Epigenetics 101 Why Grandmothers are Important

Transcription

1 Epigenetics 101 Why Grandmothers are Important Dian Baker PhD, APRN, PNP Photo from: welcomebooks.com

2 Learning Objectives Describe the basic concepts behind epigenetics Discuss why the epigenome is sensitive to maternal (and maybe paternal), nutrition stress, and environmental exposures Explain why epigenetics may provide a mechanism for prevention of behavioral disorders

3 To meet our objectives: 1. Review basics of DNA, genes, genomes 2. Overview of epigenetics 3. How might epigenetics impact behavior and development? 4. What does the future hold? Contact information: Dian Baker

4 What is everyone talking about?

5 I am the beneficiary of a lucky break in the genetic sweepstake Isaac B. Singer Epigenetics OR NOT? Photo from:

6 Overview of the Basics What s a gene? What is DNA? 3 billion chemical based pairs What s a genome? 25, 000 to 30,000 indentified genes Except for Red Blood Cells all human cells have a complete genome 99% of all nucleotide bases are the same in all humans What s epigenetic? in addition to the genome

7 Double Helix Overview of the Basics

8 DNA and GENES Instructions to grow and live reside in the nucleus of every cell These instruction are in a molecule DNA your human blueprint Twisted ladder double helix 4 letter alphabet A always pairs with T, and C always pair with G G Guanine A adenine T thymine C cytosine

9 DNA We have about 3 meters of DNA in each cell, how does it fit? It turns and twist in a ladder DNA information is packed into chromosomes Chromosomes are tightly packed DNA with a protein wrapper (histone) Humans have 46 chromosomes, one set of 23 each from mom and dad

10 Instruction manual made up of DNA molecules Provide directions for building all the proteins in our bodies What is a gene? About 30,000 genes each with special sets of instructions not all are used, all the time in fact, most are not!

11 Genes special set of instructions Each cell makes use of its genetic materials in a different way that is why the heart is the heart, and the ear is the ear Functional genes turn on and turn off certain parts of the DNA materials Housekeeping genes keep things in order

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13 Telomeres and Aging Ends of chromosomes telomeres Telomeres protect our genetic data Like the plastic tip of a shoelace, protect the gene from fraying and sticking together Each time the cell divides the telomeres get shorter and less protective this process is assoc with certain cancers and aging

14 What does it look like really?

15 What about Epigenetics? Epigenetic changes influence the phenotype without altering the genotype. - Benjamin Lewin Photo from: stochasticsscientist.blogspot.com/2010/05/grandmotherfavorite

16 Epigenetics Waddington 1942 Intersection of ecology, development, evolution and genetics Can change the phenotype without alteration of the genome but changes can persist across generations Environment can drive alteration in the epigenome 3 mechanism DNA methylation Histone modification Non-coding, duplication RNA Photo from:christs.cam.uk/cms/misc/images Ho & Burggren J of Exp Biology. 2010, 21, 3-16

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18 Turn on and off the tape players Epigenetics Currently know of 3 knobs on the controls RNA Nucleosome DNA methylation

19 DNA + histones make Chromatin

20 Imagine from: publications.nigms.nih.gov/.../repairingdna.htm Repair of DNA

21 Red Dots Epigenetic Methylation sites in the genome Photo from: Nova Ghost in your Genes

22 The Epigenome at a Glance2 netics/intro/

23 An example epigenetics at work The Agouti Sisters Twin Mice Next set of Agouti Sister slides and photos from Jirtle & Waterland Duke University

24 Agouti Gene

25 What happens in stressful situations? Stress and Epigenetics Stress Circuit HPA Axis (hypothalamus-pituitary-adrenal)

26 Nurturing Mothers When mothers lick their pups and nurture them, epigenetics come into to play More receptor sites to stabilize stress hormones are established in the licked rats The increase in receptor sites passes to the next generations

27 Is it inherited? Just as the genome is passed along from parents to their offspring, the epigenome can also be inherited. The chemical tags found on the DNA and histones of eggs and sperm can be conveyed to the next generation.

28 Imitating Nature with Science

29 Epigenetics at work Important environmental flexibility Reaction to stress can be a good thing, it depends on the environment Stressful environments make stressed, less nurturing moms but the offspring may need to have excellent stress reaction be alert and anxious Jirtle & Waterland

30 Epigenetics are intergenerational Its your grandmother! Part of the genome get turned on and off for the eggs developing inside the young female Environment, hereditary, stress, nutrition, etc. during your grandmother s pregnancy with your mom affect you!

