2 Genetic nomenclature Flashcards
What is a mutation?
○ An intrinsic change in DNA
○ Can be described at
- Chromosomal or
- DNA level
Types of mutation level?
- Genome mutaiton: whole chromosome excess or absence
- Chromosome mutation: chromosome rearrangement (i.e. translocations)
- Gene mutation: mutationi of a single gene
What type of mutation level is a translocation?
It’s a chromosome mutation
What is an allele?
Its 1 of the two copies of a locus
What type of alleles (or alternative copies of a locus can you have?
- Wild type
- The normal version, the prevailing version
- Polymorphism
- “many forms”
- More than one allele is present at a locus within a population
- May lead to disease
- Frequency of >1%
- Mutation
- It’s a permanent change in the nucleotide sequence
- Causes disease
- Rare variant - VOUS
- Allele that does not cause disease VOUS
- Frequency less than 1%
If you find a variant in the human genome, how do you call it if its >1% or <1% of frequency?
- >1% polymorphism
- <1% Rare variant
What are the types of polymorphism?
- SNP
- VNTR - variable number tandem repeats
- STR short tandem repeats
- RFLP restriction fragment length polymorphism
Difference mutation and polymorphism? Main
- Mutation = disease
- Polymorphism= benign mutation
What are “Snips” SNP’s
- Single nucleotide polymorphisms
- It’s a genetic variation among people
- It’s a single NUCLETIDE change a C for T for example
- Occur normally in normal people
- Occur once every 300 nucleotides
- There are 10 million SNPS in the human genome
- Most commonly they are located between genes
- They can act as biological markers or position hints
- If they are within a gene or closer to a gene they can have something to do about causing a disease
- Most SNPs do not cause disease
- They are useful to
- Predict responses to drugs
- Susceptibility to environmental factors
What are the 2 reasons for mutations to occur?
- Spontaneous (DNA replication errors)
- Induced
- By radiation
- Chemicals - mutagenesis
What are examples of diseases causes by advanced maternal and paternal mutations?
- Maternal - down syndrome (cytogenetic)
- Paternal - Achondroplasia (single locus)
What are the prefixes in mutations nomenclature?
- “c” for a coding DNA sequence (c.76A>T)
- “g” for genomic sequence (g.476A>T)
- “m” for a mitochondrial sequence (m.8993T>C)
- “n” for non-coding RNA reference sequence (gene producing an RNA transcript but not a protein)
- “r” for and RNA sequence (r.76a>u)
- “p” for a protein sequence (p.Lys76Asn)
c for
coding DNA sequence (c.76A>T)
“g” for…
for genomic sequence (g.476A>T)
“m” for
mitochondrial sequence (m.8993T>C)
“n” for
for non-coding RNA reference sequence (gene producing an RNA transcript but not a protein)
“r” for
RNA sequence (r.76a>u)
“p” for
a protein sequence (p.Lys76Asn)
when enumerating, which is the #1 nucleotide?
the A of the ATG (initiator)
when using gene nomenclature you have two options (C&G) what are they?
These are Reference Sequences (RS)
genomic reference sequence or coding reference sequence
- g for genome — impractical because it counts from the begining of genome so it has high numbers
- c for coding - more practical. The position 1 is the A of the ATG
There is also protein reference sequence
what are point mutations?
when there is a change in ONE SINGLE nucleotide
- the numbering always starts at the A of the ATG (methionine)
interpret this mutation
c.9A>G or p. (Lys=)
these are two forms to call a mutation
coding reference:
c.9A>G in the coding reference sequence - at the position 9 there is a substitution of A for G
protein reference:
Lys no change
It was a SILENT mutation (there was a change in thenucleotide that did not change the AA
the () means its a prediction
interpret the following mutation
c.8A>G or p.Lys3Arg
This is a missense Mutation/variant (missense - pierde sentido - there is an AA substitution
coding sequence
at position 8 A was changed to G
protein level
the 3rd AA was Lys but has changed to Arg
how do I know if this is a disease causing mutaiton /variant
check in the dbSNP for:
- allelic frequency
- has it been seen in random controls?
- seen only in patients with disease?
- is the protein functional with the change?
- is it conserved across species?
what is a :
- silent mutation
- missense mutaiotn
- non-sense mutation
- no-stop-mutation
- splicing mutation
- SILENT -change in nucleotide that does not change the AA and thus does not change the protein
- MISSENSE - change in nucleotide that changes the AA and MAY CHANGE the PROTEIN
- NON-SENSE - change in nucleotide that creates an STOP CODON
- stop codon is changed to AA and thus the reading keeps going
- splicing mutation = intron/exon splicing sites
interpret this mutation
c. 7A>T or
p. Lys3Ter or
p. Lys3*
this is a NONSENSE mutation
at position 7 there is a change in A for T
this change causes Lys to be changed to an TERMINATION codon
Which are the stop codons?
UAA, UAG, UGA
Which are the stop codons?
UAA, UAG, UGA
- UAA
- UAG
- UGA
what are NONSENSE mutations?
what do they do?
change in nucleotide that creates a TERMINATION CODON
IT creates a TRUNCATED protein (but not always
what does the NMC (nonsense mediated decay)
mecanism to clean up truncated proteins
degrades mRNA truncated
because its toxic for the cell
if you have a nonsense mutation can you write a paper on this?
no
you still need to investigate supporting info like
- allele frequency
- how frequent in the idsease
- is it only present in disease patients
conserved among species etec
interpret this mutation
c. 25T>C or
p. Ter9GlnextTer5 or
p. 9*Glnext*5
this meanes that the normal termination codon it was changed to glutamine and extended for 5 more nucleotides (because wo the stop codon the reading kept going)
Result = many AA added to protein
interpret this mutation
c.200+1G>A
this is an splicing mutation
when you see this +1 or -1 or + something or -somthing its an SPLICING mutation
- this means that at position 200+1 (at the intron) a G was mutated to A. This will likely qaffect splicing.
- this means that it may cause that an exon is skipped for example.
can silent mutation cause disease?
yes!
example PROGERIA
what is a frameshift mutation?
when the number of bases involved is not a multiple of 3
interpret the following mutation
c. 4delG or
p. Val2LeufsTer6
or
p.Val2Leufs*6
this is a frameshift mutaiton because many AAs were changed
- menas at position 4 there was a G deletion
- also at codon 2 there was supposed to be a Val that was changed for Leu and created a Ter codon in codon 6
interpret
c.16_17insAC
or
p.Leu6HisfsTer3
basically and insertion
an AC was inderte in 16&17
most common deletion?
cystic fibrosis
c.1521_1523delCTT
