1st July 2008
HGVbaseG2P Genotype and Allele representations
(where n represents the flanking sequence)
General rules for Alleles
1) Alleles are always presented in the context of 10 base upstream
and 10 bases downstream, so that the DNA strand is clear
2) Alleles MUST ALWAYS be delimited with ()
e.g., nnnnnnnnnn(T)nnnnnnnnnn for the ‘T’ allele of a SNP
3) Allele sequences can be compressed down with the appropriate
nomenclature e.g ATTTTTTAAAAAAAAA becomes (A(T)6(A)9)
4) Text-based rather than sequence-based alleles must exactly match
the representation given in dbSNP (e.g LARGEDELETION) but with the
text string additionally enclosed in Double Quotes “” and ()
eg. nnnnnnnnnn(“LARGEDELETION”)nnnnnnnnnn
General rules for Genotypes
1) Genotypes are always presented in the context of 10 base
upstream and 10 bases downstream, so that the DNA strand is clear
2) Genotypes MUST ALWAYS be delimited with []
e.g., nnnnnnnnnn[(T)]nnnnnnnnnn for a ‘T’ allele homozygote
3) For genotypes of type ‘QUALITATIVE’ (i.e., where the utilized
assay technology allows alleles to be merely seen or not seen), the
detected alleles are listed with a ‘+’ separator
e.g., nnnnnnnnnn[(G)+(T)]nnnnnnnnnn for a ‘T’ & ‘G’ allele
heterozygote
Note: virtually all genotype data today are of type ‘QUALITATIVE’
4) For genotypes of type ‘RATIO’ (i.e., where the utilized assay
technology allows alleles to be quantified with respect to each
other when more than one allele is detected), the detected alleles
are listed with a ‘+’ separator and a ratio number in front of the
opening curved bracket for each allele
e.g., nnnnnnnnnn[2(P)+1(Q)]nnnnnnnnnn for a genotype where alleles P
and Q are measured to be in the ratio of 2:1
5) For genotypes of type ‘QUANTITATIVE’ (i.e., where the utilized
assay technology allows alleles to be quantified in absolute terms
per cell), the detected alleles are listed with a ‘+’ separator and
a quantification number plus ‘x’ immediately after the opening
curved bracket for each allele
e.g., nnnnnnnnnn[(1xP)+(0.5xQ)]nnnnnnnnnn for a genotype where
alleles P is single copy per cell and allele Q is deleted from 50%
of cells
See the Nomenclature tables at the end of this document for further
examples of allele and genotype conventions
Single Nucleotide Polymorphism (SNP)
Definition: single base substitutions involving A, T, C, or G
Example allele representations:
dbSNP:
G/T
HGVbaseG2P:
nnnnnnnnnn(G)nnnnnnnnnn
nnnnnnnnnn(T)nnnnnnnnnn
Example qualitative genotype representations:
homozygote:
nnnnnnnnnn[(G)]nnnnnnnnnn
homozygote:
nnnnnnnnnn[(T)]nnnnnnnnnn
heterozygote: nnnnnnnnnn[(G)+(T)]nnnnnnnnnn
Multi-Nucleotide Polymorphism (MNP)
Definition: variations that are multi-base variations, with all
alleles being the same length
Example allele representations:
dbSNP:
ACG/TTC
HGVbaseG2P:
nnnnnnnnnn(ACG)nnnnnnnnnn
nnnnnnnnnn(TTC)nnnnnnnnnn
Example qualitative genotype representations:
homozygote:
nnnnnnnnnn[(ACG)]nnnnnnnnnn
homozygote:
nnnnnnnnnn[(TTC)]nnnnnnnnnn
heterozygote: nnnnnnnnnn[(ACG)+(TTC)]nnnnnnnnnn
No-variation (none)
Definition: Segments of sequence that are assayed and determined to
be invariant in a set of samples
dbSNP:
HGVbaseG2P:
NOVARIATION
nnnnnnnnnn(“NOVARIATION”)nnnnnnnnnn
Insertion/Deletion Polymorphism (in-del)
Definition: An insertion of one or more nucleotides in one version
of a sequence relative to another. Since the molecular event that
gave rise to this observation cannot be determined from the alleles
alone (i.e. was it an insertion or a deletion), both events are
incorporated into the name of this polymorphism type. In dbSNP, indels are designated using the full sequence of the insertion as one
allele, and a "-" character to specify the deleted allele.
Note: In HGVbaseG2P the deleted allele is specified as “_” to avoid
confusion that “-“ is interpreted as a numeric operation. Also, “_”
more appropriately reflects the alphabetical nature of the
sequences.
