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Flashcards in Genetics Deck (127):

What does DNA express itself into?



What do proteins interact with to give rise to cellular activity?

Proteins interact with cells and give rise to cellular activity


What is caused by cellular activity?

Neurons fire


Information in a gene shows the cell how to...

...make a protein


How does the gene show the cell how to make a protein?

Info in a gene shows the cell how to make a protein by telling it which amino acids to use and which order to put them in


What are the 4 levels of a protein's structure?

1. Primary
2. Secondary
3. Tertiary
4. Quarternary


What is the Primary structure of a protein?

The list of amino acids in order, connected by peptide bonds


What is the Secondary structure of a protein?

Amino acids that lie near each other are chemically attracted to each other and create small folds → this produces an alpha helix/beta strand

i.e. secondary structure = the alpha helix/beta strand


What is the Tertiary structure of a protein?

When secondary structures attach to each other and fold into large molecules (= domains)

Some amino acids are hidden in the interior and others are exposed on the outside where they can interact with other domains/molecules

This structure gives the protein a 3D shape that plays a role in its function


What is the Quarternary structure of a protein?

When the outer surface of a complete protein binds to other molecules


What can we detect using neural measures (e.g. MRI)?

If neurons fire together/close to each other, this can be detected using neural measures


When many neurons are active in the same area, what does this result in?

When many neurons are active in the same area, it can result in observable behaviour


What happens if behaviours become psychological?

If there is a sufficient amount of behavioural difficulties, the behaviour can get a diagnosis


What is 'aetiology'?

The factors/causes for the development of a disorder (e.g. internal factors, environment)


What is the genotype?

A person's genetic variation


What is a clinical phenotype?

The variation that captures the clinical diagnosis (e.g. autism)

The observable characteristics/traits on which you can classify groups of individuals


What is an endophenotype?

- a trait that is related to a psychiatric disorder

- it isn't directly associated with the clinical phenotype but can lead to a clinical phenotype outcome


What do molecular genetic studies involve?

These studies deal with readouts of DNA (the sequence of amino acids) and its products (RNA, proteins)


What do behavioural genetic studies involve?

- these studies use principles of shared genetic variation to infer genetic contribution to specific phenotypes
- measure whether a phenotype has a genetic contribution


What do population genetic studies involve?

These studies connect specific behavioural/clinical phenotypes with certain molecular genetic readouts


What is a gene?

- a sequence of nucleic acids that functions as a unit of heredity
- codes for the basic instructions for the development, reproduction and maintenance of organisms
- contributes to the phenotype


What is the genome?

- all of the genetic material in an organism’s chromosomes
- its size is generally given as the total number of base pairs


How many pairs of chromosomes do humans have?
How do these pairs differ between males and females?

Humans have 23 pairs of chromosomes

Males have 22 replica pairs, the 23rd pair is a sex chromosome (XY)
Females have 23 replica pairs, one is a sex chromosome (XX)


What is a locus?

The location in a pair of chromosomes where a certain allele is found


In a locus, can the pair of chromosomes found be identical?

The chromosome pair in a locus can't be identical - one is inherited from the father, the other is inherited from the mother


What is an allele?

- the base that a chromosome carries in a given locus
- sequences of base pairs that can stretch hundreds/thousands of base pairs in length


How many possible allele combinations are there?

- these are variants of the set of instructions that a gene carries


What is a nucleotide?

- phosphate molecule + deoxyribose sugar + nitrogenous base


How many nitrogenous bases are there?

- adenine
- thymine

- cytosine
- guanine


What is the sequence of nitrogenous bases in a gene?

The sequence is the 'code' of the DNA - this code tells the DNA how to build a protein


What are DNA strands (double-helix structure) made up of?

Nitrogenous bases


What are the two arms of a chromosome called?

Short arm = P arm
Long arm = Q arm


What is 'epigenetics'?

The study of how environmental and psychological factors regulate the activity of our genome without changing the DNA sequence


What is transcription?

The process by which DNA is made into RNA


What is translation?

The process by which RNA is made into a protein


What is expression?

The transcription and translation processes together


What does it mean if a gene is being 'expressed'?

The gene is switched on


What is the central dogma?

The process of gene expression


What are the stages of transcription?

