DNA and Gene Expression

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Transcript DNA and Gene Expression

General and Specific Cognitive
Abilities
Cognitive Abilities
• Specific cognitive abilities
– E.g., verbal ability, spatial ability, memory,
speed of processing
• General cognitive ability (g)
– Often used to be called “intelligence”
Hierarchical Models
• Very prevalent in cognitive sciences
• Work on the premise of interconnected
levels
• Different “units” in each level
– Specific units might interconnect within and
between levels
Hierarchy of Cognitive Ability
General cognitive
ability (g)
Specific cognitive
ability
Individual tests
Interactions
• Hundreds of individual psychological tests
used in assessment
• Moderate correlation between performance
on different specific cognitive abilities
– E.g., do well on spatial, probably do well on
memory
Correlations
• Not empirical; correlation is not causation
• Correlations can not tell why/how one
factor relates to another, just the degree to
which they do (or do not)
Genetic Regulation
• Not really much question that there is
heritability involved in cognitive ability
• Specific gene and environmental control,
however, is still pretty much unknown in
humans
• Better understanding in nonhumans
– Empirical testing can be conducted
Intelligence Testing
• Various intelligence (IQ) tests
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Alfred Binet
Identify students needing special help
First test, 1905
Revised to Binet-Simon (1908, 1911), then
Stanford-Binet (1916)
Studies in Human Intelligence
• Early adoption studies (Burks 1928; Leahy 1935)
– IQ correlates higher in nonadoptive families than in
adoptive families
• Adopted away children’s IQ correlates with their
biological parents (Skodak & Skeels 1949)
– This is increasingly true as child ages
• 1960 Louisville Twin Study, longitudinal study of
environment and genetic effects begun
Heritability and Intelligence
Correlations
• First degree relatives, ~0.45
• Adopted away children and biological
parents, ~0.25
• Sibs adopted apart, ~0.25
• MZ, ~0.85
• DZ, ~0.6
• MZ raised apart, ~0.75
Couple Complications to This…
• Assortative mating
• Nonadditive genetic variance
Assortative Mating
• Non-random mating; when mates have similar
features/characteristics
• Important for our discussion
• Affects estimates of heritability
• In first-degree relatives can inflate heritability
– E.g., sibs are more similar in trait because parents are
similar for same trait
• In twins, though, can underestimate heritability
– Raises DZ correlations because they’re 1st degree
relatives, so lessens difference b/t MZ and DZ twins
Nonadditive Genetic Variance
• Additive genetic effects
– Alleles at locus and across loci “add up”
• Nonadditive effects
– Effects of alleles different in presence of other alleles
• Dominance
– Alleles at same locus interact
– E.g., heterozygous phenotype different from homozygous dominant
phenotype
• Epistasis
– Alleles at different loci interact to affect behaviour; phenotype of
different genes suppressed or expressed
• Emergenesis
– Epistatic effects producing extraordinary effects; won’t be heritable
due to interactive nature
General Intelligence
• Charles Spearman
– Schoolchildren’s grades across unrelated subjects
positively correlated
– Proposed “general” intelligence
– Initial interpretation that variation in intelligence due to:
– Factor specific to an individual mental task
– A general factor, g, that governs performance on all
cognitive tasks
• Ignored group factors, however… need factor
analysis to identify this
g-Factor
• Is g real?
• What is the actual interaction between
specific and general cognition?
• Correlations
g-Loading
• Tests of cognitive ability derive most of
their validity from the extent to which they
measure g
• g-loaded if quantifiable measure(s) of a task
correlate highly with g
• Primary goal of IQ tests is to create reliable
and valid tests; thus, the tests tend to be
intentionally g-loaded
Non-specificity
• However, g not specific to any particular
domain of knowledge or mental skill
• Also, seems independent of cultural content
• Support idea that g is real and not simply an
artifact of particular opportunities to learn
specific “skill sets”
Biological Correlates
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Brain size correlate with g, ~0.4
Various brain wave activity and g, 0.5-0.7
Speed of nerve conduction with g, ~0.4
Even elementary cognitive tasks (ECTs)
correlate with g (tasks like identify the
colour of a light, number of figures on a
page, etc.)
g
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g widely accepted
Seems to have moderate to high heritability
That said, less clear what g really is
Single general process?
