Behavioural Genetics

Selective breeding of animals
Twin studies in humans
Candidate gene association studies
Genome-wide association studies (GWAS)
Genome-wide complex trait analysis (GCTA)

DeFries 1978
Field mice
More anxious = less running, more defacation
Don't like bright daylight in open areas
Selected for high activity (bred high activity mice) = less defacation
Selected for low activity = high defacation

Can be beneficial to be a carrier
Unaffected but still have some benefits
Eg. sickle cell anaemia
Heterozygous = not anaemic but protected from malaria

- Tells us about variance, not proportion of a characteristic being due to genes
- Only tells us about a specific population at a given time
- Doesn't tell us about the resemblance of offspring and parents (correlation does not equal heritability)

Knopik 2017, Flint 2020
Average across a number of studies:
MZ = 0.86
DZ = 0.60
Suggests heritability ~0.50

Adenine
Thymine
Cytosine
Guanine

Proteins or STOP/termination codons

DNA helicase
H bonds broken between bases and the 2 strands separate
Free DNA nucleotides form H bonds with complementary bases (A to T and C to G) on both template strands
DNA polymerase forms phosphodiester bonds
Result is 2 daughter molecules, each an exact replica of parent DNA

Non coding section with gene

Coding section within gene

Variable Number Tandem Repeat

It's a recorded variation in the gene
194th aa
Glycine replaces valine (most common aa in population goes first)
581st nucleotide from the beginning of the gene can be T or G
Single nucleotide altered = SNP

Single nucleotide polymorphism

The gene that encodes the D4 receptor for dopamine

G-protein coupled receptor
Polymorphic: 1-7 fold repeats of a 48 base pair sequence in the 3rd cytoplasmic domain (VNTR)
Number of repeats in the VNTR affects the sodium dependent affinity for clozapine
Similar to D2 but has an affinity for clozapine (used to treat SCZ)

No. of repeats affects sodium dependent affinity for clozapine
DRD4.4 = lower dissociation constants for clozapine in absence of sodium chloride
DRD4.7 = no salt dependence
When 50% receptors are occupied: low dissociation constant means that the drug has high affinity for the receptor and fewer molecules of the drug are required to occupy 50% of the receptors.

DNA strands separated by DNA helicase
Complementary RNA bases form complementary base pairs, forming H bonds
RNA polymerase forms phosphodiester bonds
Exons and introns transcribed to produce premRNA
Introns removed
Exons spliced back together forming mRNA
Leaves nucleus and binds to ribosome
Ribosome translates mRNA, one triplet at a time
Builds chain of aa, forming protein
Peptide bonds form between aa

Exons from the same gene are joined in different combinations, leading to different, but related, mRNA transcripts
These mRNAs can be translated to produce different proteins with distinct structures and functions — all from a single gene

General transcription factors - bind to core promoter regions
Sequence-specific transcription factors - can activate / repress transcription of specific genes

FOXP2 (mutation = intellectual disability + autism)

Chromatin

Enzyme
Splits DNA wherever it can access it
Reveals sites where transcription factors can act (called DNase I hypersensitive sites)
Specific to particular cell types

SLC6A4

In the promoter region (not the gene itself)

44bp deletion = lower transcription, less serotonin transporter protein, more serotonin available
Associated with susceptibility to stress

DRD4 - gene for D4 receptor for dopamine
COMT - gene for an enzyme that metabolises dopamine and other catecholamines (eg. epinephrine, noredrenaline)
SLC6A4 - gene for serotonin transporter
OXTR - gene for oxytocin receptor

Garcia et al 2010
No. of repeats in dopamine D4 receptor gene associated with infidelity and sexual promiscuity
7+ repeats compared to 7- = more likely to be exploratory / risk taking, more likely to have one night stands, more likely to be unfaithful

Johnson 2017
25 historically most popular candidate genes associated with SCZ no more strongly associated with SCZ than non-candidate set of genes

No hypothesis created
Look for association between genes and behaviours/psych conditions

DNA obtained from >1000 pps whose behaviour on some trait has been measured
Genomes probed at ~1 million SNPs

Chip consists of a small glass plate encased in plastic
On the surface, each chip contains thousands of short, synthetic, single-stranded DNA sequences, which together add up to the normal gene in question, and to variants (mutations) of that gene that have been found in the human population

