1. Special Topics in Modern Genetics: Epigenetics
Honors Genetics
Ms. Susan Chabot

2. Epigenetics Means “above” or “around” the genome.
Most recent statement; 2008 Cold Spring Harbor Epigenetics meeting:
“An epigenetic trait is a stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence.”
Alterations in the DNA sequence = mutations

3. Epigenetic Research
The number of publications in the field has increased dramatically in the last 10 years.
Genetic Engineering and Biotechnology News Feb 1, 2013 (Vol. 33, No. 3)

4. Epigenetic Effects
The role of epigenetics has been known for many years.
Lyon Hypothesis
Inactive X chromosome is heavily epigenetically modified.

5. Another Familiar Epigenetic Case
Chromosome 15 imprinting
Deletion of about 4 million base pairs.
Inheritance of chromosome 15 with deletion from mother results in Angelman Syndrome
Inheritance of chromosome 15 with deletion from father results in Prader-Willi Syndrome.
Prader-Willi Syndrome
Angelman Syndrome

6. Angelman/Prader-Willi

7. Heritable Epigenetics
Evidence suggests that environmental information could be propagated through meiosis.
Studies of Dutch famine of 1944.
Famine during last two trimesters of pregnancy:
8-9% decrease in child’s birth weight.
Offspring of these children tended to be normal size.
Famine early in pregnancy but not late:
Normal size infants were born.
Offspring of these children were low birth weight.

8. Molecular Basis Two primary mechanisms
Methylation of cytosine nucleotides in DNA
Modification to histone proteins.

9. Epigenetics and Cancer
DNA repair is a critical process to maintain genomic fidelity.
Loss of DNA repair is thought to be a major contributor to the development of cancer.
Epigenetic changes involving DNA repair genes are thought to be a major early step in cancer progression.
Turn on ONCOGENES
Turn off TUMOR SUPPRESSOR GENES
Both of the above allow cells to take on new growth properties.

10. Therapies Targeting Epigenetic
In contrast to mutations, epigenetic changes can be reversed.
There are therapies that influence epigenetic patterns and they are the focus of new chemotherapeutic agents.
Involves the reactivation of genes silenced by methylation.

11. Tumor Suppressor Genes
Turn Off
Hypermethylation
Genetic Mutations
Oncogenes
Turn On

12. DNA Microarray Typically read by a computer for the most accurate and
high-yield results.
Green dots represent genes
that are “turned off” or
under-expressed.
Red dots represent genes
that are “turned on” or over-expressed.
Yellow dots are genes that are expressed equally in both cancer tissue and healthy tissue.
Oncologists and researchers focus on the Green and Red dots for determining treatment.

13. Simulation

14. Epigenetics and Twin Studies
Comparative monozygotic (identical) twins for methylated DNA
Yellow = similar methylation pattern between twins.
Red = regions of hypomethylation in one twin compared to the other.
Green = regions of hypermethylation in one twin compared to the other.