BEHAVIORAL GENETICS

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BEHAVIORAL GENETICS

• Topic 4
• Polygenic Model and the Concept of Heritability

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Single-locus Completely Additive Model

• Genotype A1A1 A1A2 A2A2
• Phenotype 71 70 69
• P G

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Single-Locus Phenotypic Distribution
A2A2
A2A1
A1A1
69
70
71
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Two-Locus Phenotypic Distribution
A2A1B2B1
A2A2B2B1
A2A2B1B1
A1A1B2B1
A2A2B2B2
A1A1B1B1
A2A1B2B1
A1A1B2B2
A2A1B1B1
69
70
71
68
72
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Three-Locus Phenotypic Distribution
69
70
71
68
72
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73
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Infinite Number of Loci Model
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Polygenic Model

• A quantitative phenotype is influenced by many
  loci (genes) all of which have a small (equal)
  and additive effect.

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QTL for Open-Field Activity(Flint et al., 1995,
Science 269 1432-5)
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4
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Chromosome
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Polygenic vs. Oligogenic
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Polygenic/Oligogenic Model
Mendelian Modes of Inheritance
Biometric Model
Inference on mode of inheritance
Mendels Laws
Heritability
Patterns of Familial Resemblance
Patterns of Familial Resemblance
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Biometrical Decomposition

• P G E (G x E)
• P G E
• P (ADI) (EC EW)

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Genetic Components

• A Additive genetic component, effect of genes
  taken singly summed over loci.
• D Dominance genetic effects, effects due to
  interaction of alleles at a given locus summed
  over loci
• I Epistasis, genetic effects due to
  interactions across loci

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Additive vs. Dominance Effects

• Completely additive model
• A1A1 A1A2 A2A2
• 71 70 69
• If father is heterozygote, A1A2, what is the
  effect of his passing on the A1rather than the A2
  allele to a child?

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• Mother Contributes an A1
• Father contributes A1 ? A1A1 ? 71
• ?
• Father contributes A2 ? A2A1 ? 70
• Mother Contributes an A2
• Father contributes A2 ? A2A1 ? 70
• ?
• Father contributes A2 ? A2A2 ? 69

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Additive vs. Dominance Effects

• Non-additive model
• A1A1 A1A2 A2A2
• 71 70.5 69
• If father is heterozygote, A1A2, what is the
  effect of his passing on the A1rather than the A2
  allele to his child?

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• Mother Contributes an A1
• Father contributes A1 ? A1A1 ? 71
• ?
• Father contributes A2 ? A2A1 ? 70.5
• Mother Contributes an A2
• Father contributes A1 ? A2A1 ? 70.5
• ?
• Father contributes A2 ? A2A2 ? 69

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Polygenic Dominance

• The effect of an allele at a locus depends on the
  allele it is paired with at that locus (i.e., the
  contribution of the other parent).

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Epistasis

• Suppose that to develop some disease (or be
  extreme on some quantitative dimension) an
  individual needed to inherit A1, B1, C1, D1 and
  E1 at 5 separate loci. If an individual is
  affected, how likely is it that
• They have an affected parent?
• They have an affected sibling?
• They have an affected monozygotic twin?

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Environmental Components

• EC Family environmental effects that
  differentiate one family from another. Usually
  called Shared Environmental or E2 effects.
• EW Environmental effects that differentiate one
  family member from another within a family.
  Usually called Nonshared Environmental E1 effects.

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Decomposition of Variance

• VP VG VE
• VP (VAVDVI) (VECVEW)
• VP/ VP (VA / VP VD / VP VI / VP ) (VEC / VP
  VEW / VP )
• 1.0 a2 d2 i2
  c2 e2

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Heritability

• Statistical Definition
• Narrow Heritability
• h2N a2 VA / VP
• Broad Heritability
• h2B (VAVDVI)/ VP
• Conceptual Definition
• Proportion of phenotypic variance associated with
  (i.e., predictable from) genetic factors

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Properties of Heritability

• Measures extent to which current G E
  differences among individuals predict their
  phenotypic differences
• Not an index of malleability
• It is a population statistic
• Not a biological constant
• Does not specify underlying mechanism

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Familial Resemblance

• cor(P1,P2) rah2N rdd2 rii2 rcc2
• where ra, rd, ri, rc are, the correlations in the
  relatives additive, dominance, epistatic, and
  shared environmental effects,respectively

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Expected Phenotypic Correlationcor(P1,P2)
rah2N rdd2 rii2 rcc2
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• ra probability two relatives share a randomly
  selected allele at a randomly selected locus
  identical by descent (IBD)
• (1/2)n , n degree of relationship
• rd probability two relatives share a both
  alleles at a randomly selected locus IBD
• ri indeterminate, but depends on probability
  two relatives share alleles across loci IBD
• rc usually specified as 1.0 for
  reared-together relatives

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Finger Ridge CountHolt (1961)
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Biometric Analysis of Familial Correlations

• Although in principle 5 sources of variance are
  estimable (a2, d2, i2, c2 e2), in practice
  usually only 3 are estimated (a2, c2 e2)
• Estimates of a2, c2 e2 are used to gain an
  approximate sense of the major sources of
  phenotypic variance

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Genotype-Environment Interaction

• Genotypes are differentially sensitive to
  environmental influence

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Cadoret et al. (1995)
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Diathesis-Stress Model

• Individuals may inherit a vulnerability
  (diathesis) to psychopathology. Whether that
  vulnerability manifests as psychopathology
  depends on environmental exposure (stress)

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Genotype-Environment Correlation

• Passive - arises because parents provide both the
  genes and the environment of their children.
• Evocative (Reactive) - arises because an
  individuals social environment is in part of
  function of how others react to his/her behavior.
• Active - arises because an individuals
  environment is in part a function of his/her
  choices.

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Summary

• Polygenic Model
• polygenic vs. oligogenic
• Biometric decomposition
• 3 genetic 2 environmental components
• Heritability
• Expected familial correlations
• Genotype-environment interaction correlation