突变表示方法

Nomenclature for the description of

sequence variations

J.T.

den

Dunnen,

S.E.

Antonarakis:

Hum

Genet

109(1):

121-124,

2001

Reproduced with kind permission from Prof. S. E. Antonarakis

(last modified March 7, 2001)

Questions and comments regarding nomenclature should be

directed to Professor Stylianos Antonarakis

(

rakis@

)

or

Dr.

Johan

T.

den Dunnen (

ddunnen@

). This page can also be found

at the

HGVS

site.

Contents

?

?

Introduction

Recommendations

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o

o

o

o

?

General

DNA- level

RNA-level

protein-level

Codons and encoded amino acids

o

o

genetic code

amino

acid

descriptions

(one

/

three

letter

code)

Introduction

Recently, a nomenclature system has been suggested for the

description

of

changes

(mutations

and

polymorphisms)

in

DNA

and

protein sequences [

Antonarakis, S.E. and the Nomenclature

Working Group

(1998)

Recommendations for a nomenclature

system for human gene mutations

.

. 11: 1-3]. These

nomenclature recommendations have now been largely accepted

and stimulated the uniform and unequivocal description of

sequence changes. However, current rules do not yet cover all

types of mutations, nor do they cover more complex mutations.

This document lists the existing recommendations and

summarizes

suggestions

for

the

description

of

additional,

more

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complex changes, (

shown in italics

) based on a manuscript

published in Human Mutation [

den Dunnen, JT and Antonarakis,

SE

(2000).

Mutation nomenclature extensions and suggestions

to describe complex mutations: a discussion.

. 15:

7-12] (copy in PDF format).

Discussions

regarding

the advantages

and disadvantages

of

the

suggestions

are

necessary

in

order

to

continuously

improve

the

designation of sequence changes. The consensus of the

discussions

will

be

posted

here

and

we

invite

investigators

to

communicate

with

us

regarding

these

suggestions.

Furthermore,

we invite investigators to send us complicated cases not

covered yet, with a suggestion of how to describe these (mail

to

ddunnen@ and

rakis@).

We

hope

these

pages

will be used as a guide to describe any sequence change,

ultimately evolving into a uniformly accepted reference for

mutation nomenclature description.

General recommendations

(suggestions extending the current recommendations are in

italtics)

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The term

is used to prevent confusion

with the terms

and

, mutation

meaning

change

disease-causing change

or higher in the population

The basic recommendation is to use

systematic names

to

describe each sequence variation. For this, variations are

described at the most basic level, i.e. the DNA level, using

either a genomic or a cDNA reference sequence. A genomic

reference

sequence

is

preferred

because

it

overcomes

difficult

cases, including multiple transcription initiation sites

(promoters),

alternative

splicing,

the

use

of

different

poly-A

addition signals, multiple translation initiation sites

(ATG-codons)

and

the

occurence

of

length

variations.

When,

like

in

most

cases,

the

entire

genomic

sequence

is

not

known,

a

cDNA

reference sequence should be used instead.

?

sequence variations are described in relation to a

reference sequence for which the accession number from a

primary sequence database (Genbank, EMBL, DDJB,

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SWISS-PROT) should be mentioned in the

publication/database submission (e.g. M18533)

?

tabular listings of the sequence variations described

should contain columns for DNA, RNA and protein and

clearly indicate whether the changes were

experimentally

determined

or only theoretically deduced

?

to

avoid

confusion

in

the

description

of

a

sequence

change,

preceed

the

description

with

a

letter

indicating

the

type

of reference sequence used;

o

o

o

genomic

sequence (e.g. g.76A>T)

cDNA

sequence (e.g. c.76A>T)

mitochondrial

sequence (e.g.

m.76A>T)

(from David

Fung,

Camperdown,

Australia)

o

o

?

