Behavioral genetics

Definition of variable g

the variable summarizes positive correlations among different cognitive tasks, reflecting that and individuals performance on one task is comparable to another task.

What is the heritability of g and why?

Heritability of g is around 50% and it increases as people age because people are more able to change their environments to suit their g as they age.

What are environmental influences of g? Example?

stimuli in the environment that can change gene expression like childhood adversity affecting individuals with the met allele.

Define genetic correlation?

the extent to which genetic influences on one gene also affect another gene

Overview of PKU

• Arg replaced by Trp on chromosome 12.

• Cannot eat phenylalanine and causes intellectual disability

• recessive inheritance

Overview of FXS

• autistic like behavior, anxiety, mental impairments

• excess CGG repeats cause hypermethylation of FMR1 gene

• mothers with between 54 and 200 repeats have anticipation phenomenon

• X chromosome linked

Overview of down syndrome

• 3 different types

• regular, mosaic, and translocation

• not heritable

• only translocation DS is heritable

What is genetic imprinting

epigenetic phenomenon when certain genes are expressed in a parent of origin manner

What is the significance of the UBE3A gene?

• the gene is on chromosome 15 but only expressed maternally

• has control center which codes for antisense RNA to silence gene expression

• control region is methylated on mother chromosome

AD heritability

60-80%

Early onset AD genes

• presenilins

• APP

• PS1

• PS2

Late onset AD genes

APOE-4

positive SZ symptoms

• hallucinations

• delusions

• thought disorders

negative SZ symptoms

• social withdrawal

• appearing lack of emotion

• loss of motivation

• loss of interest in daily activities

COMT SZ hypothesis

• Met/Met genotype has lower enzymatic activity and higher dopamine levels in PFC which messes up executive function

• Val/Val genotyped individuals are much more likely to have SZ if they are cannabis users

DRD4 SZ hypothesis

• DRD4 gene has a VNTR polymorphism

• more repeats gives people the long allele and the long allele has altered dopaminergic signaling making them more likely to have SZ

Glutaminergic SZ hypothesis

• bad NMDA function makes GABA cells unable to inhibit Glutamine neuronal activity

• GRIN1 mutations cause low NMDA activity

• GRIN1 plus GRIN2B mutations cause the most risk for SZ

SZ Disc 1 hypothesis

• Disc1 gene can have a chromosomal translocation which can cut off the DISC1 gene

• DISC1 is important for multiple functions in the brain

• Camp signaling, neurogenesis, Synaptic function

CNVs and epigenetics in SZ

• there are large and rare CNVs establishes in SZ

• ST6GALNAC1 is hypomethylated in affected MZ twins

• CpG site on ZNF659 is hypermethylated in SZ and hypomethylated in BD

Depression heritability

50%

SlC6A4 gene on depression

• codes for serotonin reuptake transporter

• can have long or short allele

• short allele is associated with depression

• short allele is more sensitive to environmental stresses

• on chromosome 17

Depression and ACE gene

• ACE is involved with cardiovascular disorder

• ACE SNP can cause abnormal ACE activity and HPA axis hyper activity

Bipolar disorder SNPs and significance

• ANK3 regulates the assembly of voltage gates sodium channels

• CACNA1C is a subunit of the L-type voltage gated caclium channel

BD diathesis hypothesis

• people have predisposition factors for BD which can be activated due to severe stress

Anxiety disorder heritability

30-40

ADHD GxE, GGxE

DAT + nicotine = ADHD

DRD4 + DAT+ nicotine= very very likely ADHD

Transcriptome dynamic

• The transcriptome dynamic describes how genes involved in brain development are expressed in a time-, brain region-, and sex-specific manner.

  The higher number of differentially expressed genes in males could help explain the higher occurrence of neurodevelopmental disorders in males than females (e.g. ASD, ADHD).

   

  One of the mechanisms that could drive the transcriptome dynamic is dynamic changes in DNA methylation (epigenetic mechanism). These changes, in a gene-specific manner, can help controlling the silencing or activation of gene expression throughout prenatal development.

Heritability of postnatal changes

>70%

Role of MECP2

• mutation cause severe neurological phenotypes

• expression increases with age

• common sequence variations in a region around MECP2 show associations with brain size

• important transcriptional activator and repressor

High SES is correlated with

higher left hemisphere lateralization

ASD causes

• deprivation(maternal/sensory)

• genetics

• immune dysfunction

• nutrition

• trauma

Developmental disorder definition

impairments to the growth of the brain and central nervous system

ASD concordance

• 80 percent in MZ

• 10 percent in DZ

ASD de novo mutations

• 15q11-q13 duplication

• missense mutations in NLGN-3

• frame shift mutation in NLGN-4

• NLGN associate with SHANK3 and SHANK3 mutations are common in ASD disorders

Environmental factors of ASD

• Genetics

• Teratogens

• Advanced parental age

• low birth weight

• prenatal infections