Transcription
Randy L. Jirtle, Ph.D.!Department of Radiation Oncology!Duke University Medical Center!Durham, NC 27710Origins!Artist: !Collin Murphy!
“Epigenetics is now the hottestthing in bioscience!” Randy Jirtle!Nevertheless, a number ofadministrators and scientists!Fetal Origins!Studies!Imprinting Evolution !Studies!*!Still!Just!Donʼt!Get! It!!Scientific Community: Doubling ofepigenetic papers every two years !http://www.geneimprint.com!
DUTCH FAMINE (1944-1945)! 16,000 people died !CHINESE FAMINE (1959-1961)! 20 to 40 million people died!Miracle Occurs!Artist: Sidney Harris!Miracle: Epigenetic Modifications!Waterland et al. Mol. Cell Biol. 23: 5293-5300, 2003!http://www.geneimprint.com!
The Agouti Sisters!
seudo-!agouti!3ʼ!!AvyIAP!5ʼ!A, a5ʻ!!1A!!3ʻ! 15 KbPS1A!4.1 Kb!!!!!!!!!!!!!! !!!! ! 100 KbControl Diet!100Supplemented Diet!40!(Folic acid, Vitamin B12, !Choline chloride and !Betaine) p 0.008!30!20!10!0!!Control Diet!Cells Methylated (%)Avy Offspring (% of Total)!50!Yellow!Slightly! Mottled! Heavily! Pseudo-!Mottled!Mottled! agouti!Waterland et al. Mol. Cell Biol. 23: 5293-5300, 2003!!!!!!!!!!!!! !!!! !!!Supplemented Diet!10090908080707060605050404030302020101000 1 2 3 4 5 6 7CpG Site in Avy PSIA!2!!00 1 2 3 4 5 6 7CpG Site in Avy PSIAPseudo-agouti!80%!Heavily Mottled!50%!Mottled!26%!Slightly Mottled!13%!Yellow!7%!!http://www.geneimprint.com!
Agouti Coat Color!Distribution!Control Diet!Dietary Supplementation!Methyl Donors or Genistein!Counteracting Forces !Artist: Collin Murphy!“Let food be thy medicine, and !medicine be thy food.” Hippocrates!Dolinoy et al., PNAS 104: 13056-13061, 2007!Endocrine Disruptor Exposure !Bisphenol A (BPA)!BPA Exposure plus!Methyl Donor or om!
http://www.geneimprint.com!
Artist: Pat Sherwood
“All animals are equal, but some animals !are more equal than others.” George Orwell!http://www.geneimprint.com
McGrath and Solter Cell 37: 179-183 1984 !Surani et al. Nature 308; 548-550, 1984http://www.geneimprint.com!
Imprinting results in parent-of-origin dependentmonoallelic expression. !CTCF!Mat!Human 11p15.5!Pat!ICR!http://www.geneimprint.com
“Nothing in biology makes sense exceptin the light of evolution.” Theodosius Dobzhansky!Theodosius Dobzhansky!(1900 -1975)!http://www.geneimprint.com
Primates!Scandentia!IGF2R !Imprinting Lost !(75 M Years Ago)!Artist: James Jirtle!IGF2R & IGF2 !Imprinting Evolved !(150 M Years Ago)!Dermoptera! !Birds!Killian et al. Mol. Cell 5: 707-716, 2000!Killian et al. Hum. Mol. Genet. 10: 1721-1728, 2001!Evans et al. Mol. Biol. Evol. 22: 1740-1748, 2005!http://www.geneimprint.com!
Biological responses due to imprintingdysregulation will be difficult to extrapolatebetween species, making it ʻchallengingʼto generate relevant animal models. ! Mice are not humans!!http://www.geneimprint.com!
SchizophreniaAutism!The Imprinted Brain!Artist: !Collin Murphy!Keverne et al., Brain Res. Dev. Brain Res. 92: 91-100, 1996 !Badcock and Crespi, Nature 454: 1054-1055, 2008!Badcock, The Imprinted Brain, 2009!http://www.geneimprint.com
Autism is the antithesis of schizophrenia.!Nutrition excess may increase thesusceptibility to autism with a concomitantdecrease in psychosis formation. !Without knowing the repertoire of humanimprinted genes and their regulatoryelements, The Imprintome, the ability todiagnosis, treat, and prevent neurologicaldisorders like autism and schizophrenia willremain compromised. !http://www.geneimprint.com!
Identify human imprinted genes and theirepigenetically-controlled regulatoryelements - The Imprintome.!Determine the role of imprinting in humandiseases and neurological disorders.!Artist: James Jirtle!Luedi et al . Genome Res. 17: 1723–1730, 2007!http://www.geneimprint.com!
Artist: Pat Sherwood!
Origins! Artist: !Collin Murphy! Randy L. Jirtle, Ph.D.! Department of Radiation On