Example allele representations:
dbSNP:
-/T
HGVbaseG2P:
nnnnnnnnnn(_)nnnnnnnnnn
nnnnnnnnnn(T)nnnnnnnnnn
Example qualitative genotype representations:
homozygote:
nnnnnnnnnn[(_)]nnnnnnnnnn
homozygote:
nnnnnnnnnn[(T)]nnnnnnnnnn
heterozygote: nnnnnnnnnn[(_)+(T)]nnnnnnnnnn
Microsatellite or short tandem repeat (STR)
Definition: Alleles consist of a repeated sequence motif and the
number of tandem copies of this motif. Expansion of the motif into
full-length sequence will be only an approximation of the true
genomic sequence because microsatellite markers are typically not
fully sequenced and are resolved as size variants only.
Example_1 allele representations:
dbSNP:
(TAGATCATGCTGGAGCTTCTGGTGGG)28/41/49
HGVbaseG2P:
nnnnnnnnnn((TAGATCATGCTGGAGCTTCTGGTGGG)28)nnnnnnnnnn
nnnnnnnnnn((TAGATCATGCTGGAGCTTCTGGTGGG)41)nnnnnnnnnn
nnnnnnnnnn((TAGATCATGCTGGAGCTTCTGGTGGG)49)nnnnnnnnnn
...note: the () enclosing brackets around each allele
Example_2 allele representations:
dbSNP:
(A)1/10/11/T
HGVbaseG2P:
nnnnnnnnnn(A)nnnnnnnnnn
nnnnnnnnnn((A)10)nnnnnnnnnn
nnnnnnnnnn((A)11)nnnnnnnnnn
nnnnnnnnnn(T)nnnnnnnnnn
...note: the () enclosing brackets around each allele
Example_3 allele representations:
dbSNP:
(CA)11CGCACA(CG)6(CA)8/(CA)13CGCACA(CG)6(CA)8/(CA)14
CGCACA(CG)6(CA)8/(CA)14CGCACA(CG)7(CA)8/(CA)15CGCACA
(CG)6(CA)8/(CA)15CGCACA(CG)7(CA)8/(CA)17CGCA/(CA)18
CGCACA(CG)7(CA)8/(CA)20CGCACA(CG)7(CA)8/(CA)20CGCACA
(CG)7(CA)9/(CA)21CGCACA(CG)7(CA)8
HGVbaseG2P:
nnnnnnnnnn((CA)11CGCACA(CG)6(CA)8)nnnnnnnnnn
nnnnnnnnnn((CA)13CGCACA(CG)6(CA)8)nnnnnnnnnn
nnnnnnnnnn((CA)14CGCACA(CG)6(CA)8)nnnnnnnnnn
nnnnnnnnnn((CA)15CGCACA(CG)6(CA)8)nnnnnnnnnn
nnnnnnnnnn((CA)15CGCACA(CG)7(CA)8)nnnnnnnnnn
nnnnnnnnnn((CA)17CGCA)nnnnnnnnnn
nnnnnnnnnn((CA)18CGCACA(CG)7(CA)8)nnnnnnnnnn
nnnnnnnnnn((CA)20CGCACA(CG)7(CA)8)nnnnnnnnnn
nnnnnnnnnn((CA)20CGCACA(CG)7(CA)9)nnnnnnnnnn
nnnnnnnnnn((CA)21CGCACA(CG)7(CA)8)nnnnnnnnnn
...note: the () enclosing brackets around each allele
Mixed variants
Definition: Markers that are comprised of alleles of different
variation classes
Example_1 allele representations:
dbSNP:
-/A/ATTTA/T
HGVbaseG2P:
nnnnnnnnnn(_)nnnnnnnnnn
nnnnnnnnnn(A)nnnnnnnnnn
nnnnnnnnnn(ATTTA)nnnnnnnnnn
nnnnnnnnnn(T)nnnnnnnnnn
...note: the ‘-’ allele is replaced by ‘_’
Example_2 allele representations:
dbSNP:
-/G/T/TG/TTTTTTTG/TTTTTTTTTTTTTTG
HGVbaseG2P:
nnnnnnn(_)nnnnnnnnnn
nnnnnnn(G)nnnnnnnnnn
nnnnnnn(T)nnnnnnnnnn
nnnnnnn(TG)nnnnnnnnnn
nnnnnnn((T)7G))nnnnnnnnnn
nnnnnnn((T)14G))nnnnnnnnnn
...note: the ‘-’ allele is replaced by ‘_’
Named variants (Named)
Definition: insertion/deletion polymorphisms of longer sequence
features, such as retroposons (presence or absence), Alus or LINEs.
These variations frequently include a deletion "-" indicator for the
absent allele.
