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BEHAVIORAL GENETICS

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A quantitative phenotype is influenced by many loci (genes) all ... the relatives' additive, dominance, epistatic, and shared environmental effects,respectively ... – PowerPoint PPT presentation

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Title: BEHAVIORAL GENETICS


1
BEHAVIORAL GENETICS
  • Topic 4
  • Polygenic Model and the Concept of Heritability

2
Single-locus Completely Additive Model
  • Genotype A1A1 A1A2 A2A2
  • Phenotype 71 70 69
  • P G

3
Single-Locus Phenotypic Distribution
A2A2
A2A1
A1A1
69
70
71
4
Two-Locus Phenotypic Distribution
A2A1B2B1
A2A2B2B1
A2A2B1B1
A1A1B2B1
A2A2B2B2
A1A1B1B1
A2A1B2B1
A1A1B2B2
A2A1B1B1
69
70
71
68
72
5
Three-Locus Phenotypic Distribution
69
70
71
68
72
67
73
6
Infinite Number of Loci Model
7
Polygenic Model
  • A quantitative phenotype is influenced by many
    loci (genes) all of which have a small (equal)
    and additive effect.

8
QTL for Open-Field Activity (Flint et al., 1995,
Science 269 1432-5)
17
1
4
15
18
12
Chromosome
9
Polygenic vs. Oligogenic
10
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
11
Biometrical Decomposition
  • P G E (G x E)
  • P G E
  • P (ADI) (EC EW)

12
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

13
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?

14
  • 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

15
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?

16
  • 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

17
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).

18
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?

19
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.

20
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

21
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

22
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

23
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24
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

25
Expected Phenotypic Correlation cor(P1,P2)
rah2N rdd2 rii2 rcc2
26
  • 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

27
Finger Ridge Count Holt (1961)
28
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

29
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30
Genotype-Environment Interaction
  • Genotypes are differentially sensitive to
    environmental influence

31
Cadoret et al. (1995)
32
Diathesis-Stress Model
  • Individuals may inherit a vulnerability
    (diathesis) to psychopathology. Whether that
    vulnerability manifests as psychopathology
    depends on environmental exposure (stress)

33
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.

34
Summary
  • Polygenic Model
  • polygenic vs. oligogenic
  • Biometric decomposition
  • 3 genetic 2 environmental components
  • Heritability
  • Expected familial correlations
  • Genotype-environment interaction correlation
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