Genetic Variations Affecting Brain and Behaviour

Question 1

What variations affect brain and behaviour?

Answer 1

Single gene disorders - affect the function or affect the expression
Gene variations/mutations
Chromosomal abnormalities
X linked conditions

Question 2

What is Huntingdon’s disease?

Answer 2

Degeneration of the striatum leading to progressive deterioration of movement, temperament and cognition

Question 3

What do you need to develop Huntington’s?

Answer 3

A single copy - 1 parent, dominant

if 1 parent has it, 50% of offspring will develop it

Question 4

Why is Huntington’s a single gene disorder?

Answer 4

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

Question 5

Why does the disease have different onsets?

Answer 5

44 repeats of CAG bases - onset 35-55

60+ repeats - early onset

Question 6

What is phenylketonuria hydroxlase?

Answer 6

It is an enzyme which breaks down dietary phenylalanine

Question 7

What is phenylketonuria caused by?

Answer 7

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

Question 8

Consequences of a build up of phenylalanine

Answer 8

Learning disabilities
Behavioural disabilities
Epilepsy

Question 9

What do you need to develop phenylketonuria?

Answer 9

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

Question 10

How can phenylketonuria be prevented?

Answer 10

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

Question 11

What are the two types of chromosomal abnormalities?

Answer 11

Monosomy: single copy of a chromosome - spontaneous abortion in early pregnancy

Trisomy - three copies of a chromosome - high rate of abortion

Question 12

What is Down syndrome caused by?

Answer 12

Trisomy in chromosome 21 - 3 copies of this chromosome (error in meiotic division)

Question 13

What does Down syndrome cause?

Answer 13

Small brain size
Facial features
Poor muscle tone
Heart condition
Early onset Alzheimers disease

Question 14

What chromosomes are important to have only 2 copies of?

Answer 14

Chromosome 1-22 - incorrect gene dosage is so disabling that the foetus dies

but 21 has minor effects

Question 15

Why is there major variation in gene dosage between sexes?

Answer 15

Males have XY

Females have XX

Question 16

What are the functions of the X and Y chromosomes?

Answer 16

Y - very few genes, mainly governing male sexual function

X - many genes that play a vital role in both sexes

Question 17

What is X inactivation?

Answer 17

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

Question 18

Why does X inactivation occur?

Answer 18

To ensure that the dosage of active genes is maintained in all individuals

Question 19

X-inactivation in females

Answer 19

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

Question 20

What is Rett syndrome?

Answer 20

An X linked disorder
Progressive neurodevelopment disorder almost exclusively affecting females, leading to mental impairment - reduced muscle tone and seizures

Question 21

What is Rett syndrome caused by?

Answer 21

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

Question 22

What does X inactivation mean for Rett syndrome?

Answer 22

That not all cells will express the mutated MePC2 gene - variable penetrance, sometimes milder

Question 23

What gender is Rett syndrome seen in?

Answer 23

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

Question 24

What is fragile X?

Answer 24

Inherited form of mental retardation

Relatively common

Question 25

What is fragile X caused by?

Answer 25

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

Question 26

What gender is Fragile X seen in?

Answer 26

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