NeuroGenetics Flashcards
The building blocks of the genetic code are called what?
Nucleotides or bases
What are the 4 different bases?
Adenine, cytosine, guanine, thymine
What are the building blocks of proteins?
Amino Acids
A specific sequence of 3 bases constitutes the genetic code for a particular what?
Amino Acid
There are 3 billion bases in the whole what?
Human Genome
How many genes code for proteins?
20-25 thousand
How do bases always pair together?
Adenine with thymine and cytosine with guanine
The DNA helix is what stranded?
Double
How is DNA bundled?
In Chromosomes
The human karyotype consists of how many chromosomes?
46
What are the 46 chromosomes made up of?
22 pairs of autosomal chromosomes and 2 sex chromosomes (XX or XY)
The function of a protein is determined by its what?
Strucutre
Structure is determined by what?
Sequence of amino acids
How are amino acids represented?
sequence of 3 bases, called a codon
Can a change to a single base change an amino acid?
Yes
Can changing the amino acid change the structure and function of the protein?
Yes
What is an SNP?
a single nucleotide polymorphism, which is a position on the genome at which the base (nucleotide) differs between individuals)
What is an allele?
A copy of a possible form of a gene
What is a phenotype?
presence of absence of a trait of interest
What is an insertion deletion variation
bases added or missing
what do you call multiple bases substituted?
Block substitution variation
Inversion variation?
Bases replaced with responding sequences from another strand
Copy number variant?
bases repeated one or more times
What qualifies as a mutation in genetic variation?
less than 1% of alleles in the population are affected
What qualifies as a polymorphism in a genetic variation?
They are common and they are greater than 1%
In females, how is excess dosage of the X chromosome managed?
one copy of the X chromosome in each cell is silenced or inactivated
What does the XIST gene do?
produces and RNA transcript that coats on chromosome and inactivates it
What does TSIX gene do?
inactivates the XIST gene
TSIX is the what partner?
Antisense
What is nature/nurture influence on phenotypes?
P = G + E Phenotype = variance from genes + influence from the environment + variance from gene environment interactions + covariance between genes and environment
What is covariance?
Some genetic variances are just more likely to exist in some environments
What is heritability?
Is the proportion of the phenotypic variance due to genetic causes
Is heritability local?
Yes, it is a local measurement, valid for a specific population at a specific time
Are disorders considered heritable?
Yes
Is ADHD, Schizophrenia and BPD considered highly heritable?
Yes
How do we study heritability in twins?
Concordance rates - if one twin has a trait or disorder, does the other one have it?
Do monozygotic twins share identical DNA material?
Yes
Do Dizygotic twins share the identical DNA material?
No, they only share about 50%
If there is a higher concordance in monozigotic twins than dizygotic twins, would this suggest there is a genetic component?
Yes!
What are monogenic disorders?
Disorders that can be identified or traced back to a single gene
Can dominant genes skip generations?
No
Autosomal disorders are equally common in both sexes, true or false?
True
What is the relationship with father and sons and X-linked disorders?
X linked disorders cannot be transferred from fathers to sons because the fathers give the sons the Y chromosome
What is the relationship between affected father and daughter of X-linked inheritance?
Daughters of affected father must be affected. They must get their fathers X chromosome
What is the relationship between fathers and daughters and recessive X linked inheritance?
fathers of affected daughters must be affected.
Square =
Male
Circle =
Female
Recessive inheritance is more common in sons. True or False?
True
What is the trait of recessive?
Both parents may not be affected by the offspring may be
What is the weird trait of recessive?
Two unaffected parents cannot have unaffected offspring
Polygenic disorders are the norm. They are?
Disorders that incorporate many genes in their cause
What is GWAS?
Genome wide association studies
What is the genome?
The complete set of chromosomes in a gamete or microorganism, or in each cell of a multicellular organism
Genome Wide Association Studies examine what?
Statistical association between phenotype and many SNP markers throughout the genome
What is linkage disequilibrium?
Chromosomes are mosaics and many variants are correlated
Quantitative traits use the what model?
Allelic dosage model. Extra doses of the minor allele have an affect on the phenotype. It is being asked if there is an association between the phenotypic measurement and the number of copies of the minor allele
Categorical and binary traits are tested using a what model?
An allelic association model. Is one of the two alternative alleles over represented in the phenotypic group?
What does a Manhattan Plot do?
Graphically summarises the results of all our individual tests of association
One point on the Manhattan plot represents what?
The outcome for a test for one SNP
Why is the p value of the Manhattan test so high?
Threshold for significance must be set high to reduce likelihood of error
Most disorders are non monogenic. True/False?
True
Smallest p equals what?
