Genetic Testing and Single Base Variation 🗸 Flashcards
Mutation
any heritable change in the human genome which causes a genetic disorder
polymorphism
any variation in the human genome which has a population frequency of >1%
Do polymorphisms cause disease?
no, but may predispose to common ones
Penetrance
the likelihood of having 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 of one mutation is low)
Gene analysis uses…
aCGH
FISH
PCR
Whole exome sequencing
Genetic filtering
aCGH
1st line chromosome test, large scale
detects missing/duplicated pieces of chromosome
finds polymorphisms
doesnt 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
sequences exome = all the exons
Genetic filtering
approx 3 million polymorphism are detected
remove the unlikely ones first to identify the pathogenic variant
Four types of mutation
missense
changes in amino acid sequence
insertion/deletion
promotor and splice site sequence changes
missense mutations
change in a single amino acid
usually caused by substitutions
most likely mutation to activate an oncogene (others tend just to inactivate the gene itself)
changes to amino acid sequences
mutation may change protein sequence which can alter protein function
mutation may result in premature stop codon