RNA

sequence (e.g. r.76a>u)

protein

sequence (e.g. p.K76A)

to discrimintate between the different levels (DNA, RNA

or protein), descriptions are unique;

o

at DNA-level, in capitals, starting with a number

refering to the first nucleotide affected (e.g.

c.76A>T)

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o

at

RNA-level,

in

lower-case,

starting

with

a

number

refering to the first nucleotide affected (e.g.

r.76a>u)

o

at

protein

level,

in

capitals,

starting

with

a

letter

referring

to

first

the

amino

acid

(one-letter

code)

affected (e.g. p.T26P)

?

a range of affected residues is indicated by a

(underscore)

separating

the

first

and

last

residue affected (e.g. 76_78delACT)

NOTE:

current recommendations use the

(i.e. 76-78delACT)

?

for

deletions,

duplications

or

insertions

in

short

tandem

repeats, the most 3' nucleotide is arbitrarily assigned

as the nucleotide changed

?

two sequence variations in one allele are listed between

brackets,

separated by a

(e.g. [76A>C +

83G>C])

NOTE:

current recommendations use the

a separator (i.e. [76A>C; 83G>C])

?

sequence

changes

in

different

alleles

(e.g.

for

recessive

diseases) are listed between brackets, separated by a

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NOTE:

the current recommendation is [76A>C + 87delG]

?

a unique identifier should be assigned to each mutation.

The unique OMIM-identifier can be used, otherwise

database curators should assign unique identifiers

DNA level

?

nucleotides are designated by the bases (in upper case);

A (adenine), C (cytosine), G (guanine) and T (thymidine)

?

nucleotide numbering;

o

nucleotide +1 is the A of the ATG- translation

initiation

codon,

the

nucleotide

5'

to

+1

is

numbered

-1; there is no base 0

o

non-coding regions;

?

the nucleotide 5' of the ATG- translation

initiation codon is -1

?

the nucleotide 3' of the translation

termination codon is *1

o

intronic nucleotides;

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?

beginning of the intron:

the number of the

last

nucleotide

of

the

preceeding

exon,

a

plus

sign

and

the

position

in

the

intron,

e.g.

77+1G,

77+2T (when the exon number is known, the

notation can also be described as IVS1+1G,

IVS1+2T)

?

end of the intron:

the number of the first

nucleotide

of

the

following

exon,

a

minus

sign

and the position upstream in the intron, e.g.

78-2A, 78-1G (when the exon number is known,

the

notation

can

also

be

described

as

IVS1-2A,

IVS1-2G)

o

for

deletions,

duplications

or

insertions

in

single

nucleotide (or amino acid) stretches or tandem

repeats,

the

most

3'

copy

is

arbitrarily

assigned

to

have been changed (e.g. ACTTTG

TG

CC to ACTTTGCC is

described as 7_8delTG)

Description of nucleotide changes

?

substitutions

are designated by a “>”

-character

o

76A>C denotes that at nucleotide 76 a A is changed

to a C

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o

88+1G>T (alternatively IVS2+1G>T) denotes the G to

T

substitution

at

nucleotide

+1of

intron

2,

relative

to

the

cDNA

positioned

between

nucleotides

88

and

89

o

89-2A>C

(alternativelyIVS2-2A>C)

denotes

the

A

to

C

substitution

at

nucleotide

-2

of

intron

2,

relative

to

the

cDNA

positioned

between

nucleotides

88

and

89

NOTE:

polymorphic variants

are sometimes

described

as

76A/G, but this is not recommened !

?

deletions

are

designated

by

after

the

nucleotide(s)

flanking the deletion site

o

76_78del (alternatively 76_78delACT) denotes a ACT

deletion from nucleotides 76 to 78

o

82_83del (alternatively 82_83delTG) denotes a TG

deletion

in

the

sequence

ACTTTG

TG

CC

(A

is

nucleotide

76) to ACTTTGCC

o

IVS2_IVS5del (alternatives 88+?_923+? or EX3_5del)

denotes an exonic deletion starting at an unknown

position

in

intron

2

(after

nucleotide

88)

and

ending

at

an

unknown

position

in

intron

5

(after

nucleotide

923)

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