L24 - Gene Discovery Flashcards
(9 cards)
Duchenne Muscular Dystrophy is a disease that took a lot time and a lot of work to identify the gene. What do we now have access to that would have accelerated this process?
Positional cloning. It involves the isolation of partially overlapping DNA segments that progress along the chromosome toward a candidate gene.
What can complicate the identification of the right gene from candidate genes?
Seemingly unrelated processes can be involved (protein folding, transport, gene regulation, etc.)
How are Mucolipidosis and Huntington disease examples of two of these complications?
Mucolipidosis II – Shows deficiencies of multiple lysosomal enzymes which is actually caused by a defect in another enzyme leading to a missing signal causing a lack of a whole series of lysosomal enzymes
Huntington – affects limited regions of the brain
How was the protein Factor VIII used to identify the gene that is defective in haemophilia A?
Made DNA oligo of each different codon permutations of the AA sequence
What does the identification of a human disease gene allow you to do next? (what are the next steps that this information leads to?)
A test for concerned individuals with affected family members
A test that prospective parents can test their children or select unaffected embryos from IVF for implantation
A new direction for research into potential therapies
A drug target for research into potential therapies
What is a complex or multifactorial disorder? What is a susceptibility factor?
Caused by differences in our genes (Heart disease, type 2 diabetes, asthma, etc)
Susceptibility factor – inheritance, environment
What is a GWAS, and (generally) how can it be used to identify susceptibility factors?
Genome wide association study compares genomes of non-affected vs. affected and looks for association between a SNP and a disease by identifying SNPs each person has. It is considered associated with the disease if there is a variant found frequently in people with disease. NOT necessarily causative but marks a region of genome with a causative variant.
What is personalised medicine and pharmacogenetics/genomics?
Uses genetics to predict disease development, to influence decisions about lifestyle choices or to tailor treatment to an individual.
Pharmocogenetics – how do genetic differences alter a person’s response to medicines
Clinical validity and clinical utility
Validity (how often does a positive result actually mean getting the disease)
Utility (Will the patient’s care change from knowing)
