Genetic Variation and Disease I. Whole Chromosomes to Single Bases Flashcards
Central Dogma
Flow of genetic information from DNA to protein
Genes + Enviroment –> Disease
Genetics and environment can have varying effects on predisposition of diseae
Genome and Exons
2-3% are exons
The rest of the genome is associated with regulation of genes, spaces between genes, substrate to expand genome
How do we analyse DNA
aCGH - for deletions/duplications
PCR and Sanger sequencing or Next Gen Sequencing
Mutation
A genetic variation that causes a disease
Polymorphism
A genetic variation that is prevalent in the population and not, in itself, disease causing
PCR
Can select one small piece of human genome and amplify it
Can make lots of copies
Where does a mutation act? (4)
Promoter mutation –> Reduced transcription, Reduced protein
Splice consensus altered –> Abnormal or absent protein
Base change makes new stop –> Short or absent protein
Base change alters Amino acid sequence –> Different or Non-functioning protein
What does p. and c. mean?
p. = change in peptide sequence
E.g. - c.4A>T
c. = change in mRNA
E.g. - p.Lys2Ter
Mutations and their effects
Promoter and splice site sequence changes –> Stop transcription or abnormal splicing
Base change causing amino acid change –> change protein sequence, not every base change causes disease, this may or may not reduce protein function, some mutations make protein work faster
Base change causing a premature stop codon
Insertion or deletion of bases –> In frame (shortened, functioning) & Out of Frame (reading frame disrupted)
Trinucleotide repeat expansions –> replication of trinucleotide
Variant Classification
Class 1 - Def. polymorphism
Class 2 - Prob. polymorphism
Class 3 - Unclassifiable
Class 4 - Prob. pathogenic
Class 5 - Def. pathogenic
