Epigenetics: Lect 14

Question 1

Epigenetics

Answer 1

• a change in the expression of a gene; changes the phenotype w/o permanently changing the gene.
• changes in chromatin structure
• heritable

Question 2

Euchromatin

Answer 2

decondensed and transcriptionally active

Question 3

Heterochromatin

Answer 3

condensed and transcriptionally inactive.

Question 4

Methylation process

Answer 4

1. Dnmt3 methylates unmethylated DNA.
2. MeCP2 recruites either HDAC1 or Dnmt1.
3. HDAC1 deactylates histones.
4. Dnmt1 methylates hemimethylated DNA (maintains methylation pattern that Dnmt3 did)

Question 5

HATs

HDACs

Answer 5

• acetylates histones.

- deacetylates histones

Question 6

Methylation of globin genes during fetal development:

• Epsilon gene:
• Gamma gene:

Answer 6

6wks: Epsilon is active/unmethylated
12wks: Gamma is active/unmethylated

Question 7

ICF

Answer 7

• Immunodeficiency-centromeric instability-facial anomalies syndrome.
• rare AR disease
• mutation in Dnmt3b gene
• facial dysmorphism, mental retardation, recurrent infections and immune deficiency w/ constant decrease of IgA.
• centromere instability of chrom 1, 9, 16.

Question 8

Rett Syndrome

Answer 8

• females more affected
• nl males die in utero but seen in Klinefelter male.
• nl development until 6-18 months
• loss of speech/acquired hand skills. Seizures, repetitive hand movements, irreg breathing and motor control problems.
• mutation in X-linked MeCP2 gene.

Question 9

Biallelic expression

Answer 9

• both alleles of a gene “maternal and paternal” are expressed.
• Genomic imprinting/”Gamete of origin dependent modification of phenotype” is characterized by mono-allelic expression.

Question 10

Prader-Willi syndrome

Answer 10

• missing SNRPN gene product
• hypotonia, failure to thrive in infancy, wt gain, round face, almond shaped eyes, hypogonadism, voracious appetite, short stature, hypopigmentation, hypothalamus hypofunctions.

Question 11

Angelman syndrome

Answer 11

• missing UBE3A gene product
• happy puppet, always smiling/happy. Severe developmental delay, little or no speech, movement or balance disorder, hyperactive.

Question 12

Beckwith-Wiedemann Syndrome

Answer 12

• maternal chrom rearrangements of 11p15 (imprinted region)
• paternal uniparental disomy
• abnl methylation at 11p15
• macroglossia, high birth wt/length, umbillical hernia, increased risk of cancer, neonatal hypoglycemia.
• IVF increases risk (causes abnl methylation at 11p15)

Question 13

Environmental factors that influence/disrupt epigenetic gene silencing.

Answer 13

Temperature, toxins, maternal care, diet, hypoxia.

Question 14

Environmental exposures influence?

Answer 14

-mothers (1st gen), fetus (2nd gen) and offspring of fetus (3rd gen)

Question 15

Orexin:

Answer 15

involved in regulating feeding behavior and sleep/wake and lipid metabolism.
-expressed when epigenetic glucose sensing switch causes DNA hypomethylation and histone acetylation.

Question 16

Calico Cat

Answer 16

process of X-inactivation; all females are mosiac

Question 17

Incontinentia pigmenti

Answer 17

• mutation of the X-linked IKBKG gene.

- lethal in males, survived in females w/ skewed X-inactivation.

Question 18

Gene subject to genomic imprinting show what pattern of inheritance?

Answer 18

-none, it depends on the sex of the parent contributing to the mutant gene.