Wk3 Cognitive Genetics Flashcards
1
Q
what do genes basically do?
A
code for a protein product
2
Q
what could be the consequences of slight variation in protein expression?
A
alterations in brain function and structure between people
3
Q
what is the basic idea/model of how cognitive genetics works?
A
genetic variation -> protein expression -> brain (structure/function) -> cognition
genes affect cognition through the above pathway
4
Q
what is a genotype?
A
variation in genes across people
5
Q
what is the aim of cognitive genetics?
A
linking genetic variation to variation in cognitive abilities
6
Q
what are three ways to investigate genotypes?
A
twin studies
candidate genes
genome wide association
7
Q
def complex trait. what influences it? 3
A
a quantifiable property of an organism
influenced by
- multiple genes
- enviornmental factors
- interactions between them
8
Q
phenotype?
A
physical appearance of an organism with respect to a trait
how a complex trait manifests
9
Q
endophenotype?
A
measurable components that lie along the causal pathway between disease (phenotype) and distal genotype
10
Q
why examine an endophenotype?
A
can be hard to examine the full expression of a phenotype. e.g. complex clinical diagnoses are required for ADHD vs easier to look at sustained attention as an aspect of the full trait
11
Q
what is an advantage to investigating an endophenotype? consequence?
A
simpler and easier to measure (than a complex trait) ,
so possibly controlled by fewer genes.
12
Q
what makes up the genome?
A
23 pairs of chromosomes, in each pair one comes from each parent
13
Q
what is a gene?
A
length of DNA that specifies a particular protein product
14
Q
what is an allele?
A
one of two or more forms of a gene (different versions of the same gene)
15
Q
what does homozygous mean?
A
the same alleles on both chromosomes (mother and father)
16
Q
what does heterozygous mean?
A
different alleles (forms of the same gene) at each chromosome
17
Q
if you got different alleles from your mother and father this gene is ___
A
heterozygous
18
Q
what are two common types of genetic variation?
A
single nucleotide polymorphisms (SNP)
variable number of tandem repeats (VNTR)
19
Q
what is a single nucleotide polymorphism?
A
when alleles differ at a single base pair (or one location)
20
Q
if AAGCCTA differs from AAGCTTA, this is a ___
A
single nucleotide polymorphism
21
Q
what is a VNTR?
A
a location in a genome where a short nucleotide is organised as a tandem repeat of a particular (variable length, 10 -100)
22
Q
how are individuals classified using VNTR?
A
based on how many copies of the repeat length of interest they have: 0, 1, or 2.
23
Q
what is a polymorphism?
A
the presence of two or more variants (alleles) in a gene or DNA sequence in a population
24
Q
what are the most common polymorphisms?
A
SNPs
25
what does a SNP reflect?
a change in a single base in the DNA that differs from the usual base at that position
26
a polymorphism in the length of tandemly repeated short sequences of DNA is called ___
VNTR
27
2 phenotypical aspects of ADHD required for diagnosis
inattention
| hyperactivity/impulsivity
28
what would be an endophenotype in ADHD?
sustained attention
29
def sustained attention
ability to maintain goal-directed focus in the absence of exogenous or external cues
30
what task can test sustained attention? how does it measure it?
SART: sustained attention to reaction time
| behaviourally
31
what does a SART task involve?
press or don't press a button, in response to a cue presented earlier
32
what is an advantage of heritability/twin studies?
they can measure both genetics and environment and compare their interaction
33
what is a disadvantage of heritability/twin studies?
they can't specify which genes, only that genes are important
34
what are the 3 influences in a twin study model?
additive genetic influences
shared environmental influences
non-shared environmental influences
35
what could you conclude if MZ twins have low correlation on an ability/trait? why?
differences are due to non-shared environments
| MZ twins share genes and environment
36
what could you conclude if there are high correlations of a trait/ability in both MZ and DZ twins? why?
effects are due to shared environment
| differences in % of shared genes between DZ & MZ did not produce an influence
37
what could you conclude if there are high correlations in a trait/ability for MZ twins, but low correlations for DZ twins? Why?
effects are due to genetics
| 100% shared genes in MZ twins is the only extra factor that could account for increased twin similarity
38
heritability estimate for ADHD?
60-90%
39
describe the dose effect of genes on ADHD
unaffected siblings perform better on sustained attention but worse than healthy controls
40
heritability estimates for sustained attention change ___ . how?
with age
| less influence the older you get
41
heritability estimate for sustained attention in children
46-72%
42
what was the biggest driver of classroom behaviour in children from wales vs london (davis et al) ? where was this found?
non-shared environment
| biggest in london but differed across UK
43
what did Davis et al conclude about heritability of classroom behaviour across UK? what was their geocoding evidence ?
diverse environments give more possibility for non-shared environmental influence
london had the greatest variance in household income AND the greatest influence of non-shared environment on behaviour
44
what did a huge geocoding survey (Davis et al) find about ADHD expression and genes? what was their conclusion?
genes had a bigger influence on ADHD in london
| some aspect of the environment is necessary to allow gene's to express a phenotype
45
why is it not enough to have a gene that is capable of expressing a phenotype? (eg?)
genes may not show the phenotype if there is not an environment to display it in
eg: you may have a gene for allergies, but never have hayfever if you don't live next to a field
46
what was the Scarr-Row hypothesis about nature/nurture interactions for IQ?
genes > environment influence for advantaged groups compared to disadvantaged groups
47
in Davis et al twin study on ADHD in UK: twins were aged __ when tested. each pair was __ based on __
12
geocoded
postcode
48
in Davis et al twin study on ADHD in UK: 45 phenotypes were investigated including ___ 3
IQ
ADHD
school achievement
49
Why is the influence of poverty on IQ dependent on country/culture?
