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1. Messinger Genetics and Prenatal Development
D. Messinger, Ph.D.
2. Rutter, M. (2002). Nature, nurture, and development: From evangelism through science towards policy and practice. Child Development, 73, 1-21. dg Messinger
3. Nature: Genetic Risk and Protective Factors Quantitative genetics:
Quantifies the strength of genetic and non-genetic factors
Have increasingly been finding interplay between genetic and non-genetic factors
Genetics believed to play role in all traits, with non-genetic influences also important in gene-environment interactions, environment may have more/less impact on those who are/are not genetically susceptible
Problem of misleading claims (e.g. only mentioning nonshared effects, inferences made from overstated claims)
Identification of specific genes involved in susceptibility
Some individual genes have been identified in liability to mental disorders; some also associated with variations in response to environmental hazards or medication
Future advances should try to understand causal processes involved in disorders and facilitate studying environmental risks Gangi
4. Nurture: Environmental Risk and Protective Factors Risk/protective factors involve immediate family, peer group, school, and broader community
Research has consistently shown the psychopathological risks associated with some environmental factors (e.g. discord and conflict, lack of personal caregiving, etc.)
Distinction between proximal (direct) and distal risk processes
Now some evidence supports specificity of effects; many adverse experiences may also involve a range of elements each carrying specific risks
Future research growth will be gene-environment interplay genetic vulnerabilities may operate by increasing susceptibility to environmental hazards Gangi
5. Developmental Processes Awareness of importance of epigenetic and chance effects
Some variations will show a pattern at a group level, but be unpredictable at the individual level
For developmental programming: dependent on having experiences within a broad range (experience expectant), also provides adaptation to environments experienced (experience-adaptive)
Research should consider diversity of causal processes, including genetic, environmental, and developmental processes Gangi
6. Messinger Class What are the advantages (name some forms of genetic transmission) and disadvantages of thinking of genes as blueprints?
How do environmental and genetic influences interact during prenatal development (provide examples)?
What is the difference between transactional and a behavioral genetics approach to gene * environment interactions?
7. Messinger Nature genetics
Genes as blueprint
Genes, environment, and their interaction accounting for outcome?
8. Messinger Some basics Genes
Bits of DNA, protein, in each cell
contain information on cell functioning, production, and reproduction
Larger groupings of DNA
All non-gamete cells in the body have 23 pairs of chromosomes
Half of each pair came from each parent
9. Messinger Chromosomes
10. Messinger Human genome project identify all the approximately 30,000 genes in human DNA,
determine the sequences of the 3 billion chemical base pairs that make up human DNA,
99% (of nucleotide bases) are the same in all people
11. Messinger Detailed description
12. Messinger UM Genetic Researchers Publish New Autism Findings Geneticists at the University of Miami Leonard M. Miller School of Medicine, havelocated a region of chromosome 12 that they believe harbors a new gene related to autism. Molecular Psychiatry.
Defects in many as 20 different genes may cause autism in a single individual, and these genes are not necessarily the same ones that cause the disease in another autism patient, she said.
The researchers screened the entire genome -- the body's genetic blueprint -- of 26 extended families with at least two members with autism, looking for regions of "linkage" where DNA variations appeared to be inherited along with the disease.
184 people, 65 of whom were affected with autism. They found a novel region -- a small section of the long arm of chromosome 12 -- that appeared to contain a gene that causes autism.
We have identified the smallest candidate region for a new autism gene, and with the highest statistical confidence, of any other study to date, Haines said.
When the Duke study focused on families in which only males were affected, the evidence for linkage to this same region was enhanced significantly. The finding adds to the growing evidence that the causes of autism may be different between males and females, and suggests that this difference could stem from a gene that lies within this region of chromosome 12, Haines said.
According to the researchers, 19 genes are located within this candidate region. They are currently sequencing these candidate genes for genetic variations present in those individuals affected with the disease but not in their healthy relatives.
13. Messinger Disadvantages of the genes-as-blueprint metaphor Genes are bits of protein in a primarily liquid nucleus in a primarily liquid cell surrounded by other cells in a primarily liquid uterine environment
Without an environment, genes are bits of protein
From a lump of jelly to an organism
How do genes actually work?
