Epigenetics and Abnormal Gene Expression Flashcards
What is epigenetics?
Heritable modifications of DNA that do not alter the primary sequence resulting in altered gene expression
What is DNA methylation?
Addition of methyl group onto C5 of a cytosine group.
How can DNA methylation lead to gene silencing
Most genes have GC base rich areas in DNA promoter region called CpG island. Methylation of C residues in these CpG islands leads to gene silencing.
How can DNA methylation inhibit gene transcription
It prevents the binding of transcription factors to the promoter and converts chromatin to a closed conformation.
How else can DNA methylation favour compact chromatin?
It recruits proteins such as histone deacetylases which removes acetyl groups.
Describe clinical features of Prader-Willi syndrome
Paternal gene deficiency leading too Mental retardation and obesity.
Describe clinical features on Angelman syndrome
It is a maternal gene deficiency leading too Mental retardation, “happy puppet syndrome”, jerky movements and inappropriate laughter.
Describe features of heterochromatin
It is highly condensed (in interphade), it only contains a few genes so is transcriptionally inactive and replicates late in S phase
Describe features of Euchromatin
Organised in 30nm fibres (in interphase), transcriptionally active and replicates early in S phase
What is the position effect?
The spreading of heterochromatin into euchromatin regions causing cell to cell variability in gene expression. It can also inhibitory
Why must females silence one X chromosome
Because males have 1 X- chromosomes but females have two
How are X chromosomes so;enced?
Initiated by Xist which marks the inactive chromasome and is only expressed on that chromosome, codes for RNA.
Followed by DNA methylation
What is Klinefelter’s Syndrome?
When males have an extra X chromsome so are XXY. One X must undergo inactivation
What is Rett Syndrome?
X-linked neurodegenerative disorder caused by mutation in the gene encoding the Methyl-CpG binding protein 2, leading to the loss of gene silencing.
What are imprinted genes?
Genes that are only expressed from one allele which is dependant on parental origin
