DNA and Gene Expression

Download Report

Transcript DNA and Gene Expression

General and Specific Cognitive
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
• Different “units” in each level
– Specific units might interconnect within and
between levels
Hierarchy of Cognitive Ability
General cognitive
ability (g)
Specific cognitive
Individual tests
• 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
• 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
• Better understanding in nonhumans
– Empirical testing can be conducted
Intelligence Testing
• Various intelligence (IQ) tests
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
• 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
• 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
• 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
• Is g real?
• What is the actual interaction between
specific and general cognition?
• Correlations
• 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
• 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
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 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
• Frequently, g used synonymously with
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
Bottom Up
• Genes affect each basic element of
information processing
– Highly reductionistic model
General cognitive ability
Specific cognitive abilities
Elementary processes
Multi-level Interaction
• Unique genetic effects at each level, but
also genetic effects in common across levels
General cognitive ability
Specific cognitive abilities
Elementary processes
• 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
• Maze bright rats showed few errors, maze
dull rats many errors after few generations
Maze dull
Maze bright
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,
• 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
• Obviously, more difficult in humans, but
starting to get there
Caspi et al. (2007)
• Children’s intellectual development
• Interaction of genetic and environmental
• Breastfeeding
• IQ scores
• 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
Effect on IQ
• Breastfed children have higher IQs than
non-breastfed children
– Effect persists into adulthood
• Not due to SES or other culture-specific
– Important to control for, as in Western
countries, higher SES is related to higher IQ,
and higher SES women are more likely to
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
• 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
• 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
New Zealand
Not 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
• British: breastfed children with C allele showed 7.0 IQpoint advantage (p<0.001); GG had no advantage from
• Averaging, this equates to a 6.8 IQ point advantage, or
0.48 standard deviation units in the general population
• 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
• 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
• 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
• 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
Developing Twins
• 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
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
Arithmetic .81
Twin Correlations
Natural Sciences .64
English use
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
• Implies that achievement scores (within normal
range) that are not due to ability are largely due to
• Variance in thirds
• One third of genetic variance of academic
performance is in common with general cognitive
• 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