Genetic Variation Flashcards
What techniques analyse genes and detect mutations
PCR
Sequencing - Conventional
- Next generation
What is a missense mutation
A base change causes amino acid to change
results in different and non-functioning protein
What is a nonsense mutation
Base change causes premature stop codon
Resulting in short or absent protein
What types of insertion and deletion mutations are there
In frame or out of frame
What is a splice site mutation
Affects splicing locations so some introns retained and some exons cut out (abnormal or absent protein as outcome)
what can mutations do to a gene
Activate or inactivate it
What 2 levels of describing mutations are there
peptide level (p.)
mRNA level (c.)
What is Polymerase chain reaction- PCR
amplifies a small piece of DNA to allow greater investigation of the many copies
What is multifactorial inheritance
When more than 1 factor is causing the trait/ health problem e.g. chronic illness or birth defect
What is the common disease common variant hypothesis
hypothesis states that the genetic component to most common disorders is due to a relatively large number of disease-causing alleles that occur relatively often in the population
What does the 97-98% of genome do that is not exons
- Regulated genes
-Spaces genes out
-Provides substrate to expand the genome
What DNA analysis can scan whole genome
aCGH
-checks for deletions and duplications
(Chromosome/ karyotype analysis for balanced rearrangements)
What DNA analysis analyses small segments of the genome
PCR, Sanger sequencing or next generation sequencing
What is a mutation
Genetic variation causing a disease
What is a polymorphism
Genetic variation that is prevalent in the population and not, itself causing the disease
What is a promoter mutation
Affects the promoter resulting in no or reduced transcription= no or reduced protein
what is the difference between mutation in frame or out of frame
In frame= alters only 1 whole amino acid in the sequence - still functions
Out of frame= alters all the amino acids after the mutation - distorted
What is the mutant if effect is c.6delA to ATGAAACATTAG
MetLysHisStop
c.= mRNA
6= 6th base
DelA= Deletion of A
ATGAACATTAG
p.Lys2ASNfs (Lys changed to Asn= frameshift)
what do Mutation Nomenclature common signs mean in mRNA
c.267G>A Substitution
c.267delG Deletion
c.267InsA Insertion
of an A
c.267+2T>A Substitution
in intron
what do Mutation Nomenclature common signs mean in peptide sequence
p.Ile122Ile No effect
p.Ile122Val Missense
p.Ile122Ter or p.Ile122* Premature
Stop / nonsense
p.ile122Thrfs deletion causes Ile
to Thr and Frame shift
What could any genetic change you see actually be
- Disease causing mutation
- Polymorphism
- Variant of unknown significance
How do we know if genetic variation is a polymorphism or a disease causing mutation
By filtering to find mutation that matters
1. Is it a known polymorphism
2. Does it affect gene function (keep)
3. Does it then explain phenotype
What are the 5 different classes of variants
class 1= Definitely a polymorphism
class 2= Probably a polymorphism
class 3= Unclassifiable
Class 4= Probably pathogenic
Class 5= Definitely pathogenic
What does a chromosome look like
Telomeres at both end
Short arm (p)
centromere
Long arm (q)
