Genetic polymorphism Flashcards
Describe the genetic variations that occur naturally in the populations
Around 1% of the human genome is different, if greater than 1% then it’s considered polymorphism. Most of variants are occur in MS regions and non coding regions.
Variants occur in Copy number variants or single nucleotide polymorphism.
Why do the genetic variations occur and are not corrected?
Because there is a tolerance, such as synonymous change, epistatic compensation or non genetically functional or genetic code redundancy
What are the causes of genetic variants?
There is synonymous change or slippage because of repeats, there is strong negative selection on the coding region but not non coding regions
What are forms of most variations? What do SNP arise from?
SNP. Synonynous, nonsense, missense can be homozygous or heterozygous
How are sequence variants in the genome assessed?
Using genome reference consortium, compare the genome to a reference
Describe the impact of variants on disease and disease management
It depends where the SNP in the genome is occuring and the type of change it arose from nonsense, missense, insertion and deletions and coding versus non coding. It may affect disease predisposition, response to treatment, disease expression
What are some examples of disease causing SNP?
NF1, loss of tumour suppressor causes tumours malignant and benign in neural crest there is a hage diversity in the expression of the disease because of the different mutations that can give rise to many different SNP.
Or FAP through APC mutation- again different expression of the disease depending on where the mutation occurs in the gene
How do they classify if a variant is pathogenic?
They use in silico modelling and associate the gene with the disease, they classify them in 5 catgories: known pathogen, unknown pathogen, variants of unknown significance, probably benign, benign
Give an example of the effects of variants in response to treatment
Thioguanine is a drug given to treat leukaemia, the TPMT catalyzes the methylation of it and reduces toxicity however patients have variants of this gene (polymorphism) causing them to either have toxicity and metabolism severe effects
How can variants be used to create personalized medicine?
They use GENOME WIDE ASSOCIATION STUDIES to see if certain alleles would be susceptible or resistant to a therapy and then strtifying them to groups based on these polymorphism
How is polymorphism related to cancer? How are they studied
There are variants of genes that can directly cause cancer or are linked to it. Through GWAS.
