BMS336 Modelling Human Disease and Dysfunction Flashcards Preview

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What are the top ten leading causes of death in the US?

1. Heart disease
2. Cancer
3. Chronic lower respiratory disease
4. Accidents
5. Stroke
6. Alzheimer’s disease
7. Diabetes
8. Influencer and pneumonia
9. Kidney disease
10. Suicide


What is diabetes mellitus?

Diabetes mellitus is a disease in which the body is no longer able to carefully control blood glucose, leading to abnormally high levels of blood glucose (hyperglycaemia). Persistently elevated blood glucose can cause damage to the body's tissues, including the nerves, blood vessels. This means that the core homeostatic blood glucose system would be imbalanced. This is required for respiration.


What is chronic lower respiratory disease?

Chronic lower respiratory disease (CLRD) is a collection of lung diseases that cause airflow blockage and breathing-related issues, including primarily chronic obstructive pulmonary disease (COPD) but also bronchitis, emphysema, and asthma. Inflammation plays a key role in CLRD


What is heart disease?

Heart disease is a term used to describe several conditions, many of which are related to plaque build-up in the walls of the arteries. As the plaque builds up, the arteries narrow, this makes it more difficult for blood to flow and creates a risk for heart attack or stroke.


What is cancer?

Cancer is a group of diseases characterized by the uncontrolled growth and spread of abnormal cells. If the spread is not controlled, it can interfere with essential life-sustaining systems and result in death


What are neurodegenerative diseases?

Neurodegenerative diseases are a group of diseases characterized by the loss of nerves. There are many different types of neurodegenerative disease, including Parkinson’s disease and motor neuron disease. As their loss increases, this results in death.


What is anxiety and depression?

Anxiety and depressive disorders are poorly-characterised disorders characterised by a range of emotional, behavioural and physical symptoms


What are cerebrovascular diseases?

Cerebrovascular diseases are conditions that develop because of problems with the blood vessels that supply the brain. Four of the most common types of cerebrovascular disease are:
- Stroke
- Transient ischemic attack (TIA)
- Subarachnoid hemorrhage
- Vascular dementia


What is dementia?

Dementia is an overall term for diseases and conditions characterized by a decline in cognitive function that affects a person's ability to perform everyday activities. Dementia is caused by damage to nerve cells in the brain. Because of the damage, neurons can no longer function normally and may die. The damage eventually impairs ability to carry out core body function.
Dementia can probably arise due to loss of vascularization, loss of glial support cells, nerve degeneration


What is a model organism?

A model organism is a non-human species that is extensively studied to understand biological phenomena, with the expectation that discoveries made in the organism model will provide insight into the workings of other organisms


How are model organisms able to be used to study humans?

This is made possible due to the common descent of all living organisms and the conservation of developmental pathways and genetic material over the course of evolution


What do model organisms allow to study?

Using animal models enables a ‘whole organism’ or ‘systems’ analysis. An understanding of disease and deterioration requires a comprehensive understanding of the whole organism, and the interaction between its different components


Give example of model organisms

- Drosophila
- Zebrafish
- Chick
- Mice


Why do we use model organisms?

- It is ethically appropriate
- It is now very easy to generate a transgenic animal that has a specific mutation in a specific gene which can be used to model human susceptibility disease
- They can also be examined in large numbers to ensure that the outcomes are statistically significant and don’t just occur by chance


What is needed in a model organism?

- Need models where it is possible to examine an individual over the life course to look at progression, systems, systems interactions
- Need models where it is possible to examine Gene x Environment interactions.


How can genotype of an organism effect likelihood of disease?

- Genotype drives development and confers the potential for health and wellbeing across the life course and therefore the likelihood of some diseases
- E.g. BRCA1 gene increases the risk of breast cancer
- Disease/dysfunction is increasingly understood to arise due to Gene x Environment interactions


What are GWAS studies?

Genome wide association studies


How many protein coding genes are in the human genome?

The human genome consists of 3 billion DNA base pairs and carries about 20000 protein coding genes


What is the 100,000 genome project?

NHS started the 100,000 genomes project
- Thought that it would lead the way in personalised medicine
- They would sequence the genome of 100,000 genomes to allows scientists and doctors to understand more about specific conditions


What do GWAS studies identify?

GWAS studies identify variants that correlate with disease susceptibility. However, it does not tell us where or when the gene is expressed. Therefore, need model organisms.


How can we use model organisms to see where a protein is expressed?

Use immunohistochemistry to tell us where and when a gene is expressed or a protein is synthesised


How can we use model organisms to see the function of a gene?

Gain or loss of function approaches to tell us the function of the gene product. We can now do this in a conditional manner so that it is a tissue specific deletion of a gene


How do you produce a tissue specific knockout?

- Add lox sites either side of gene that wants to be knocked out This is referred to as a floxed allele as it is flanked by lox sites
- Put this gene back into the mouse so that the normal gene is replaced with the engineered construct
- Identify a promotor that governs a tissue specific gene. Whatever is downstream of this promotor will only be expressed in that tissue at that time. Engineer coding sequence for the enzyme cre recombinase downstream of this promotor and make a second transgenic animal.
- Combine the mice and the cre recombinase acts on the lox sites and causes the gene to be excised wherever cre recombinase is activated. It is only activated where the tissue specific promotor is activated meaning only knocked out in specific tissue


What are transgenic reporter lines?

Engineered a transgenic animal so that it gives a colour report when a gene is active (fluorescence). This is used as a way of identifying and following a cell, tissue or subcellular organ


What are the uses of transgenic reporter genes?

- Can then use these transgenic animals to visualise the cells and tissues in real time
- Can also be used to isolate specific tissues using FACS sorting. This machine sorts fluorescent cells from non-fluorescent cells so can have a pure sample of the tissue that is being investigated


How do you make a transgenic reporter line?

- Specific DNA sequence that governs gene expression in tissue of interest
- Take the coding sequence and engineer it so it is upstream to a fluorescent protein
- Make a transgenic mouse in which this gene is incorporated meaning that the reporter is only expressed in that particular tissue


Why would we want to study cell behaviours in vivo and in vitro?

- Development of new therapeutics
- Experiments that can’t be done in vivo – e.g. a recording, cell culture without influence of the body
- Used to grow organoids


What is diabetes?

A condition in which the body can’t regulate its blood glucose levels. This happens as a consequence of not producing insulin or by exhibiting a resistance to the effects of insulin


What is the difference between type 1 and type 2 diabetes?

- In type 1, the pancreas doesn’t have the cells required to make insulin meaning blood glucose builds up. This is a genetic condition.
- In type 2, the pancreas can make insulin which then enters the blood stream. However, the cells of the body are insulin resistant meaning blood glucose cannot be up taken into the cells and builds up in the blood vessels. Over time this results in a second event: the cells of the pancreas become so damaged that they become depleted meaning that the condition is exacerbated. This is a chronic progressive disease.
- Both types of diabetes have a depletion of beta cells


How is obesity related to type 2 diabetes?

Obesity is highly associated with type 2 diabetes
- If your waist circumference is less then 34 inches then there is a low risk
- Obesity is linked to the accumulation of excess fat in ectopic sites such as the liver and skeletal muscle, instead of its accumulation in adipocytes. This ectopic fat accumulation in the liver and skeletal muscle is associated with insulin resistance and type 2 diabetes.