Definitions

• Mutation: any heritable change in the human genome which causes a genetic disorder
• Polymorphisms: any variation in human genome which has a population frequency >1%
  • Does not cause disease in its own right, but may predispose to common disease
• Penetrance: the likelihood of having a disease if you have a gene mutation
• Classical genetic disease (Mendelian disorders): one mutation sufficient to cause disease
  • High penetrance, small environmental contribution
• Multifactorial disease: multiple polymorphisms cause a risk of disease
  • Penetrance for any one mutation is low

Gene analysis

aCGH

• 1st line chromosome test
• Large scale - 3 million BPs
• Detects missing/duplicated pieces of chromosome
• Find polymorphisms
• Does not detect balanced rearrangements

FISH

• Uses fluorescent probes that bind only to parts of a nucleic acid sequence with a high degree of sequence complementarity
• Often used for finding specific features in DNA for use in genetic counselling

PCR

• Can select one small piece of human genome from a patient and amplify it
• Pieces can be selected to find mutations

Whole exome sequencing