Updated: 4/2/2020

Epigenetics

0%
Topic
Review Topic
0
0
N/A
N/A
Questions
4
0
0
100%
0%
Evidence
2
0
0
Topic
Overview
  • Changes in gene expression caused by mechanisms other than changes in actual DNA sequence
  • Examples
    • X-inactivation
    • imprinting
    • histone modification
      • see Chromatin structure topic
X-inactivation 
  • Overview
    • normalizes the genetic amount of males and females (lyonization)
    • inactivates # of X chromosomes - 1 in a Barr body
      • triploid X will have 2 Barr bodies
  • Mechanism
    • mediated by XIST gene
    • inactivation through methylation
    • occurs at blastocyst stage in female embryos
    • X copy chosen for inactivation is random
      • after choosing every subsequent cell will have the same X copy inactivated
  • Clinical relevance
    • mosaicism
      • non-homogenous X inactivation
      • some cells express paternal X and some cells express maternal X
Imprinting
  • Overview
    • describes differences in transcriptional activity based on whether the chromosome is of maternal or paternal origin
    • at a single locus
      • 1 allele is active
      • 1 allele is inactive
    • creates a hemizygous state
  • Mechanism
    • inactive ("imprinted") allele is methylated during gametogenesis
      • creates transcriptional inactivity
    • is maternal/paternal specific
      • gene at one locus always methylated on a specific copy
    • all cells of an individual have same imprinting level
    • during gametogenesis of the individual the methylation state is erased
      • reset to be either maternal or paternal depending on the sex
  • Clinical importance
    • Prader-Willi syndrome  
      • cause
        • deletion or mutation of normally active paternal allele on 15q
        • remember: Prader = paternal deletion
      • presentation
        • mental retardation
        • hyperphagia → obesity
        • hypogonadism
        • neonatal hypotonia
        • behavior problems
      • affects both male and females
    • Angelman's syndrome 
      • cause
        • disruption of the maternally expressed and paternally imprinted gene UBE3A, which encodes an E3 ubiquitin ligase 
        • typically results from deletion of the normally active maternal allele on chromosome 15q
          • same region of the genome as Prader-Willi syndrome deletion but opposite chromosome (not the same gene)
      • presentation
        • severe cognitive disability
        • frequent seizures
        • ataxia
        • speech impairment
        • hyperactivity
        • inappropriate laughter
          • "happy puppet"
      • affects both male and females

Please rate topic.

Average 4.6 of 5 Ratings

Questions (4)
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK
Evidence (2)
EXPERT COMMENTS (19)
Private Note