how to find a novel diseased gene

Question 1

Parkinson’s disease

Answer 1

is a progressive neurodegenerative disorder with progressive death of dopaminergic neurons in the substantia nigra, and lewy bodies

Question 2

what strategy do we use to study PD

Answer 2

the index case proband only because genetic heterogeneity is expected, its difficult to have multiple gen of an adult onset disease, consanguinity and inherited mutations are expected

Question 3

what are the 2 levels of evidence when you think you have found a new gene

Answer 3

• gene level

- variant level

Question 4

what are 3 complementary strategies to collect evidence of pathogenicity

Answer 4

• genetic support
• in silico analyses
• functional studies

Question 5

variant level evidence

Answer 5

• genetic support: oo segregation
• in silico analyses: evolutionary conservation
• functional studies: cell body from patient

Question 6

gene level evidence

Answer 6

• replicative: same gene found mutated in other individuals with the same phenotype
• expression in disease relevant tissues
• guilt by association: protein encoded by candidate gene co-localizes with products of genes already implicated in the same disease
• model systems: similar phenotype in all mutant models
• gentic disruption in patients