epigenetics clyde hertzman, md human early learning partnership university of british columbia,...
TRANSCRIPT
![Page 1: Epigenetics Clyde Hertzman, MD Human Early Learning Partnership University of British Columbia, Vancouver](https://reader036.vdocuments.mx/reader036/viewer/2022070403/56649f315503460f94c4cce1/html5/thumbnails/1.jpg)
Epigenetics
Clyde Hertzman, MDHuman Early Learning Partnership
University of British Columbia, Vancouver
![Page 2: Epigenetics Clyde Hertzman, MD Human Early Learning Partnership University of British Columbia, Vancouver](https://reader036.vdocuments.mx/reader036/viewer/2022070403/56649f315503460f94c4cce1/html5/thumbnails/2.jpg)
The Challenge of the Gradient
• ubiquitous in wealthy and majority world countries by income, education, or occupation
• cuts across a wide range of disease processes
• not explained by traditional risk factors
• replicates itself on new conditions as they emerge
• occurs among males and females
• ‘flattens up’
• begins life as gradient in ‘developmental health’
![Page 3: Epigenetics Clyde Hertzman, MD Human Early Learning Partnership University of British Columbia, Vancouver](https://reader036.vdocuments.mx/reader036/viewer/2022070403/56649f315503460f94c4cce1/html5/thumbnails/3.jpg)
Sensitive Periods in Early Brain Development
Vision
0 1 2 3 7654
High
Low
Years
Habitual ways of respondingEmotional
control
Symbol
Peer social skillsNumbers
Hearing
Graph developed by Council for Early Child Development (ref: Nash, 1997; Early Years Study, 1999; Shonkoff, 2000.)
Pre-school years School years
Language
![Page 4: Epigenetics Clyde Hertzman, MD Human Early Learning Partnership University of British Columbia, Vancouver](https://reader036.vdocuments.mx/reader036/viewer/2022070403/56649f315503460f94c4cce1/html5/thumbnails/4.jpg)
Biological embedding occurs when
• experience gets under the skin and alters human biodevelopment;
• systematic differences in experience in different social environments lead to different biodevelopmental states;
• the differences are stable and long-term;they influence health, well-being, learning, and/or behaviour over the life course.
Hypothesis: Biological embedding
![Page 5: Epigenetics Clyde Hertzman, MD Human Early Learning Partnership University of British Columbia, Vancouver](https://reader036.vdocuments.mx/reader036/viewer/2022070403/56649f315503460f94c4cce1/html5/thumbnails/5.jpg)
Archeology of Biological EmbeddingArcheology of Biological EmbeddingArcheology of Biological EmbeddingArcheology of Biological Embedding
Experience/BehaviorExperience/BehaviorExperience/BehaviorExperience/Behavior
Gene ExpressionGene ExpressionGene ExpressionGene Expression
Cell/SynapseCell/SynapseCell/SynapseCell/Synapse
Neural CircuitryNeural CircuitryNeural CircuitryNeural Circuitry
![Page 6: Epigenetics Clyde Hertzman, MD Human Early Learning Partnership University of British Columbia, Vancouver](https://reader036.vdocuments.mx/reader036/viewer/2022070403/56649f315503460f94c4cce1/html5/thumbnails/6.jpg)
Shallow Archeology
Candidate Systems• HPA axis --- cortisol
• ANS system --- epinephrine/ne
• Prefrontal cortex
• Social affiliation --- amygdala/locus cereleus
• Immune function -- the ‘peripheral brain’
![Page 7: Epigenetics Clyde Hertzman, MD Human Early Learning Partnership University of British Columbia, Vancouver](https://reader036.vdocuments.mx/reader036/viewer/2022070403/56649f315503460f94c4cce1/html5/thumbnails/7.jpg)
SES Differences in Prefrontal Cortex Activity by School Age
![Page 8: Epigenetics Clyde Hertzman, MD Human Early Learning Partnership University of British Columbia, Vancouver](https://reader036.vdocuments.mx/reader036/viewer/2022070403/56649f315503460f94c4cce1/html5/thumbnails/8.jpg)
Deep Archeology
‘Social Epigenesis’ and other processes that can influence
gene expression.
