2 Genetic nomenclature

Question 1

What is a mutation?

Answer 1

○ An intrinsic change in DNA

○ Can be described at

• Chromosomal or
• DNA level

Question 2

Types of mutation level?

Answer 2

• Genome mutaiton: whole chromosome excess or absence
• Chromosome mutation: chromosome rearrangement (i.e. translocations)
• Gene mutation: mutationi of a single gene

Question 3

What type of mutation level is a translocation?

Answer 3

It’s a chromosome mutation

Question 4

What is an allele?

Answer 4

Its 1 of the two copies of a locus

Question 5

What type of alleles (or alternative copies of a locus can you have?

Answer 5

• 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%

Question 6

If you find a variant in the human genome, how do you call it if its >1% or <1% of frequency?

Answer 6

• >1% polymorphism
• <1% Rare variant

Question 7

What are the types of polymorphism?

Answer 7

• SNP
• VNTR - variable number tandem repeats
• STR short tandem repeats
• RFLP restriction fragment length polymorphism

Question 8

Difference mutation and polymorphism? Main

Answer 8

• Mutation = disease
• Polymorphism= benign mutation

Question 9

What are “Snips” SNP’s

Answer 9

• 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

Question 10

What are the 2 reasons for mutations to occur?

Answer 10

• Spontaneous (DNA replication errors)
• Induced
  
  • By radiation
  • Chemicals - mutagenesis

Question 11

What are examples of diseases causes by advanced maternal and paternal mutations?

Answer 11

• Maternal - down syndrome (cytogenetic)
• Paternal - Achondroplasia (single locus)

Question 12

What are the prefixes in mutations nomenclature?

Answer 12

• “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)

Question 13

c for

Answer 13

coding DNA sequence (c.76A>T)

Question 14

“g” for…

Answer 14

for genomic sequence (g.476A>T)

Question 15

“m” for

Answer 15

mitochondrial sequence (m.8993T>C)

Question 17

“n” for

Question 18

for non-coding RNA reference sequence (gene producing an RNA transcript but not a protein)

Question 19

“r” for

Answer 19

RNA sequence (r.76a>u)

Question 20

“p” for

Answer 20

a protein sequence (p.Lys76Asn)

Question 21

when enumerating, which is the #1 nucleotide?

Answer 21

the A of the ATG (initiator)

Question 22

when using gene nomenclature you have two options (C&G) what are they?

Answer 22

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

Question 24

what are point mutations?

Answer 24

when there is a change in ONE SINGLE nucleotide

• the numbering always starts at the A of the ATG (methionine)

Question 25

interpret this mutation c.9A\>G or p. (Lys=)

Answer 25

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

Question 26

interpret the following mutation c.8A\>G or p.Lys3Arg

Answer 26

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

Question 27

how do I know if this is a disease causing mutaiton /variant

Answer 27

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?

Question 28

what is a : 1. silent mutation 2. missense mutaiotn 3. non-sense mutation 4. no-stop-mutation 5. splicing mutation

Answer 28

1. SILENT -change in nucleotide that does not change the AA and thus does not change the protein 2. MISSENSE - change in nucleotide that changes the AA and MAY CHANGE the PROTEIN 3. NON-SENSE - change in nucleotide that creates an STOP CODON 4. stop codon is changed to AA and thus the reading keeps going 5. splicing mutation = intron/exon splicing sites

Question 29

interpret this mutation c. 7A\>T or p. Lys3Ter or p. Lys3\*

Answer 29

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

Question 30

Which are the stop codons?

Answer 30

UAA, UAG, UGA * UAA * UAG * UGA

Question 31

what are NONSENSE mutations? what do they do?

Answer 31

change in nucleotide that creates a TERMINATION CODON IT creates a TRUNCATED protein (but not always

Question 32

what does the NMC (nonsense mediated decay)

Answer 32

mecanism to clean up truncated proteins degrades mRNA truncated because its toxic for the cell

Question 33

if you have a nonsense mutation can you write a paper on this?

Answer 33

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

Question 34

interpret this mutation c. 25T\>C or p. Ter9GlnextTer5 or p. 9\*Glnext\*5

Answer 34

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

Question 36

interpret this mutation c.200+1G\>A

Answer 36

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.

Question 37

can silent mutation cause disease?

Answer 37

yes! example PROGERIA

Question 38

what is a frameshift mutation?

Answer 38

when the number of bases involved is not a multiple of 3

Question 39

interpret the following mutation c. 4delG or p. Val2LeufsTer6 or p.Val2Leufs\*6

Answer 39

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

Question 40

interpret c.16\_17insAC or p.Leu6HisfsTer3

Answer 40

basically and insertion an AC was inderte in 16&17

Question 41

most common deletion?

Answer 41

cystic fibrosis c.1521\_1523delCTT