1. Transcription factors gather around the DNA molecule
2. One of the transcription factors binds to a transcription initiation site on the DNA
3. Other transcription factors move towards the area
4. Helicase (enzyme) unwinds and unzips the double-helix DNA strand
5. RNA polymerase docks to the DNA and copies the DNA template into RNA
6. As a functioning messenger RNA (mRNA), it leaves the nucleus from a ribosome


Which base changes when DNA is transcribed into RNA?
What is the new base?

Thymine bases are changed into uracil bases


What are the stages of translation?

1. The ribosome reads the message, grabs amino acids that match the mRNA 3-letter codes (= codons) and builds a chain of amino acids
2. When complete, the chain of amino acids will be a functional protein


What is genetic variation caused by?

Differences in the alleles that people have at various locations across their chromosomes


What can alter gene expression?

If we modify the environment, it can alter gene expression
- some genetically influenced traits are more difficult to modify than others


What does 'SNP' stand for?

Single Nucleotide Polymorphism


What are SNPs?

Single base pairs that differ between individuals


Give an example of an SNP.

32% of the population may have the TATGACCAGCAATC allele
15% may have the AATGACCAGCAATG allele
6% may have the TATGACAAGCAATG allele

- these single nucleotide alleles are SNPs
- the 1st, 7th, and 14th positions are SNPs that vary between individuals

70% of the population may have a T (the major allele) and 30% may have an A (the minor allele) at the first SNP of the sequences
- due to the low likelihood of mutation at any single base pair, almost all SNPs have just two variants


If two chromosomes in the same locus show an SNP, what is it?

An allelic variant


On a gene, some SNPs are represented with a black box.
What does a black box represent on a gene?

The translated part of the gene (translates itself into a protein)


On a gene, some SNPs are represented with a white box.
What does a white box represent on a gene?

The transcribed part of the gene (part that is made into RNA, but not translated into a protein)


On a gene, some SNPs are represented with no box (just a line).
What does the absence of a box represent on a gene?

Nucleotides that are not transcribed or translated


SNPs serve as the principle substrate for the...

...heritability of traits


What does 'VNTR' stand for?

Variable Number Tandem Repeat


What is a VNTR?

Short repeating sequences, usually 10s of bases long
- there are 1000s of them in the gene


What does 'CNV' stand for?

Copy Number Variation


What is a CNV?

Repeating sequences that are more than 1000 bases long
- make up 0.12% of the genome
- often de novo


What can CNVs impact?

The organism's phenotype


Why/when do CNVs occur?

This variation in the sequence (e.g. bases deleted/repeated) often occurs when gametes fuse
- the parent cell has to divide its DNA in half and this process can go wrong
- with age, the repetition machinery gets weaker
- thousands of bases can be mistakenly repeated


What are transposons?

Elements in the genetic sequence that can move around between different chromosomes
- i.e. DNA isn’t fixed/rigid


What do we use PCR for?

Polymerase Chain Reaction

Used for measuring one variant (sequence) at a time


What do we use microarrays for?

Used for measuring millions of variants (sequences) at a time
- used in genome-wide association studies


What common animal models are used by genetic researchers?

- mice
- C. elegans (nematode worm)
- Drosophilo (fruitfly)
- zebrafish


Why are animal models preferred to human models?

- gene manipulations are easier
- they have simpler phenotypes
- their life cycle is shorter


Humans have a variety of complex phenotypes.
How can we test them?

Mostly observational/something you can record rather than something we can manipulate by knocking off or inserting a gene
- unethical to manipulate human genetics


What does genetic engineering involve?

- can cut and paste a new portion into a gene
- can remove a portion of the gene (using molecular scissors and glue) to create an animal without that gene

--> see how the animal's behaviour is affected


What is an animal who has had a gene removed called?

Genetic knockout model


What does viral transfection involve?

- take a gene with a defective allele and replace it with another gene
- use restriction enzymes/ligases to cut out the gene


We can switch off a gene using optogenetics. What does this involve?

- insert a light-sensitive switch for the gene
--> when the animal is exposed to light, the gene is switched on
--> when the light colour changes, the gene is switched off


What are mutations?

Alleles with minor allele frequencies up to 1%


What is a polymorphism?

An allele (e.g. SNP) with a minor allele frequency more than 1%


What are included in 'copying errors'?

