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BEHAVIORAL GENETICS

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A quantitative phenotype is influenced by many loci (genes) all of which have a ... (Flint et al., 1995, Science 269: 1432-5) 1. 4. 15. 18. 12. 17. Chromosome ... – PowerPoint PPT presentation

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Title: BEHAVIORAL GENETICS


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

2
Quantitative Phenotypes
3
Single-locus Completely Additive Model
  • Genotype A1A1 A1A2 A2A2
  • Phenotype 71 70 69
  • P G

4
Single-Locus Phenotypic Distribution
A2A2
A2A1
A1A1
69
70
71
5
Two-Locus Phenotypic Distribution
A2A1B2B1
A2A2B2B1
A2A2B1B1
A1A1B2B1
A2A2B2B2
A1A1B1B1
A2A1B2B1
A1A1B2B2
A2A1B1B1
69
70
71
68
72
6
Three-Locus Phenotypic Distribution
69
70
71
68
72
67
73
7
Infinite Number of Loci Model
8
Polygenic Model
  • A quantitative phenotype is influenced by many
    loci (genes) all of which have a small (equal)
    and additive effect.

9
Open-Field Activity
10
QTL for Open-Field Activity (Flint et al., 1995,
Science 269 1432-5)
17
1
4
15
18
12
Chromosome
11
Height Polygenic or Oligogenic?
Average Effect of Replicated Genetic Variant
.2-.3 of variance or 0.4cm
12
Polygenic vs. Oligogenic
13
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
14
Biometrical Decomposition
  • P G E (G x E)
  • P G E
  • P (ADI) (C E)

15
Biometric Components
16
Decomposition of Variance
  • VP VG VE
  • VP (VAVDVI) (VCVE)
  • VP/ VP (VA / VP VD / VP VI / VP ) (VC / VP
    VE / VP )
  • 1.0 a2 d2 i2
    c2 e2

17
Heritability
  • Narrow-sense heritability
  • a2 VA/VP
  • Proportion of phenotypic
  • variance predictable from additive
    genetic effects
  • Broad-sense heritability
  • h2 (VA VD VI )/VP
  • Proportion of phenotypic
  • variance predictable from all genetic
    effects

18
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

19
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20
Polygenic/Oligogenic Model
Biometric Model
Heritability
Patterns of Familial Resemblance
21
Familial Resemblance
  • cor(P1,P2) raa2 rdd2 rii2 rcc2
  • where ra, rd, ri, rc are, the correlations in the
    relatives additive, dominance, epistatic, and
    shared environmental effects, respectively

22
Expected Phenotypic Correlation cor(P1,P2) raa2
rdd2 rii2 rcc2
23
  • 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

24
Finger Ridge Count Holt (1961)
25
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

26
Genotype-Environment Interaction
  • Genotypes are differentially sensitive to
    environmental influence

Cadoret et al. (1995)
27
Diathesis-Stress Model
  • Individuals may inherit a vulnerability
    (diathesis) to psychopathology. Whether that
    vulnerability manifests as psychopathology
    depends on environmental exposure (stress)

28
APOE e4 and Boxing
APOE e4 and Dementia
Mayeux, R. et al. (1995). Neurology, 45 555-557.
Jordan, B.D. et al. (1997). JAMA, 278 136-140.
29
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.
30
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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