Day 5, Lecture 3 (Aug 26): Identification of Disease-causing genes Flashcards
Positional cloning
- Identification of disease gene without prior knowledge of defective protein
- you know the positon of the gene and then pull it out and find it’s function
Functional Cloning
Identification of disease gene after identification of defective protein (this is the old way, such as how they found hemophilia)
How is next generation sequencing different from positional cloning
- Becuase you don’t have to know where the gene is located you just sequence the entire exome and find it
When genes are far apart on a chromosome than the chance of recombination is
about 50%. Recombinants will equal non-recombinants
Next Generation Sequencing (NGS)
How does ddNTP of Sanger sequencing work
it lacks the -OH group on the 3’ end so when it attaches to the DNA seqeunce the coding stops because more nucleotides can’t be added to it
- Genetic Heterogeneity
- Difference in clinical/phenotypic heterogeneity and locus heterogeneity
Examples of clinical/phenotypic heterogeneity
Challenges of multifactorial/complex diseases
This was the way they used to try and find the genetic component for complex/multifactorial diseases
- From Parametric and non-parementric came the idea of association studies
- They found some things just by chance so they moved it up to doing it across the genome (GWAS)
- The taller the blep the more associated that SNP is with the disease
- Even when found the odds ratio are so small that they can’t be used clinically
- also the issue is it a combination of the bleps making the disease or are we even looking in the right place
