Genetic Variation and Disease #2 Flashcards
Continuous vs Dichotomous traits
Disease prevalence or trait average different between sexes, ethic groups etc.
Continuous:
- trait will be measured as a range
- Average +/- deviation in a population are a focus
Dichotomous:
- traits is measured as a yes/no for having it
- behind the scenes there is a range of phenotypes - our a certain threshold is considered having the trait/disease
Describe how the extent to which the environment and genes contribute to polygenic traits differs
Both genes and environment contribute to polygenic traits
- the contribution of each varies for each trait. eg, asthma, heart disease, autism
- purely environmental traits eg. tattoos, flamingo pigment
- purely genetic traits eg. eye colour, monogenic diseases
Describe what the majority of traits are (polygenic or monogenic)
Vase majority of traits are complex/polygenic traits (even things we may think of as simple monogenic traits are usually complex, ie. eye colour - 16 different genes contribute so its actually a complex trait)
- monogenic diseases are usually rare, affecting very few people
- polygenic diseases are very common and are the leading causes of death in the western world (eg. diabetes, hypertension, heart disease, etc.)
- people can be affected by more than one complex disease at once
What are the two key concepts of polygenic traits
- any type of protein can have a genetic variant/change in function
- protein anywhere in a pathway/process can be affected
- start: entire pathway will fail to take place (generally the worse affect)
- middle: metabolism ends in the middle of the pathway?
- end: can cause accumulation of highly toxic ‘intermediates’ because the final product is not being made so there is a buildup of the ‘intermediate’
Describe genetic studies of polygenic traits
Genetic studies of monogenic traits look for inheritance patters
However, genetic studies of polygenic traits look for correlations or associations
- cannot infer causation from these studies alone
- best at finding common variants with a ‘moderate’ to ‘weak’ effect
Pros:
- polygenic traits are usually common
- can find a lot of people with the condition you are studying
- can design studies to account for environmental factors (eg. twin studies)
Cons:
- not looking for one gene/variant (multiple ways to get the same phenotype)
- range of phenotypes possible (how you measure/define condition can change results)
Describe genome wide association studies
- they look to see if any genetic variants are associated with a phenotype of interest
- take-home here is that it is very hard to determine polygenic traits and what genes are associated with them, but we can try by taking people with those genotypes and sequencing their whole genome to look for variants.
- use many variants spread throughout the genome
- perform an association analysis for every marker
- each marker considered separately
What is cancer caused from?
Normally cells grow and divide to form new cells as the body needs them (for growth, repair and replace old cells), and when they cells grow old or damaged they die (apoptosis).
Cancer is a collection of related diseases, and it is characterised by an uncontrolled growth of cells, forming a tumour.
- cells no longer repose appropriately to signals that control cell growth and death leading to uncontrolled growth
- over time, cancer cells become increasingly resistant to growth control signals and divide even more rapidly
Describe the terminology used when talking about cancer
Genetic variant: as specific difference in DNA sequence between individuals (includes hereditary differences and de novo differences)
Mutation: the process by which new genetic variants arise (a somatic mutation is created when mutations occur within some of an individuals cells) - used to talk about cancer
Somatic: all of the different types of body cells
Germline: reproductive cells involved in passing on genetic information to the next generation
Describe cancer causing mutations
Cancer is a result of an accumulation of mutations
- somatic mutations occur all over the body all the time, but usually the body’s immune system removes these cells before they cause problems.
- mutation occurs as a result of many processes (errors in DNA replication or exposure o carcinogenic chemicals or agent)
- the risk of cancer increase with age as cells undergo more cell divisions (more changes to create and accumulate mutations)
Describe the cancer causing genes
Proto-oncogenes -> oncogenes
- called oncogenes once they are mutated
- genes encoding proteins that promote cell growth (proteins that stimulate cell division)
- mutations that increase the activity of these genes increase cancer risk (gain of function mutation = dominant allele)
- promote cell growth when it is not needed
Tumor supressor genes:
- genes encoding proteins that prevent uncontrolled cell growth (eg. proteins that inhibit cell division, or proteins that prevent other mutations [ie. DNA repair enzymes])
- mutations that decrease/remove activity of these genes increase cancer risk (loss of function mutation = recessive allele)
- promote cells growth instead of preventing it
- recessive affect so need both alleles to be mutated for it to have any effect
Describe what different mutation in these cancer risk genes does
Proto-oncogenes and tumor supressor genes work together to control normal cell growth (accelerator and break)
- A proto-onco gene mutates into an oncogene and accelerated growth. tumour supressor genes are still working to prevent uncontrolled growth, so no cancer, just increased risk
- Both versions of a tumor supressor gene mutate and no longer prevent cell growth. photo-oncogenes are still only trying to grow cells at a ‘regular’ rate, so no cancer, just increased risk
- together mutations to oncogenes and tumor supressor genes cause cancer, by causing uncontrolled cell growth, which increases mutation rate of cancer cells
Describe hereditary cancers
Inherited genetic variants can increase a persons’ changes of developing cancer
- hereditary cancers often develop at a younger age than non-hereditary cancers
- require less mutations to accumulate before cancer develops
- these do not garantee you will get cancer, just increase your risk because you already have a mutation, so need less to get the three mutations required for cancer