- point mutations
- deletions
- duplications
- translocations
- inversions


When do copying errors occur?

During DNA replication


What types of mutations are central to the evolutionary process?

Mutations that occur during the replication of sperm/egg cells


Why are mutations that occur during the replication of sex cells so important for the evolutionary process?

Such mutations can be transferred to the fertilised ovum and eventually to every cell in the offspring's body, including the offspring's own germline cells and potentially any descendants of the offspring
- this is how mutations are 'introduced' into a population


In which area of the gene do new mutations usually arise?

In chromosomal locations that have no phenotypic effect (= ‘junk DNA’)


What happens to mutations that affect the phenotype of the organism?

They usually degrade its tightly coordinated performance and are kept at low but calculable frequencies by natural selection


Mutations increase the risk of...

...having adaptations that malfunction


What can mutations change about a protein?

Mutations can changes a protein's structure


Changing a letter of DNA leads to a change in an amino acid letter in the primary structure of a protein. What can this lead to?

This may change the attractions between amino acids

Changing the attractions may alter the formation of the alpha helix/beta sheet (secondary structure)

Changing the alpha helix/beta sheet disrupts the shape of domains (tertiary structure)

Changing the shape of domains changes the set of other molecules that the protein can bind to (quarternary structure)


What are the two main study designs for genes?

1. Behavioural genetics in twins
2. Genetic association studies


What can we deduce from behavioural genetics in twins?

If there is a strong genetic component in a phenotype, there will be higher concordance between MZ twins than DZ twins

If concordance between MZ and DZ twins is the same, it is less likely that there is a genetic component


What are the 3 ways we can measure genetic variation?

A: Additive (genetic) variance
C: Common (shared) environment
E: Non-shared environment


Which component (A, C, E) differs between MZ and DZ twins?

The A (additive variance) component differs between MZ and DZ twins

MZ: A = 1.0 (the same)
DZ: A = 0.5

C = 1.0 (if both MZ and DZ twins share the same environment)
E = 0


MZ twins should have exactly the same genes, but this isn't always the case.

What might explain this?

Bruder et al. (2008) - CNVs explain some MZ co-twin differences in physical conditions (e.g. Parkinson's)

Fraga et al. (2005) - epigenetic events

Segal (2000) - differences in intrauterine conditions and post-natal experiences


What are epigenetic events?

Processes that are associated with gene expression


What are the basis of genetic association studies?

We can measure parts of the genetic sequence and see whether individuals with certain types of sequences have traits related to a particular disorder


What approaches do genetic association studies combine?

They combine molecular genetic and population genetic approaches by asking whether phenotypes are more prevalent in groups of individuals with certain genetic variant/s


Which two ways can we do human genetic studies?

1. Determine the genetic component in a disorder (using behavioural genetics studies)

2. Look for whether certain variants are more associated with a given disorder or not


Whole-genome association studies have found alleles that explain significant variation for certain traits.

Which researchers have found such evidence, and for which disorders/illnesses?

Spinola et al. (2006) - lung cancer

Bierut et al. (2007) - nicotine dependence


How do we know that a disorder is genetic?

If it has high heritability


What is 'heritability'?

The proportion of variance in a phenotype that is explained by genetic effects (A) after accounting for phenotypic variance due to shared (C) and non-shared (E) environments


What are the heritability rates of ASD, SZ, major depressive disorder and bipolar disorder?

ASD = 93%
SZ = 81%
MDD = 37%
Biopolar = 1.5%


What percentage indicates a high genetic contribution?

Any heritability over 50% indicates high genetic contribution

Anything less than 50% suggests that there is a larger influence from the common (C) or non-common (E) environment


What is the general population prevalence of ASD, SZ, major depressive disorder and bipolar disorder?

ASD = 1%
SZ = 0.5-1.5%
MDD = 13%
Biopolar = 1.5%


What is the 'global lifetime prevalence' of a disorder?

The number of people that, at some point in their life, have experienced/suffered from the disorder


What is the 'point prevalence' of a disorder?

The number of people with the disorder at a certain time


Prevalence rates might provide indirect cues as to whether a disorder is restricted to...

...a certain age range, environment or part of the world.

--> if this is the case, it supports the environmental argument of disorders


Disorders may not be defined strongly but can share observable features.

