: bind to receptors of intracellular inducible transcription factors


Provide examples of small molecules that are morphogens.

Retinoic acid (binds near HOX genes), steroid hormones, thyroxine

NOTE: Isotretinoin (13-cis-retinoic acid) has a low affinity for retinoic acid receptors but may be converted intracellularly to metabolites that are agonists --> contraindicated in pregnancy b/c of teratogenicity (causes birth defects in children like hydrocephaly, microcephaly, intellectual disabilities, ear and eye abnormalities, cleft palate and other facial deformities, heart defects)


Define induction.

Process by which 1 part of an embryo causes adjacent tissues to change through diffusion of substances


Define sequential induction.

Morphogens released in a series of signals provided by different agents cause induction