– E.g., information processing speed, executive function
• Interaction/intersection of specific cognitive
functions?
• Frequently, g used synonymously with
“intelligence”
QTL and g
• Highly likely that many separate
components contribute
– Polygenic
– Environment
• Effect at what level?
– Elementary properties, specific cognitive
ability, general cognitive ability
Top down
• Genes act directly on g
– E.g., perhaps through neural activity speed, etc.
General cognitive ability
Specific cognitive abilities
Elementary processes
Genes
Bottom Up
• Genes affect each basic element of
information processing
– Highly reductionistic model
General cognitive ability
Specific cognitive abilities
Elementary processes
Genes
Multi-level Interaction
• Unique genetic effects at each level, but
also genetic effects in common across levels
General cognitive ability
Genes
Specific cognitive abilities
Genes
Elementary processes
Genes
Evidence
• Some support for top down
• Modularized view of brain function would
fit well with bottom up
• However, multivariate genetic analysis
supports multi-level interaction
– Keep in mind, this model incorporates elements
from both top down and bottom up
Non-human Animal Models
• Can look for g-like abilities in non-humans
• Look for specific cognitive abilities that are
directly comparable across species (e.g.,
spatial ability)
Maze Dull/Maze Bright
Mean Errors
• Tolman and Tyron
• Selectively bred rats for ability in maze
learning
• Maze bright rats showed few errors, maze
dull rats many errors after few generations
Maze dull
20
Maze bright
0
1
Generations
22
Heritability for Learning
• Inbred strains of mice
Bovet et al. (1969)
Heritability in Learning
Bovet et al. (1969)
• In and of itself, not that novel, unexpected,
surprising
• But, environmental effects can come in…
Genotype-Environment Interaction
• Cooper & Zubek (1958)
• Enriched, restricted,
standard lab conditions
• Enriched improves MD,
not MB
• Restricted detrimental to
MB, not MD
Popularity of Mice
• Mouse genome
• Can test for specific gene effects
– E.g., transgenic critters
• Very useful for genotype-environment
interactions with respect to cognitive
abilities
• Obviously, more difficult in humans, but
starting to get there
Caspi et al. (2007)
• Children’s intellectual development
• Interaction of genetic and environmental
experience
• Breastfeeding
• IQ scores
Breastfeeding
• Long-chain polyunsaturated fatty acids (LCPUFAs)
– Present in human milk, absent in cow’s milk
– Specifically, DHA (docosahexaenoic acid) and ARA
(arachidonic acid)
– Required for efficient neurotransmission, neurite
outgrowth, dendritic arborization, and neuron
regeneration post cell injury
• DHA and ARA accumulate in human brain in
early postnatal months
– Higher concentrations in breastfed than formula fed
infants
Effect on IQ
• Breastfed children have higher IQs than
non-breastfed children
– Effect persists into adulthood
• Not due to SES or other culture-specific
factors
– Important to control for, as in Western
countries, higher SES is related to higher IQ,
and higher SES women are more likely to
breastfeed
Non-human Animal Models
• Animals deprived in n-3 fatty acids show
neuronal deficits in memory, sensory, and
visual abilities
• DHA supplementation in rodents and
nonhuman primates increases DHA
concentrations; enhances performance on
learning, memory, and problem solving
tasks
FADS2
• Chromosome 11 candidate gene
• Role in modification of dietary fatty acids
• Encodes delta-6 desaturase, the rate limiting step
on the metabolic pathway for ARA and DHA
production
• Hypothesis: cognitive advantage of breastfeeding
related to genetic differences in LC-PUFA
metabolism, specifically at FADS2
Markers and Subjects
• Used two SNPs
– Genetic polymorphisms rs174575 and rs1535
– Strong linkage disequilibrium through promoter and
intragenic region of FADS2 (and also FADS1, another
gene involved in fatty acid metabolism)
• Over 1000 New Zealand children born 1972-73,
IQ measures at age 7, 9, 11, 13
• Over 2200 children from British twins born 199495; IQ measured at age 5
IQ Outcomes and Genotype
110
105
New Zealand
Cohort
British
Cohort
100
95
90
CC
CG
GG
CC
Genotypes
Not breastfed
CG
GG
Breastfed
Overall, breastfed children had IQ scores 5.6 and 6.3 points higher than
non-breastfed children in New Zealand and British cohorts, respectively.