![Page 9: Epigenetics Clyde Hertzman, MD Human Early Learning Partnership University of British Columbia, Vancouver](https://reader036.vdocuments.mx/reader036/viewer/2022070403/56649f315503460f94c4cce1/html5/thumbnails/9.jpg)
Epigenetics
Alterations to the DNA, other than changes to the genes themselves, that:
• are passed on with cell division
• can change normal gene expression
• can be caused by (early) experience
![Page 10: Epigenetics Clyde Hertzman, MD Human Early Learning Partnership University of British Columbia, Vancouver](https://reader036.vdocuments.mx/reader036/viewer/2022070403/56649f315503460f94c4cce1/html5/thumbnails/10.jpg)
Most well-studied epigenetic mechanism = methylation of
cytosine on the DNA
If methylation occurs in an active stretch of DNA, especially
a promoter region, gene expression will likely change
![Page 11: Epigenetics Clyde Hertzman, MD Human Early Learning Partnership University of British Columbia, Vancouver](https://reader036.vdocuments.mx/reader036/viewer/2022070403/56649f315503460f94c4cce1/html5/thumbnails/11.jpg)
The Dynamic Epigenome andThe Dynamic Epigenome andModulation of Gene ExpressionModulation of Gene ExpressionThe Dynamic Epigenome andThe Dynamic Epigenome and
Modulation of Gene ExpressionModulation of Gene Expression
![Page 12: Epigenetics Clyde Hertzman, MD Human Early Learning Partnership University of British Columbia, Vancouver](https://reader036.vdocuments.mx/reader036/viewer/2022070403/56649f315503460f94c4cce1/html5/thumbnails/12.jpg)
Maternal Diet Affects Epigenetic Gene Regulation in Isogenic Offspring (Avy /a)
Avy Expression
Avy DNA Methylation
High
HighLow
Low
Maternal Methyl
HighLow
Randy Jirtle DukeWaterland MCB 2003
Young Mice Adult Mice
Obese Lean
![Page 13: Epigenetics Clyde Hertzman, MD Human Early Learning Partnership University of British Columbia, Vancouver](https://reader036.vdocuments.mx/reader036/viewer/2022070403/56649f315503460f94c4cce1/html5/thumbnails/13.jpg)
What’s new about this?
It does not only occur during basic fetal development, when cells are specializing……it can
continue after birth and be influenced by the broader
environment!
![Page 14: Epigenetics Clyde Hertzman, MD Human Early Learning Partnership University of British Columbia, Vancouver](https://reader036.vdocuments.mx/reader036/viewer/2022070403/56649f315503460f94c4cce1/html5/thumbnails/14.jpg)
Social Environment
Gene
Health
IL6
RNA
DNA
![Page 15: Epigenetics Clyde Hertzman, MD Human Early Learning Partnership University of British Columbia, Vancouver](https://reader036.vdocuments.mx/reader036/viewer/2022070403/56649f315503460f94c4cce1/html5/thumbnails/15.jpg)
Genome
Socialprocesses
CNSfunction
Peripheralneurobiology
Cell signal transduction
Transcriptionfactors
Social signal-transduction
![Page 16: Epigenetics Clyde Hertzman, MD Human Early Learning Partnership University of British Columbia, Vancouver](https://reader036.vdocuments.mx/reader036/viewer/2022070403/56649f315503460f94c4cce1/html5/thumbnails/16.jpg)
Epigenesis at Work?
