Lecture 2- Neurogenetics Flashcards
How many pairs of chromosomes are there in humans
23
Chromosomes are present in
Every cell in the body
Natural variation in our DNA are known as
Single Nucleotide Polymorphisms
SNPs
How much of DNA is shared with others
99.9%
Mitosis produces
Somatic cells
Identical
Meiosis produces
Gametes
Half the number of chromosomes
What is homologous recombination
“Crossing over” of chromosomes
How many genes on human chromosomes
Approx 23000
Genes encode
Proteins
Genes are turned on by
Transcription factors
Transcription factors are activated during
Development or by intracellular signalling cascades from other parts of the cell
What is transcription
In the nucleus genes DNA sequence is copied into mRNA
What is translation
A ribosome attaches to the mRNA and moves along the mRNA reading each triplet codon and using tRNA to put together the amino acid chain to make a protein
What are alleles
Variants of a gene
What is Huntington’s Chorea
- Degeneration of the brain leading to progressive deterioration of movement, temperament and cognition
- Excessive repeat of CAG bases
- Dominant inheritance
What is autosomal dominant inheritance
Single copy will be dominant and lead to the disease
What is Phenylketonuria
- Mutation in the PAH gene
- Affects the enzyme that breaks down phenylalanine
- Recessive inheritance
- Can cause learning difficulties, epilepsy
What is monosomy
Single copy of a chromosome, embryonic lethal
What is trisomy
Three copies of a chromosome, very high rate of embryonic lethality
What causes Down’s syndrome
Trisomy in chromosome 21
What are the symptoms of Downs syndrome
- Smaller brain size frontal lobes and cerebellum
- Mild to moderate intellectual ability
- High risk of early onset Alzheimer’s Disease
Characteristics of Y Chromosomes
- Very few genes (smaller)
- Mostly governing make sexual function
X inactivation ensures
That the dosage of active genes is maintained in all individuals
Mutation in the gene MeCP2 turns off
The expression of unwanted genes during synapse formation
Rett Syndrome is
- X linked
- Affects exclusively females
- Mutation in the gene MeCP2
The FMR1 gene encodes the FMR protein which is thought to
Shuttle select mRNAs between the cytosol and nucleus
Fragile X is
- Most common inherited form of learning disability
- Milder penetrance to females as mosaic pattern of genes
Epigenetics
- Inherited change in phenotype
- Not due to changes in genotype
- Not a mutation in the gene but in how the gene is read
What happens without GR loss of feedback inHPA axis
Increased stress hormones, increased anxiety/ depression
Disrupted histones in sperm cells showed
Altered RNA profile in offspring
Causative genes for Alzheimer’s Disease
- APP
- PSEN1
- PSEN1
One SNP difference between APOE3 and APOE4 which
Changes an amino acid in the protein
What is concordance
The degree to which a trait is seen in 2 individuals
What genes are associated with schizophrenia
- Synaptic transmission
- Glutamate
- Dopamine
What are the difficulties in studying genes affecting behaviour
- Defining genetic and non-genetic factors
- Understanding interactions among factors
- Following steps of gene expression to behaviour
- Allowing for individual differences
Pros of animal models
- Similarity of genes
- Can breed genetically identical strains
- Control environmental conditions
- Manipulate genes by removal or mutate
Why are mice used
- 99% same genes
- Similarly organised brains
- Lots of background info on biological processes
- Targeted mutagenesis
- Short life cycle
Inbred strains allow
Comparison of these strains can tell us about how genetics influence behaviour
What is transgenic mice
- Reporter constructs to tag cells
- Constructs to target cell specific or time specific gene manipulations
What are knock-in mice
- Introduce a specific mutation
- Humanised mice
What are knockout mice
-Absence of specific gene