About 90% either CC or CG.
Genotype and IQ
• Dominant effect of C allele in response to breastfeeding
• New Zealand: breastfed children with C allele showed 6.4
IQ-point advantage (p<0.001) compared to non-breastfed
children; GG homozygotes gained no advantage from
breastfeeding
• British: breastfed children with C allele showed 7.0 IQpoint advantage (p<0.001); GG had no advantage from
breastfeeding
• Averaging, this equates to a 6.8 IQ point advantage, or
0.48 standard deviation units in the general population
rs174575
• Genetic moderation of breastfeeding effects
on IQ not likely directly due to rs174575
– Actual molecular mechanism of influence by
rs174575 is currently unknown
• May be that rs174575 influences
biosynthesis of LC-PUFAs from dietary
precursors, possibly through increased
transcriptional activity
Application
• Earlier studies looking at neurodevelopment
of infants fed DHA-supplemented vs.
unsupplemented formula
– Results inconclusive
– Current research may offer explanation; genetic
heterogeneity in fatty acid metabolism may
dilute supplemental effects
Application
• FADS2 locus has not appeared on the first
genome-wide scans for intelligence
• Such scans identify genes with associations with
phenotypes regardless of participants’
environments; ineffective for detecting genes
whose effects are conditional on environmental
exposure
• In contemporary Western samples, significant
portion of population is not breastfed; this would
conceal link between FADS2 variation and IQ
Heritability and Maturation
• Early twin studies investigated development
(e.g., Galton, 1876; Merriman, 1924)
• Heredity increasingly important as you
develop
Developing Twins
Why
• New genes come into effect
• Positive feedback effect
– IQ increase when adopted by parents with high IQ
• Intellectual experience more self-directed as an adult
• Shared environment effects decrease with age
Genetic Contributions to
Developmental Change
• g is pretty stable, not perfectly so… if change happens, it has
a genetic aspect
• Genetic effects seem to act at transitional ages
– Infancy to early childhood (e.g., language acquisition)
– Early to middle childhood (e.g., theory of mind)
– Etc.
Gen. factors
New gen. factors
New gen. factors
Infancy
Early childhood
Middle childhood
Shared Env.
Environment & Specific Cognition
• Scarr & Weinberg (1978)
• Adoption study
• Little similarity for adoptive parents and adopted
children or between adopted siblings on specific
subsets of intelligence test… except vocabulary
• Like g, specific cognitive abilities also little
influenced by shared environment (i.e., heritability
significant factor)
Academic Performance
• Achievement vs. ability
– Semantics?
• Shared environment ~60%, heritability
~30% (for 6-12 year range)
• Heritability effect does increase, and
environment effect decreases with age
Heritability and Subjects
From Grade 7 Report Card Grades
From High School Achievement Tests
Twin Correlations
Subject
MZ
DZ
History
.80
.51
Reading
.72
.57
Writing
.76
.50
Arithmetic .81
.48
Twin Correlations
Subject
MZ
DZ
Social
.69
.52
Natural Sciences .64
.45
English use
.72
.52
Mathematics
.71
.51
School Achievement = g?
• Multivariate genetic analysis shows a common
genetic effect explains much of the correlation
between scores in different domains (i.e., subjects)
• Is this g, or some other measure?
– Some-to-much of this is g, but some is achievement
specific
• Implies that achievement scores (within normal
range) that are not due to ability are largely due to
environment
Overall
• Variance in thirds
• One third of genetic variance of academic
performance is in common with general cognitive
ability
• One third of genetic variance is general to
academic performance, independent of general
cognitive ability
• One third is specific to each domain
• Means learning abilities are not exactly the same
thing genetically as general cognitive ability