Brain and Behaviour (5): Neurogenetics

Genetics

Study of inherited variation and how traits are passed down through generations

Chromosomes

Tightly wound coils of DNA. Humans have 23 pairs.

Genes

DNA segments on chromosomes that encode proteins. They carry instructions that determine traits.

DNA

Contains the genetic information and instructions for protein synthesis. Has a double helix structure with complementary base pairing (A-T, C-G)

What are Single Nucleotide Polymorphisms (SNPs)?

Variations in DNA (0.01%) that make us genetically unique

What is the difference between mitosis and meiosis?

• Mitosis produces identical somatic cells

• Meiosis produces gametes with half the chromosomes.

What allows Genetic Diversity?

Homologous recombination (“Crossing Over” of chromatids)

Transcription

Process where RNA is synthesised from a DNA template

Translation

Process where ribosomes use mRNA, reading each triplet codon and using tRNA to put together amino acid chains to make proteins.

What are Mendel’s 3 Laws of Inheritance

• Segregation: Individuals have 2 alleles (variants) of a gene from each parent, which segregate during reproduction, giving one to each gamete (sperm/egg).

• Independent Assortment: Genes for traits are inherited independently of each other.

• Dominance: Some alleles are dominant and some are recessive.

What is the difference between genotype and phenotype?

• Genotype: Genetic information

• Phenotype: Observable traits

What disorders can mutations in genetic sequence lead to?

• Single gene disorders

• Genetic mutations:

  • Affect function (e.g. huntington’s, PKU)

  • Affect expression

• Chromosomal Abnormalities

• X-Linked Conditions

Huntington’s Chorea

(Dominant) Inherited disorder that causes neurons in the brain to break down and die → loss of controlled movement. It is caused by a gene disorder on chromosome 4.

Phenylketonuria (PKU)

(Recessive) Inherited disorder caused by a mutation in the PAH gene. If untreated it leads to phenylalanine build up → intellectual disability & health problems.

What causes Down Syndrome?

Trisomy 21 (three copies of chromosome 21)

X-Linked Conditions

Genetic disorders caused by mutations in genes located on the X chromosome. Therefore there is major variation between sexes.

X-Inactivation in females

In females, one X chromosome is randomly silenced (condensing into a “Barr Body”) in each cell to balance gene dosage, which means not every cell will express the gene.

Rett Syndrome

X-linked neurodevelopmental disorder affecting ~exclusively females → Disabilities. It is caused by mutation in the MeCP2 gene on the X chromosome.

Fragile X Syndrome

X-linked inherited learning disability caused by repeated CGG expansion in FMR1 gene. Symptoms predominantly appear in males as females have milder penetrance due to X-inactivation.

Epigenetics

Study of changes in gene expression without altering DNA sequence. Changes result from modifications to DNA that regulates if genes are turned on/off.

Animal Evidence environmental factors can affect gene expression

Heckman et al. (2010): Maternal care (licking & grooming) can affect and heighten GR (glucocorticoid receptor) gene expression → lower anxiety & stress.

DNA Methylation

Addition of methyl groups to DNA, silencing gene expression.

Transgenerational Epigenetics

Environmental effects passed to offspring through epigenetic changes.

What have Genome-Wide association studies (GWAS) shown about Alzheimer’s Disease?

Rare alleles (e.g. APOE4) can contribute to the risk of obtaining Alzheimer’s.

Concordance

The likelihood that a trait appears in both members of a twin pair.

What did Gottesman’s (1991) Twin Studies suggest about Schizophrenia?

SZ has a strong genetic component but other factors play a part (48% MZ, 17% DZ concordance)

Why are mice used in genetic research?

• Genetic similarity to humans

• Fast breeding

• Short Life Cycle

• High experimental control

What is a knockout mouse?

A mouse with a gene deliberately deactivated

What is a knock-in mouse?

A mouse with a specific mutation inserted

What is the purpose of using inbred mouse strains?

To study genetic influence on behaviour under controlled conditions.

How is Rett syndrome studied using animal models, and why is this important?

1. In mouse models, knocking out MeCP2 replicates Rett symptoms.

2. Using an inducible knock-in, researchers switched the gene back on with drug treatment - reversing symptoms → potential for therapeutic intervention in humans.