14. Messinger Genomes to Life Project - Proteomics Identify the protein machines that carry out critical life functions and the gene regulatory networks that control these machines
15. Messinger Terms Phenotype
The broader phenotype (autism)
Genetic pattern associated with the phenotype
16. Messinger Polygenic inheritance not blue-print inheritance - is the rule Multiple genes influence most traits
Sign of polygenic inheritance is range in phenotype rather than either or
skin/eye/hair color, height, baldness, personality
Potential variability in expression of a trait
Such traits may also be susceptible to environmental influence
17. Messinger How are genes a blueprint? The DNA sequence (e.g., ATTCCGGA) . . . spells out the exact instructions required to create a particular organism with its own unique traits.
A metaphor which describes cases in which there is a specific correspondence between genotype and phenotype
18. Messinger Blueprint-likemodes of genetic transmission Dominant-recessive
Single gene or Mendellian
Specific genetic defects can be deadly or disabling
sickle cell, phenylkitenuria (but see Knox & Messinger, 1958), etc.
Sex-linked (23rd chromosome)
19. Messinger Dominant-Recessive Inheritance Traits are transmitted as separate units
Autosomes - 22 pairs
One pair from each parent
When 2 competing traits are inherited
Only 1 trait is expressed
20. Messinger Dominant-Recessive Inheritance
21. Messinger Sex-linked inheritance 23rd chromosomal pair
Male = XY (Missing an arm)
one Y branch not matched
so allele on corresponding X branch is expressed
Female = XX
each branch is matched
22. Messinger Sex-linked inheritance Males x inherited from mother
Women are carriers
Males represented disproportionately in sex linked disorders
23. Messinger Quantitative perspectives on gene*environment interface The influence of genetic and environmental factors be distinguished and the influence of each can be quanitified using behavioral genetic methods (Plomin)
24. Messinger Behavioral genetics Measuring genetic and environmental influences on behavior
Finding genes for behaviors?
25. Messinger Twin Studies
26. Messinger Twin studies Identical (MZ) twins share 100% of their genes
Fraternal (DZ) twins share 50% of their genes
Both types of twins have similar environments . . .
Greater behavioral similarity of identical twins indexes greater genetic influence
27. Modeling differences between correlations Messinger
28. Messinger No genetic influence
29. Messinger Genetic influence
30. Messinger Genetic Influence on Human Psychological Traits: A Survey There is now a large body of evidence that supports the conclusion that individual differences in most, if not all, reliably measured psychological traits, normal and abnormal, are substantively influenced by genetic factors. (Bouchard, 2004)
Bouchard, T. J. (2004). "Genetic Influence on Human Psychological Traits: A Survey." Current Directions in Psychological Science 13(4): 148-151.
32. Messinger Sources of Variance in Behavior Genetic (heritability)
Gene x environment interaction
33. Messinger Estimates of genetic and environmental influence Proportional in samples
Greater environmental variation
Will minimize genetic variation
Greater genetic variation
Will minimize environmental variation
E.g. Downs Syndrome
34. Messinger Environmental effects Previously modeled but not measured
Now parental monitoring, neighborhood deprivation account for small (2-5%) of environmental variation
What else should we be measuring?
35. Messinger Gene * Environment interactions Development always involves this interaction
Specific statistical effects
Genetic effects on alcohol use are great in non-religious than religious households
Genetic effects on seeking specific environments
Identical twins find similar friends
Identical twins treated more similarly (or differently) than fraternal twins?
36. Messinger Questions Why might adoption studies maximize estimates of genetic influence?
Can genetic effects increase with time?
37. Messinger Transactional perspective on gene*environment interface It is not nature vs. nurture, but the interaction of nature and nurture that drives development. Urie Bronfrenbrenner
38. Messinger Gene*Environment Interaction
39. Messinger Gene * environment interactions
40. Messinger Reaction range: Genetic constraints on environmental variability
41. Messinger Demonstrates importance ofG*E
42. Messinger What will it take to make behavioral genetics truly developmental? In my opinion, the purely statistical population view will have to be abandoned in favor of the study of individuals:
An analysis of the bi-directional relations from gene action to the external environment over the life course, including the prenatal period.
Gottlieb, G. (2003). "." Human Development 46(6): 337-355.