31 Grandpa & Dad s role in epigenetics Still not clearly understood Environment does matter Boys ages 9-12 have a slow growth period and ready for spermatogenesis Nutrition ( and possibly stress) during this time correlation to grandchildren s life span diabetes and heart disease

32 Photo from: Learn.genetics.utah.edu/ epigenetics/twins

33 Epigenetics and Disease MOST epigenetic changes are harmless However current research projects are examining epigenetics and genomic links for hundreds of diseases (PudMed - 37,194 hits) Cancer Leukemia has active trials ongoing Obesity Irritable Bowel Syndrome Personality Disorders (Maladaptive Disorders) Schizophrenia multiply studies Autism Muscle Disorders Mitochondrial Disorders Dental Disease Addiction

34 Just some epigenetics disease From: nature.com/nated

35 Epigenetics and Behavior Mental health semaphorins and the frontal cortex Advancing paternal and maternal age & cognitive function Reichenberg (2010) Cog Neuropsy, 14(4), 337 Suicide and child abuse McGowan et al. (2009) compared brains of suicide victims with those that died in car accident found significant differences in methylation glucocorticoid (stress) receptors Disruptive behaviors Tremblay (2010) J Child Psy and Psych 51(4), 341

36 Epigenetics and Autism Multiple links to epigenetics and a role in autism Fragile X, Rett Syndrome Maternally deprived duplications imprinted on chromosomes 15q11-13 and 7q Mitochondrial disorders Epigenetics from imprinting do not show on genomic sequencing Shanen, C. (2006). Human Molecular Genetics, 15(2), R138.

37 Autism & Epigenetic con t Monozygotic twins discordant for Dx of autism Microarray analysis lymphoblastoid cell lines Methylations profiling differences between the discordant twins, and between siblings Methlation status difference in gene transcription, nervous system development, cell death/ survival all implicated in autism Nguyen AT, Rauch TA, Pfeifer GP, Hu VW. The FASEB Journal, April 2010

38 Epigenetic Autism and ADHD A few examples Impaired methylation and mutations of mecp2- autism (RETT & Angelman Syndrome) Currenti (2010). Cell Mol Neurobiolo,30,161. DNA hypomethylation of folate maternal carrier gene James et al. (2010). Am J Med Gen B Neuropsy Genet, May Epigenetic and Cognition Miller (2010). Science, July, 329,27. Abstract thinking Horner (2009). J Am Acad Child Adol Psy,48,1047.

39 Epigenetics, Nutrigenomics and Environment From:HealthMatterstoMe.com

40 Epigenetics, Nutrigenomics and BPA and the The Twins Environment Good news Maternal Diet and the The Agouti Twins Maternal nutrition matters BUT don t count Dad out

41 Pharmcogenomics Food Drug Administration (FDA) consider clinical implications of genomics Racial and ethic differences About 10% drug labels now consider genes Warfarin Atomoxetine (ADHD medication simulate) Variability in metabolism to CYP2D6 Variant alleles effect metabolism over or under metabolize (Michelson et al. 2007) FDA (2007)Table of valid biomarkers/genomics/

42 Epigenetics, You and Your Family

43 Surgeon General Family Health

44 What about you?

45 What about popular myths? Genes inherited from parents do not set your life course in stone Adverse fetal and childhood experiences can lead to chemical changes and epigenetic changes Despite some marketing there is no evidence that enrichment programs can change the epigenome or enhance brain function From: Nat Scientific Council of Developing Child Harvard University Early Experiences can alter gene expression and affect long-term development working paper #10

46 What might be recommended? High quality health services and nutritional support for families Avoiding exposure to known environmental toxins and toxic substances Epigenetic changes happen across generations reduce stress, economic insecurity Education for teachers, healthcare providers, caregivers, families, and the general public about epigenetics From: Nat Scientific Council of Developing Child Harvard University Early Experiences can alter gene expression and affect long-term development working paper #10

47 Researchers at UCD, Jorge Dubcovsky and colleagues, improving wheat through epigenetics Avoiding the controversy regarding genetic engineering IN the future

48 Important Ethical Questions for our Future

49 The Ghost in Your Genes /wgbh/nova/genes/ mice.html

50 QUESTIONS Photo from wordpress.com