Special Topics in Modern Genetics:Epigenetics

Honors Genetics 2013-2014Ms. Susan Chabot

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

Epigenetic ResearchThe 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)

Epigenetic Effects• The role of

epigenetics has been known for many years.

• Lyon Hypothesis - 1961.• Inactive X

chromosome is heavily epigenetically modified.

Another Familiar Epigenetic Case

Prader-Willi SyndromeAngelman Syndrome

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.

Angelman/Prader-Willi

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.

Molecular Basis

• Two primary mechanisms• Methylation of cytosine

nucleotides in DNA• Modification to histone

proteins.

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.

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.

Tumor Suppressor Genes

Genetic MutationsHypermethylation

Oncogenes

Turn Off

Turn On

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.

Simulation

http://learn.genetics.utah.edu/content/labs/microarray/

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.