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Genetics and Prenatal Development

D. Messinger, Ph.D.

Psychology of Infancy

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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?

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Nature – genetics– Genes as blueprint

Nurture – environment– Infinite malleability

Genes, environment, and their interaction accounting for outcome?

Gene-environment transaction?

Back to developmental models Who believes in?

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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

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Chromosomes

In vitro Ordered by karotyping

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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

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Detailed description

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Genomes to Life Project - Proteomics

Identify the protein machines that carry out critical life functions and the gene regulatory networks that control these machines

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Terms

Phenotype– Observable trait

“Phenotyping” The broader phenotype (autism)

Genotype– Genetic pattern associated with the phenotype

The ‘broad’ phenotype?

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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

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Blueprint-likemodes of genetic transmission Dominant-recessive

– Single gene or Mendellian Specific genetic defects can be deadly or disabling http://www.uaf.edu/psych/psyc240/exam1/index.html, Jim Allen, Ph.D

– Phenylkitenuria, sickle cell, etc.

Sex-linked (23rd chromosome)

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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

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Dominant-Recessive Inheritance

Norm al(NN )

Carrier(Nr)

Carrier(Nr)

Affected(rr)

Carrier Father (Nr)+

Carrier M other (Nr)

Traits are transmitted as separate units •25% risk of inheriting a “double-dose” of r genes

•which may cause a serious birth defect•25% chance of inheriting two N’s

•thus being unaffected•50% chance of being a carrier as both parents are

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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

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Sex-linked inheritance

Male’s “x” inherited from mother– Women are carriers– Males represented disproportionately in sex linked

disorders baldness color-blindness, hemophilia

– Baldness: maternal gf > f

Even sex-linked characteristics are dependent on environmental influences– Expression of baldness depends on circulating

testosterone levels

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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)

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Behavioral genetics

Measuring genetic and environmental influences on behavior

Finding genes for behaviors?

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Twin Studies

Monozygotic vs Dizygotic: human studies ofgenetic versus environment

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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

• http://www.psych.umn.edu/psylabs/mtfs/special.htm

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No genetic influence

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50% Dizygotic 100% - Monozygotic

Genetic Relatedness

Twin 1Twin 2

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Complete genetic influence

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Genetic Relatedness

Twin 1Twin 2

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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.

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Sources of Variance in Behavior

Genetic (heritability) Environmental Gene x environment interaction Error

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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

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Questions

Why might adoption studies maximize estimates of genetic influence?

Can genetic effects increase with time?– How?

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Gene*Environment Interaction

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Transactional perspective on gene*environment interface “It is not nature vs. nurture, but the

interaction of nature and nurture that drives development.” Urie Bronfrenbrenner (what we just heard)

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“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.

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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?

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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?

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Gottlieb, 2003Gene * environment interactions

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Reaction range: Genetic constraints on environmental variability

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Transactional model

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Demonstrates importance of…

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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

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Champagne & Mashoodh (2009) Author's Perspective

Interactions between genetics and environment should be examined as we move past nature and nurture.

"To move forward, we must ask 'What do genes do?’ and ‘How do genes and environments interact?’" (127)

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 Methylation can mask the transcription of certain genes sites based on

cell conditions. Could lead to a particular gene not being expressed.

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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.

Miller and Sweatt (2007)- Inhibition of methylation also has detrimental effects on memory

In addition to stress effects during pregnancy, rodents place on methyl rich diets can cause an effect in color expression with the Agouti mutation.

In Champagne's earlier studies (2006, 2007) epigenetic effects can be passed down to later generations.

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What Can Methylation Mean for Humans?

A study of methylation of fetal cord blood by Oberlander (2008) indicates stress response effects at three years of age.

Mirrored in methylation levels of suicide victims in a study by McGowan (2008).

Twin studies, particularly Fraga's (2005), indicate genetic variation between young and old monozygotic twins. Champagne and Mashoodh suggest this could account for differential diagnosis.

Need for additional study of lasting epigenetic effects in humans.

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True or false?

Inherited DNA determines gene expression through the lifespan

Environmental factors for generation 1 can influence gene expression in generation 2

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Measured Gene-Environment Interactions and Mechanisms Promoting Resilient Development .

(Julia Kim-Cohen & Andrea L. Gold, 2009)

Veronica FernandezPsy 641

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Childhood maltreatment increases risk for later mental and physical health problems

Resilience promotes positive adaptation despite exposure to adverse life experiences

Gene-environment interactions (G x E) Environmental risks that interact with genes to

predict vulnerability and resilience

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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)

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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)

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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)

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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

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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)

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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?

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Prenatal development is usually divided into three main periods. Zygote -

– covers the first two weeks after conception– ends when the zygote implants into the wall of the mother's

uterus.

Embryo - – from two to eight weeks following conception– the major organs and bodily systems form

Fetus– from eight weeks after conception until birth – grows tremendously in size and weight.

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Zygotic cell differentiation

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From zygote to embryo

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The question

The zygote grows through cell division– Mitosis - One for one copying of all 23

chromosomes All cells contain the same genetic

information in their nuclei But qualitatively different types of cells

develop in different parts of the body How does this occur?

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General processes yield specific outcomes Cells clump together as a sphere This changes the extra-cellular environment

of cells on the inside and outside of the sphere

Differences in environment impact cell’s genetic make-up to activate different proteins

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Genes in Environment

Environmental factors influence development from the start– Cells are environments– The uterus is an environment

The fetus participates in actively constructing its own development– it is not passively constructed

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Creation of a tube

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Embryology

Cells groups in which specific molecular processes occur with boundaries with other groups

Regulator genes activate and de-activate other genes within these groups

Cells impact each other such that a nerve cell transplanted to the liver region becomes a liver cell after several replications

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What do you think?

Stem cell debate Cloning Assistive reproduction technology

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Additional readings

Plomin, et al. The genetic basis of complex human behaviors. Plomin, R., & Rutter, M. (1998). Child development, molecular

genetics, and what to do with genes once they are found. Child Development, 69(4), 1223-1242.

Rutter. M. (in press [2002]. Nature, nurture, and development: From evangelism through science towards policy and practice. Child Development.

Collins, W. A., Maccoby, E. E., Steinberg, L., Hetherington, E. M., & Bornstein, M. H. (2000). Contemporary research on parenting: The case for nature and nurture. American Psychologist, 55(2), 218-232.

Sleigh, M. J., Columbus, R. F., & Lickliter, R. (1998). Intersensory experience and early perceptual development: Postnatal experience with multimodal maternal cues affects intersensory responsiveness in Bobwhite Quail Chicks. Developmental Psychology, 34(2), 215-223.

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