low SES people have different access to basic needs in richer vs poorer countries
50
where was a gene x SES interaction found to occur?
only in the US
51
what is the biggest determinant of IQ for low SES vs high SES americans?
low SES: environment > heritability
| high SES: genes > environment
52
def heritability and how it is estimated
proportion of variance explained by genetic factors for a certain phenotype
concordance rates of MZ and DZ twins
53
def gene x environment interactions
when relationships between experience and altered behaviour/physiology is moderated by individual differences in genes (ie. polymorphisms)
54
candidate gene studies involve a ____ selection of specific genes
theory driven
55
what do candidate gene studies investigate?
how the candidate gene influences individual differences in a specific cognitive process
56
how many possible versions of a SNP could people in a population have?
3
eg c/t, t/t, c/c alleles
57
what is the selction of a candidate gene based on? 4
pharmacology
brain imaging
animal research
behavioural studies
58
what NT system is important for ADHD candidate gene selection?
dopamine
59
sustained attention brain network overlaps with
the network for the dopamine system
60
experimental depletion of dopamine leads to
sustained attention deficits
61
what is the most commonly used medication for ADHD? is effective in __ of cases.
methylphenidate (MPH)
| 60%
62
clinical benefit of MPH is often attributed to action on __
blockade of the dopamine transporter (DAT)
63
MPH significantly improves sustained attention deficits in children and adults but only for ___
those with ADHD
64
where is the dopamine transporter protein DAT1 found?
caudate nucleus
65
MPH makes dopamine have a stronger effect in the brain how?
stops DAT1 from clearing away DA (inhibiting uptake)
66
what is the most commonly studied variant of DAT1 genes? the most frequent allele has how many variable repeats?
a VNTR in the 3'UTR (intron)
| 10 or 9
67
Ps with one copy of the 10-repeat dopamine transporter allele (10/10 or 9/10) have ____ compared to ___
higher dopamine transport density
| 9/9 carriers
68
children with ADHD that are homozygous for the 10 repeat DAT1 allele perform ___ than ___
more poorly on sustained attention tasks
| children with other genotypes
69
MPH makes dopamine act __
for longer
70
what is a conclusion about one genetic effect and mechanism of ADHD?
selective attention is impaired because DAT1 (uptake protein) produces low persistence of DA
71
what function describes the effect of Dopamine on task performance?
inverted-U
72
what types of cognitive impairment might be found at the extremes of dopamine levels?
too little: inattention & drowsiness
| too much: anxiety & dysphoric psychosis
73
DRD4 is a ___
dopamine receptor gene
74
what is the most commonly studied varients of DRD4 ? what are the most frequent alleles?
VNTR in exon 3
| 7-repeats or 4-repeats
75
DRD4 has been show to affect __ and is predominantly expressed in the __
receptor function
| prefrontal cortex
76
how is DRD4-7R associated with endophenotypical expression of ADHD?
2 studies find children with 7Repeat better at sustained attention task, but another study found the opposite
77
what is the difference between children with ADHD who have 7-repeat allele of DRD4 and those who don't?
with: display extreme behaviour but no cognitive symptoms
without: at risk for poorer cognition
78
what was the neurological difference between children with ADHD who have 7-repeat allele of DRD4, and those with 4-repeat allele?
larger prefrontal grey-matter for 7R than 4R
79
2 things suggesting DRD4 is beneficial for ADHD
it protects against negative cognitive effects of ADHD
| greater prefrontal volume
80
def candidate gene
a gene with a function that suggests it is involved in the variation observed for a particular trait/phenotype
81
def homozygous
having the same alleles at a gene locus on homologous chromosomes
82
def heterzygous
having two different alleles at a particular gene locus on homologous chromosomes
83
def exon
a protein coding portion of a gene
84
def intron
a nucleotide sequence in a gene that does not code for the gene product
85
most widely used form of gene studies is __
candidate studies
86
genome wide association studies investigate __
variation in genes across the entire genome and how this influence individual differences in cognitive processes
87
why are genome-wide association studies somehwat problematic for psychological studies?
psychological/cognitive tests are not reliable enough to have low noise when testing thousands of people
88
what is the theoretical tradeoff between strength of genetic effects and allele frequency in genome wide association studies? what are the consequences of this?
common gene variants have small effects and rare variants have large effects
rare variants with small effects are hard to identify and there are few examples of common variants having large effects on common diseases
89
what did a genome wide association study reveal about candidate genes for ADHD? what new genes were revealed?
none of the candidate genes previously investigated were significant at the genome wide level
genes related to neural development FOXP2 & DUSP6
90
re: gene underpinnings of ADHD, it is likely __
polygenetic
91
def GWAS
study that surveys most of the genome for causal genetic variants
92
def genome
the entirety of an organism's hereditary information
93
what is 'genome-wide significance'?
significance threshold in GWAS is 5 x 10^-8, due to bonferroni correction for 1 million SNPs being tested
94
what are strengths of candidate gene studies? 3
can test specific hypotheses
greater power than GWAS
inexpensive
95
what are weaknesses of candidate gene studies?2
not all possible genes are investigated
| theory can miss some genetic effects
96
GWAS are hypothesis-__
free
97
strengths of GWAS 2
no prior info/theory needed
| entire genome
98
cons of GWAS
expensive
| large samples needed for effects to survive correction for multiple comparisons (1 million SNPS)
99
how can genetic influence information help? 5
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improved diagnosis
improved treatment
development of environmental interventions
understand bio- mechanisms
understand co-morbidity
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