Largest difference/highest point in manhattan plot
Why do we get skyscrapers in the Manhattan plot?
multiple SNPs in linkage disequilibrium with a functional SNP OR multiple functional SNPs in the same gene
A meta analysis of bipolar found 2 genes to be associated. What is one function of these 2 genes?
Proteins from both of these genes regulate the flow of ions in and out of neurons during an action potential
What affected these genes AND also used to treat Bi-polar?
Lithium down regulated these genes
What does GWAS stand for?
Genome Wide Association Studies
Largers samples size gives more or less statistical power to discover differences
More
Schizophrenia had previously been linked to what?
Abnormal dopamine receptors
What did GWAS find in regards to schizophrenia?
A dopamine receptor gene was related to schizophrenia
GWAS can point to environmental risk factors? True/False?
True
What are endophenotypes?
- indicators of a more immediate relationship
- single quantitative traits
- Can be used on psychologically normal participants
What are examples of endophenotypes?
- Cognitive measures
- Neurophysiological measures
- Psychomotor measures
- Anomolies of basic visual perception
What does ASD and Schizophrenia have in common?
A certain disturbance in visual sensitivity
What is the pathway of link between schizophrenia and the gene PDZKI
- PDZKI interacts with NMDA receptors
- NMDA receptors play a critical role in contrast gain control in the retina
- perceptual abnormalities in schizophrenia have been suggested to arise from NMDA receptor dysfunction
Perceptual abnormalities observed in two different disorders may be linked by ____ _____ _____ that affect synaptic function
common genetic elements
Why are endophenotypes used?
They can yield larger genetic effects than diagnoses
- it avoids difficulties with diagnosing categories
- it allows testing of psycho normal patients
- biological mechanisms likely to be simpler to determine than complete psycho disorders
Is life cycle and neural complexity correlated?
Yes
What is forward genetics?
random mutations are induced
mutagenised animals are crossed with wild
animals are screened for phenotypes
animals with phenotypes are genotyped
What is reverse genetics?
TARGETED mutations are introduced and the phenotype is measured
What is the CRISPR-Cas9 system?
a natural part of a bacteriums defence against invading viruses
What can it be used for?
targeted genetic mutations in model organisms
What does RNA do in the process?
Guides the Cas9 to the targeted part of the DNA, where it cuts the DNA
What is optigenetics?
Use of microbial opsins to excite or inhibit neurons by light
How does CRISPR Cas9 manipulate genes?
Sending in correct corresponding RNA to suit the targeted DNA. Depending on what DNA we send in, we can recombine and replace the DNA strucutre
What are opsins?
groups of proteins, made light sensitive
How are opsins introduced?
Through the adeno-associated virus
Channelrhodopsin-2 responds to _____ light and ____ light allows ____ ions into the cell
Channelrhodopsin-2 pump responds to blue light and blue light allows positive ions into the cell
What does blue light process do?
Causes depolarisation which is a neural excitation
What does the yellow light process do?
Causes hyperpolarisation, which results in neural inhibition
What can stimulation of a particular rhodopsin do?
Show us what behaviours are evoked or suppressed when particular cells are excited or inhibited
What does combing the optogenic and the CRISPR-Cas9 system allow for?
- Light controlled protein editing
- Light controlled genome editing
Genetic associations with behaviour can define biological pathways involved. True/False?
False, they can only hint at the complex biological pathways involved
What can bioinformatics do?
Translate a human genetic mutation to target a homogolous gene in a model organism
What do model organisms do?
Allow for more direct measurement of structure, function and behaviour
Individuals with one or two copies of the G allele showed lower trait anxiety than individuals homozygous for the c allele is a sign of what?
Connecting genes to behaviour
What is the HTR1A SNP associated with?
Serotonin binding potential
In HTR1A, what alleles were associated with the increased binding potential?
The G allele
What is unusual about the Serotonin 1A (5-HT1A) receptor?
It is an autoreceptor and is located on the presynaptic neuron and monitors how musch serotonin is in the synapse from the pre-synaptic neuron
Reduced capacity for regulation of 5-HT release is associated with what?
Increased amygdala reactivity
Increased amygdala reactivity is associated with increased trait what?
Anxiety
Without the rs6295 G allele 5-HT binding is low and therefore what?
Greater amydala reactivity (there is less serotonin available in the synapse)
With the rs6295 G allele, there is high 5-HT binding, therefore low amygdala reactivity therefore what behaviour trait?
Low amygdala reactivity
How could low 5-HT binding lead to high amydala reactivity?
The 5-HT1A receptor is an autoreceptor so lower receptor density reduces capacity for regulating 5-HT release
In summary, presence of the G allele means what?
Low anxiety
