Special Topics in Modern Genetics: Epigenetics Honors Genetics Ms. 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 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)

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

Another Familiar Epigenetic Case Prader-Willi Syndrome Angelman 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 – 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

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.