Neurogenetics 2 Flashcards
What is the difference between a genotype and a phenotype?
Genotype = genetic information. Carried in the chromosome. Phenotype = how it displays (interaction of genotype with environment).
What are epigenetics?
How you can change how the DNA is expressed based on things binding to/changing how the DNA sequence is available to transcribe, or making genes more accessible, and this changes how the gene will be transcribed and used. Main methods are DNA methylation. Histone modification can mean there are large chunks of DNA that are inaccessible. Different cell type will have different epigenetic processes. These processes are important for development and activation in making sure you have the right number of chromosomes switched on or off in the female brain. Things from the environment can impact epigenetic processes. Can change how your DNA is transcribed to fundamentally change how your genes are expressed. Also changes due to aging and diet.
= plastic in both directions.
What is genomic imprinting?
Our genes are imprinted in a pattern where they’re either the genes you’ve expressed from your mother or the ones from your father that is dominant in your gene. Imprinting can happen in either sperm or egg cells, and then the chromosomes replicated from those original cells will have the same pattern of imprinting throughout the life pattern of that organism. That imprinting is set for your life time, but for children there may be a transgenerational skip (skips a generation) or may not appear at all. Some genes are methylated (switched off)
depending on whether they are inherited
maternally or paternally.
What is genomic imprinting? (continued)
One copy of gene is sufficient to cause condition (but that copy needs to be active)
Father (Michael) is carrying faulty gene in active state… 50% of his children will inherit it…
BUT gene is paternally imprinted (in sperm cells) therefore the faulty gene is there but the disease does not display.
These children will pass the faulty gene on to their offspring…
But genomic imprinting is dependent on whether the chromosaomal is maternally or parternally inherited so…
Offspring of a female carrier (Anne) have a 50% chance of carrying the faulty gene and if they do the gene will be active and the disease will display.
Offspring of the male carrier (Tom) also have a 50% chance of carrying the faulty gene, but it will be imprinted and so they will be carriers, but without displaying the disease phenotype. If then inherited maternally is “switched on” in next generation.
What is Prader-Willi syndrome?
Characterised by intellectual disability, decreased muscle tone, short stature, insatiable appetite. Rare condition. Genetic imprinting - relies on maternal deletion.
Epigenetics and the environment
What genes are switched on and off. Phenotypic differences (neuron a neuron, muscle cell a muscle cell etc). Epigenetic modifications can be stable through life course (e.g. cellular differentiation). BUT… Some affected by environment. Early developmental influence on stress resilience / depression (in later life). Maternal care (pup licking) switches on serotonin, action through 5-HT7 receptor (intracellular cascade) to activate transcription factor NGFIA, which switches on gene (Nr3C1) which expressed Glucocorticoid receptor (GR).
What is involved in human genetics?
We share over 99.9% of our DNA sequence with each other. Natural variations in our DNA are known as Single Nucleotide Polymorphisms (SNPs)
~ 3,300,000 SNPs identified through human genome project sequencing. .1% that makes us different = SNPs. In DNA sequence will have one base hair that will be different from one person to another. Throughout our genome, we have polymorphisms that change DNA between us. Use these differences to investigate. Look across the genome and look at whether SNPs are seen more commonly in people with e.g. schizophrenia – if this is the case, then can try and work out why this is causing a change in behaviour. May be that the behaviour of one SNP seen commonly in a disorder, this could be acting on the behaviour of another gene - still tells you the strip of DNA that you should be looking at. Disorders are almost always polygenetic – combination of lots of different genes make you more likely to experience a disorder.
What is involved in Alzheimer’s disease?
Will be degeneration of cells. Hallmark of disease will see amyloid plaque – cannot see this by watching someone’s behaviour, this can only be confirmed by analysis of the brain. Mutations in these genes cause Alzheimer’s Disease. Amyloid precursor protein (on Chromosome 21
– Down’s trisomy). APP gene on chromosome 21 – therefore people with down’s syndrome have 3 copies of this rather than two, making them more likely to develop Alzheimer’s.
What are genetics of schizophrenia?
Share of genetic material:
MZ twin : 100%
DZ twin or sibling: 50%
There is genetic inheritance, but cannot explain this by one gene due to polygenetic variables.