What did a researcher/s find about commonalities between bipolar disorder, SZ and depression?

Bearden et al. (2004) – bipolar, SZ and depression share psychotic symptoms
- the disorders themselves aren’t natural kinds or independent units because some of their features (endophenotypes) are shared


Which might have a stronger genetic component - shared endophenotypes or non-shared endophenotypes?

Non-shared endophenotypes


Serretti et al. (2013) tested 30,000 pps, investigated shared genetic underpinnings.

What did they find?

Many people with psychiatric conditions shared underlying genetic variations → disease vulnerability


Why will people have shared genetic variation?

Because they share phenotypic variation


What is 'autism'?

A neurodevelopmental condition
- atypical social and communicative behaviour
- RRBs


When can the earliest diagnosis of autism be made? Why is this significant?

The earliest diagnosis is at 18 months
- this suggests that something happens in early development that influences the development of autism


Autism is a 'spectrum disorder'.
What does this mean?

It isn't a singular entity - people don't have it or not have it

There are a variation of individual capabilities


What are the two types of families with autism?

- simplex family
- multiplex family


What is a simplex family?

Families with only one proband with autism


What proportion of families with autism are simplex families?

Simplex families account for 1/5 of autism cases


In simplex families, what causes autism?

During the formation of the gametes, cells that produce DNA are produced by a replication process in the mother's cells
If this process goes wrong, there may be chunks of DNA that are replicated more than they should have been/deleted


What is a multiplex family?

Autism runs through the family


In multiplex families, what causes autism?

Autism is believed to be due to many small genetic variants (e.g. snips) being passed through generations
- no individual variant is strong enough to create the diagnosis on its own
- if the variant is carried through generations and added to other variants, it might create a diagnosis


In which type of family of autism do de novo CNVs often happen?

Simplex families


Genes are not in isolation.


Genes produce proteins that interact with proteins from other genes


What approaches are there to gene hunting?

- carpet bombs approach
- guided-missiles approach


What is the carpet bombs approach?

- don't take into account previous knowledge that comes from animal models/molecular studies about which molecules are involved in certain behaviours

- hypothesis-free


How do we study genetic variation using a carpet bombs approach?

- we study every genetic variation that we can using MICROARRAYS

- e.g. whichever gene is significant (different) between people with autism and healthy controls will be the gene for autism


What type of study is the carpet bombs approach an example of?



What is the guided-missiles approach?

- we have a clear idea of which gene is associated with a disorder from studies on animal models


How do we study genetic variation using a guided-missiles approach?

We study every variation within that gene using PCR


What type of study is the guided-missiles approach an example of?



What features should an animal model have?

- a homologous human phenotype
- a short reproductive cycle
- easy to manipulate their genes (knockout, viral transfection, optogenetics)


Why is it difficult to create a model of an autism-related feature in certain animals, such as fruit-flies?

It is hard to create a model of an autism-related feature in animals like fruit-flies because they don’t show much social behaviour


What animal is common used in autism genetic studies?

Mice show social behaviour (interact with others, display a preference for conspecifics compared to strangers)
- mice have a homologous human phenotype of social behaviour


Why is it important that animal models have a short reproductive cycle?

We can knockout a gene and see the impact that it has on their behaviour within 6 weeks


What is required to make an animal model for autism?

We need a good assay of social behaviour to make an animal model for autism
- we must create an assay of preference for familiar conspecifics


What is the 3-champer approach task?

A knockout mouse is put into the central chamber
There are 2 chambers either side that the mouse can go through to
One chamber contains a novel object, the other contains a novel object + a conspecific


What does the 3-champer approach task measure?

It measures the amount of time that the knockout mouse spends with the novel object alone vs. novel object + conspecific


Why is the 3-champer approach task a good method to study autism?

A key feature of autism is that they prefer to spend time alone with a non-social object
- we can use this task to measure how socially motivated the knockout mouse is
- we can look at whether a gene of interest (one that is linked to autism) impacts the behaviour of interest (i.e. social behaviour)


What factors do we take into account when evaluating psychiatric genetics research?

- decide if a disorder is genetic
- test the global lifetime prevalence of the disorder
- look at how the disorder is inherited in families
- test for genes that are associated with the disorder
- make an animal model