Many short probe pieces of DNA on BeadChip
Each piece of DNA specific to sequence immediately adjacent to polymorphic site
Single-stranded, complementary DNA from pp will bind to probe
Differently labelled nucleotides are added and the probe sequence will extend itself according to complementary nucleotide in pp's sequence
Stops one nucleotide before a SNP
Laser scanning system records proportions of alternative labelled nucleotides at each probed locus
Presented as a Manhattan plot

+ Savage 2018 - 270,000 pps, 205 genomic loci have tiny but significant associations with intelligence
- No single gene accounts for even 0.25% of variance in intelligence/personality
- No common allele that is present in most SCZ/autism although a few significant 'susceptible loci' have been identified

Make a direct estimate of heritability of a trait
Uses data from GWAS
Calculate how much variance in phenotype is accounted for by all the SNPs tested in GWAS

Calculate genetic similarity between each possible pair of pps
Pairs of pps rank ordered in terms of genetic similarity
Look at correlation between the rank order of genetic similarity with the rank order of phenotypic similarity

+ Davies 2011, estimate of heritability is 40% for variation in crystallized intelligence and 51% for variation in fluid intelligence
+ Most studies suggest SNP based heritability of intelligence is >0.25, similar to twin studies
- SNPs account for <10% variance in neuroticism and extraversion, different to twin studies, variation not due to SNPs, could be due to polymorphisms in the number of copies of a given gene

Down syndrome
William's syndrome
Balanced translocation

1/1000 births
Most common form of intellectual disability - avergae IQ = 55
Anatomical features (eg. protuding tongue)
Due to presence of extra copy of chromosome 21 (trisomy 21)

Aortic stenosis (narrowing of aortic valve in heart)
Wide mouth
Severely impaired visuo-spatial processing
Often verbally skilled and particularly friendly
Due to deletion of 1.5 to 2.5Mb (Megabases - equal to 1mill bases) at 7q11.23

Part of 1 chomosome exchanged with another (usually between non-homologous chromosomes, not during meiosis like crossing over)
Example:
Family carrying the translocation disproportionately likely to exhibit a major psychiatric illness
Breakpoint at 1q42.2 disrupts D1SC1 gene (disordered in SCZ 1)
BUT we now know alterations in D1SC1 are not a cause of SCZ in wider population

Carries a disproportionate number of genes that have a role in the eye / brain
Some conditions are sex linked (only occur/more servere in males), inherited from mother
Example:
Fragile X syndrome, colour blindness

Each female has 2 X chromosomes
Only one is expressed in any cell in the body
Most genes on the other chromosome are inactivated
Inactivation occurs early within the emryo
Initial inactivation is random

Dosage compensation - if both X expressed in women, but only one on men, adjustments would be needed
Mollen suggests - advantage in segregating different versions of protein in different cells, eg. trichromatic colour vision

Phenotype resulting from additive alleles depends on the number of alleles that are present
Regulates intensity of phenotype
eg more more alleles for melanin = darker skin
Not dominant vs recessive

Genes in which there is no summation of the effects of the genes
Not all members of the gene pair will be expressed - dominant vs recessive

Non additive genetic variance
Random X chromosome inactivation in female twins
Assortative mating
Differences in similairty of environments

Non-additivity of alleles for the same locus:
Heterozygosity can be advantageous or a disadvantage at a particular locus
MZ twins always share same alleles at a given locus but DZ don't always


Non-additivity of alleles at different loci:
Effect of allele at one locus may depend on allele present at different locus (epistasis) - again it will always be the same for MZ twins, unlike DZ


Assume that genes are independent and additive in their effects
This assumption of simple additivity underestimates differences between MZ and DZ in their genetic similarity (so MZ and DZ twins are more genetically different than was assumed)

MZ = identical genomes, different epxression
Many instances where one MZ twin has an X-linked condition, but not the other

Assumes ppl mate randomly
If parents choose each other for similarity/dissimilarity then DZ twins will share > or < 50% genes

Assumes environment is shared to same degree in MZ and DZ
Identical twins have special bond and more likely to develop their attitudes to the world together

- Larger the GWAS study, the poorer the phenotypic data is likely to be
- Rarely report test-retest reliability
- If a measure has low reliability, it can't be expected to correlate with the genome and show high heritability