• Rats – Mothers licking pups
• Monkeys – Peer vs mother rearing
• Humans - Suicide Brains, Dunedin Cohort
![Page 17: Epigenetics Clyde Hertzman, MD Human Early Learning Partnership University of British Columbia, Vancouver](https://reader036.vdocuments.mx/reader036/viewer/2022070403/56649f315503460f94c4cce1/html5/thumbnails/17.jpg)
The ‘Meaney-Szyf Paradigm’ I
• rat pups from high and low licking/suckling mothers cross-fostered to remove genetic effect
• differential qualities of nurturance occurs during sensitive period of brain development
• differential nurturance leads to epigenetic modification of key DNA regulatory loci through methylation
![Page 18: Epigenetics Clyde Hertzman, MD Human Early Learning Partnership University of British Columbia, Vancouver](https://reader036.vdocuments.mx/reader036/viewer/2022070403/56649f315503460f94c4cce1/html5/thumbnails/18.jpg)
The ‘Meaney-Szyf Paradigm’ II
• epigenetic modification leads to lifelong change in HPA axis response to stress
• this change affects learning and behaviour across the rat life course
• inter-generational transmission (high licked female pups become high licking mothers, and vice versa)
![Page 19: Epigenetics Clyde Hertzman, MD Human Early Learning Partnership University of British Columbia, Vancouver](https://reader036.vdocuments.mx/reader036/viewer/2022070403/56649f315503460f94c4cce1/html5/thumbnails/19.jpg)
Epigenesis at Work?
• Rats – Mothers licking pups
• Monkeys – Peer vs mother rearing
• Humans – Various
![Page 20: Epigenetics Clyde Hertzman, MD Human Early Learning Partnership University of British Columbia, Vancouver](https://reader036.vdocuments.mx/reader036/viewer/2022070403/56649f315503460f94c4cce1/html5/thumbnails/20.jpg)
1958 cohort, WBC’s, age 45
• 1252 loci differentially methylated according to childhood SES (smaller signatures for adult SES and social mobility)
• 794 loci differentially methylated by maternal smoking
• >1000 loci differentially methylated by retrospective reports of abuse in childhood
![Page 21: Epigenetics Clyde Hertzman, MD Human Early Learning Partnership University of British Columbia, Vancouver](https://reader036.vdocuments.mx/reader036/viewer/2022070403/56649f315503460f94c4cce1/html5/thumbnails/21.jpg)
Different populations?
The Wisconsin Study of Families and Work
• methylation differences according to mother stress in first 18 months, not father’s stress…… but in pre-school age, father’s stress, not mother’s, influences DNA methylation
The BC GECKO Study: ‘On and Off-diagonal children’ in ‘On and Off-diagonal neighbourhoods’
![Page 22: Epigenetics Clyde Hertzman, MD Human Early Learning Partnership University of British Columbia, Vancouver](https://reader036.vdocuments.mx/reader036/viewer/2022070403/56649f315503460f94c4cce1/html5/thumbnails/22.jpg)
Common FocusCommon Focus
Developmental neurogenomics: how developmental environments and epigenetic variation work together to produce social disparities in child health and development
Developmental neurogenomics: how developmental environments and epigenetic variation work together to produce social disparities in child health and development
![Page 23: Epigenetics Clyde Hertzman, MD Human Early Learning Partnership University of British Columbia, Vancouver](https://reader036.vdocuments.mx/reader036/viewer/2022070403/56649f315503460f94c4cce1/html5/thumbnails/23.jpg)
BC capacity
• Kobor lab -- social epigenetics facility; multiple funding sources
• 450,000 CpG island capacity; covering all genes
• emerging as reference facility for Canada, US, and global studies
![Page 24: Epigenetics Clyde Hertzman, MD Human Early Learning Partnership University of British Columbia, Vancouver](https://reader036.vdocuments.mx/reader036/viewer/2022070403/56649f315503460f94c4cce1/html5/thumbnails/24.jpg)
www.earlylearning.ubc.cwww.earlylearning.ubc.caa
Thank YouThank You
Our Funders:Our Funders: