Genetic Variations Affecting Brain and Behaviour Flashcards
What variations affect brain and behaviour?
Single gene disorders - affect the function or affect the expression
Gene variations/mutations
Chromosomal abnormalities
X linked conditions
What is Huntingdon’s disease?
Degeneration of the striatum leading to progressive deterioration of movement, temperament and cognition
What do you need to develop Huntington’s?
A single copy - 1 parent, dominant
if 1 parent has it, 50% of offspring will develop it
Why is Huntington’s a single gene disorder?
It is a disorder in the gene 4 - caused by excessive repeat of CAG bases
normal - 11-34 copies of this base repeat
huntingtons - over 40 copies
Why does the disease have different onsets?
44 repeats of CAG bases - onset 35-55
60+ repeats - early onset
What is phenylketonuria hydroxlase?
It is an enzyme which breaks down dietary phenylalanine
What is phenylketonuria caused by?
Mutation in the PAH gene - if you don’t break it down in neurodevelopment, get a built up of amino acid which is toxic to the developing brain
Consequences of a build up of phenylalanine
Learning disabilities
Behavioural disabilities
Epilepsy
What do you need to develop phenylketonuria?
2 bad copies of the gene
if only one gene, sufficient enough to make enough enzyme to break down PAH
if you have 2 mutations - 1/4 offspring will carry it
How can phenylketonuria be prevented?
Screening at birth in the UK, can be prevented by diet - if someone can’t break it down, give them the diet so they won’t have the break up of toxic acid
easy to deal with the mutation - environment interacting with genes
What are the two types of chromosomal abnormalities?
Monosomy: single copy of a chromosome - spontaneous abortion in early pregnancy
Trisomy - three copies of a chromosome - high rate of abortion
What is Down syndrome caused by?
Trisomy in chromosome 21 - 3 copies of this chromosome (error in meiotic division)
What does Down syndrome cause?
Small brain size Facial features Poor muscle tone Heart condition Early onset Alzheimers disease
What chromosomes are important to have only 2 copies of?
Chromosome 1-22 - incorrect gene dosage is so disabling that the foetus dies
but 21 has minor effects
Why is there major variation in gene dosage between sexes?
Males have XY
Females have XX
What are the functions of the X and Y chromosomes?
Y - very few genes, mainly governing male sexual function
X - many genes that play a vital role in both sexes
What is X inactivation?
Switches off one copy of X chromosome during embryogenesis - one of the two X chromosomes is inactivated in cells - so each female has one functional copy of the X chromosome in each cell
Why does X inactivation occur?
To ensure that the dosage of active genes is maintained in all individuals
X-inactivation in females
Female is a mosaic of clones derived from different embryonic cells - within a close, all the cells inactive the same X but between them, the choice is random - if she is a carrier of an X linked disease, has problems
What is Rett syndrome?
An X linked disorder
Progressive neurodevelopment disorder almost exclusively affecting females, leading to mental impairment - reduced muscle tone and seizures
What is Rett syndrome caused by?
A mutation in the gene MeCP2 - this turns of the expression of unwanted genes during synapse formation
gene on one copy of X chromosome - spontaneous mutation
What does X inactivation mean for Rett syndrome?
That not all cells will express the mutated MePC2 gene - variable penetrance, sometimes milder
What gender is Rett syndrome seen in?
Only females - they don’t express the mutation in every cell, some will be switched off. they could have a good copy of the MePC2 gene
not males - every copy is bad, so if they have the mutation, the embryo will die
What is fragile X?
Inherited form of mental retardation
Relatively common
What is fragile X caused by?
Mutation in one end of the FMR1 gene - amplification of a CGG repeat (200+ copies) - the FMR1 gene encodes the FMR protein which is thought to shuttle select mRNAs
What gender is Fragile X seen in?
Males - they always will inherit it as due to no inactivation, will be throughout the brain, see it more frequent
Females - milder penetrance - due to X inactivation, not always recognised