43. Messinger Transactional model
44. Measured Gene-Environment Interactions and Mechanisms Promoting Resilient Development.(Julia Kim-Cohen & Andrea L. Gold, 2009) Veronica Fernandez Fernandez
Gene-environment interactions (G x E)
Environmental risks that interact with genes to predict vulnerability and resilience
46. Individuals carrying protective allele have significantly reduced levels of psychopathology than those that posses the vulnerable allele
In maltreated children:
low vs. high levels of monoamine oxidase (MAOA) enzyme expression
short vs long serotonin transporter (5-HTT) gene
No effect on individuals that had not been exposed to risk
(Caspi & Moffitt, 2006)
48. Methylation can mask the transcription of certain genes Messinger
49. Messinger Epigenetic breakdown. Several epigenetic mechanisms alter gene activity in neurons, with potentially important effects on brain function and behavior.
Histone acetylation tends to promote gene activity,
whereas histone methylation and DNA methylation tend to inhibit it.
50. Interactions between genetics and environment should be examined as we move past nature and nurture.
Support for Gene by Environment Interactions
Cooper and Zubek (1958) Maze studies on rats - despite genetic predisposition environment plays a role.
Dunedin Longitudinal Study (Caspi et al., 2003)- Low serotonin transporters only see greater risk for depression in high-stress conditions.
sites based on cell conditions.
Could lead to a particular gene not being expressed. Matson
51. The Seductive Allure of Behavioral Epigenetics. Miller (2010) Molecular mechanisms that alter gene activity
Do not change the DNA sequence
Early life experience leads generational effects
Could be at the heart of many problems
SES, drug addiction, abuse?
Szyf & Meany (2004) rat research begins inquiry
Less nurturing mothering leads to poorer stress response
Poorer stress response, fewer Corticosterone receptors
Linked to DNA methylation
Enzymes reverse methylation, improve receptor numbers
52. Epigenetics in Rodents Champagnes extension to later mothering
Less mothering attention -> Greater methylation
Less mothering attention in the next generation
Starting to look at communal mothering effects
Roth and Sweatt (2009)
Stressed mothers spend less time nurturing
Lower BDNF hormone -> Greater methylation - > Lower neural growth
Linked to anxiety in mice, responds to antidepressants
Miller and Sweatt (2007)- Inhibition of methylation ?detrimental to memory
Nestler et al. (2010) Cocaine exposure
Higher acetylation and methylation of histones
Stimulates reward circuitry
When manipulated increases response Mattson
53. Which is better? Messinger
54. What Can Methylation Mean for Rats? Weaver (2004) - GR Gene in Rodents - Drugs introduced in adult rats targeting this gene can affect stress response, reducing response to the level of rats who received low maternal care. Matson
55. Epigenetics in Humans Hard to get brain tissue, Indirect sampling
Szyf & McGowan (2009)
Post-mortem examinations of 24 suicides
More methyl groups in glucocorticoid receptor genes of abused
Oberlander et al. (2008)
Umbilical cord blood, higher methylation and higher later cortisol, increased suceptability to stress
Miller et al. (2009)
Greatly impaired immune function in lower SES
No epigenetic effects in white blood cells
Social interactions regulate gene expression
Different tissues, different ways
Need a directed search rather than just epigenetic flags
Twin studies, particularly Fraga's (2005), indicate genetic variation between young and old monozygotic twins Mattson
56. True or false? Inherited DNA determines gene expression through the lifespan
Environmental factors for generation 1 can influence gene expression in generation 2 Messinger
57. Environmental Pathogen High depressive symptoms with carriers of low-activity MAOA allele
Effects of multiple types of maltreatment
Resilience can be due to variability in exposure to environmental risk factors
Accuracy of risk exposure
(Cicchetti, Rogosch & Sturge-Apple, 2007)
58. Developmental Interpretation
Brain structure & function in interaction with stress vs. current status of serotonin functioning in the adult brain
(Brown & Harris, 2008)
Epistasis : gene-gene interaction
Individuals may still be resilient event if they posses a risk gene
(Cicchetti et al., 2007)
Supportive relationship with an adult protected maltreated children from developing depression
(Kaufman et al., 2006)
Pharmacological vs. psychosocial
effect on emotion processing in psychiatrically healthy adults
exaggerated amygdala response to fearful or angry faces
(Caspi & Moffitt, 2006; Viding,Williamson, & Hariri, 2006)
Correlation or quasi-experimental designs; no causality
Intervention studies: prediction of treatment efficacy Fernandez
60. Future Directions Absence of psychopathology vs. competent functioning
Effects of genes
(Bakermans-Kranenburg, et al., 2008)
Relationship between breast feeding and IQ scores
(Caspi et al., 2007)
No single allele is risk-inducing under all contexts
(Belsky et al., 2007)
61. Messinger Class Syllabus