Genetics and Prenatal Development

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. Rutter, M. (2002). Nature, nurture, and development: From evangelism through science towards policy and practice. Child Development, 73, 1-21. dg. Messinger. Nature: Genetic Risk and Protective Factors. Quantitative genetics:Quantifies the strength of genetic and non-genetic factorsHave increasingly been finding interplay between genetic and non-genetic factorsGenetics believed to play role in all traits, with non-genetic influences also important
Genetics and Prenatal Development

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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) Molecular genetics: 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 Nurture ? environment Infinite malleability Genes, environment, and their interaction accounting for outcome? Gene-environment transaction?

8. Messinger Some basics Genes Bits of DNA, protein, in each cell contain information on cell functioning, production, and reproduction Chromosomes 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 Observable trait ?Phenotyping? The broader phenotype (autism) Genotype 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 Reaction Range 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-like modes 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 Non-sex chromosomes One pair from each parent When 2 competing traits are inherited Only 1 trait is expressed Dominant trait Recessive trait

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 Male?s ?x? inherited from mother Women are carriers Males represented disproportionately in sex linked disorders Color-blindness, hemophilia

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 genetic duplicates. Fraternal (DZ) twins share 50% of their genes on average 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.

31. Messinger

32. Messinger Sources of Variance in Behavior Genetic (heritability) Environmental Gene x environment interaction Error

33. Messinger Estimates of genetic and environmental influence Proportional in samples Greater environmental variation Will minimize genetic variation E.g. Poverty 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? How?

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 of?G*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

45. Gene-environment interactions (G x E) Environmental risks that interact with genes to predict vulnerability and resilience Fernandez

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) Fernandez

47. Messinger

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. Methylation 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 Mattson

52. Epigenetics in Rodents Champagne?s 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) Fernandez

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) Relationship Effect Supportive relationship with an adult protected maltreated children from developing depression (Kaufman et al., 2006) Fernandez

59. Interventions Pharmacological vs. psychosocial ? Imaging genomics? effect on emotion processing in psychiatrically healthy adults exaggerated amygdala response to fearful or angry faces (Caspi & Moffitt, 2006; Viding,Williamson, & Hariri, 2006) Limitations 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 Supportive caregiving (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) Fernandez

61. Messinger Class Syllabus

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