Example_1 allele representations:
dbSNP:
(LARGEDELETION)/-/G/T
HGVbaseG2P:
nnnnnnnnnn(“LARGEDELETION”)nnnnnnnnnn
nnnnnnnnnn(_)nnnnnnnnnn
nnnnnnnnnn(G)nnnnnnnnnn
nnnnnnnnnn(T)nnnnnnnnnn
...note: quotation marks added to text-based allele
...note: the ‘-’ allele is replaced by ‘_’
Example_1 allele representations:
dbSNP:
([CT]+[CA]+[CT]STR, LENGTH 204)/([CT]+[CA]+[CT]STR,
LENGTH194)/([CT]+[CA]+[CT]STR, LENGTHS 190-208)
HGVbaseG2P:
nnnnnnnnnn(“[CT]+[CA]+[CT]STR, LENGTH 204”)nnnnnnnnnn
nnnnnnnnnn(“[CT]+[CA]+[CT]STR,LENGTH194”)nnnnnnnnnn
nnnnnnnnnn(“[CT]+[CA]+[CT]STR,LENGTHS190-208”)nnnnnnnnnn
...note: quotation marks added to text-based alleles
HGVbaseG2P System For Genotype And Allele Nomenclature: Usage Examples
GenotypeDef (given 3 known alleles)
GENOTYPE NOMENCLATURE
P
Obs
P
Ratio
P
Count
Q
Obs
Q
Ratio
Q
Count
R
Obs
R
Ratio
GenotypeLabel
Implies that a genotyping experiment detected...
nnnnn[(P)]nnnnn
allele P only
1
0
0
nnnnn[(P)+(Q)]nnnnn
alleles P, and Q
1
1
0
nnnnn[(P)+(Q)+(R)]nnnnn
alleles P, Q, and R
1
1
1
nnnnn[(P)+(?)]nnnnn
allele P, plus an indeterminate allele
1
?
?
nnnnn[1(P)+1(Q)]nnnnn
alleles P, and Q; with signals in the ratio 1:1
1
1
0
nnnnn[2(P)+1(Q)]nnnnn
alleles P, and Q; with signals in the ratio 2:1
2
1
0
nnnnn[5(P)+4(Q)]nnnnn
alleles P, and Q; with signals in the ratio 5:4
5
4
0
nnnnn[1(P)+2(Q)+1(R)]nnnnn
alleles P, Q, and R; with signals in the ratio 1:2:1
1
2
1
1
1?
1?
R
Count
alleles P, plus an indeterminate allele; with signals in the
nnnnn[1(P)+1(?)]nnnnn
ratio 1:1
[note: only integers permitted in front of curved brackets, and all alleles must have a numeric value]
allele P only; quantified at 1 copy of P (e.g., haploid or a
nnnnn[(1xP)]nnnnn
deletion mosaic for a unique-sequence marker)
1
0
0
2
0
0
0.5
0
0
1-2
0
0
>6
0
0
1
1
0
2
1
1
1
1?
1?
allele P only; quantified at 2 copies of P (e.g., diploid for a
nnnnn[(2xP)]nnnnn
unique-sequence marker)
allele P only; quantified at 0.5 copies of P (e.g., a deletion
nnnnn[(0.5xP)]nnnnn
mosaic for a marker)
allele P only; quantified at between 1-2 copies of P (e.g., as
nnnnn[(1-2xP)]nnnnn
determined by a semi-quantitative method)
allele P only; quantified at >6 copies of P (e.g., non-unique
nnnnn[(>6xP)]nnnnn
marker at >6 copies per cell)
alleles P, and Q; quantified at 1 copy of P and 1 copy of Q
nnnnn[(1xP)+(1xQ)]nnnnn
(i.e., unique-sequence marker at 2 copies per cell)
alleles P, Q, and R; quantified at 2 copies of P, 1 copy of Q,
nnnnn[(2xP)+(1xQ)+(1xR)]nnnnn
and 1 copy of R (e.g., non-unique marker at 4 copies per cell)
allele P, plus an indeterminate allele; quantified at 1 copy of
nnnnn[(1xP)+(1x?)]nnnnn
P and 1 copy of the indeterminate allele
[note: non-integer values and range values permitted between curved brackets, and all alleles must have a numeric value]
ALLELE NOMENCLATURE
nnnnnnnnnnnnnnnnnnnnnnnnnnnnnn(T)nnnnnnnnnnnnnnnnnnnnnnnnnnnnnn
T
nnnnnnnnnnnnnnnnnnnnnnnnnnnnnn(TTT)nnnnnnnnnnnnnnnnnnnnnnnnnnnnnn
TTT
nnnnnnnnnnnnnnnnnnnnnnnnnnnnnn((T)3)nnnnnnnnnnnnnnnnnnnnnnnnnnnnnn
TTT
nnnnnnnnnnnnnnnnnnnnnnnnnnnnnn(ATTT)nnnnnnnnnnnnnnnnnnnnnnnnnnnnnn
ATTT
nnnnnnnnnnnnnnnnnnnnnnnnnnnnnn(A(T)3)nnnnnnnnnnnnnnnnnnnnnnnnnnnnnn
ATTT
nnnnnnnnnnnnnnnnnnnnnnnnnnnnnn(ATTTAA)nnnnnnnnnnnnnnnnnnnnnnnnnnnnnn
ATTTAA
nnnnnnnnnnnnnnnnnnnnnnnnnnnnnn(A(T)3(A)2)nnnnnnnnnnnnnnnnnnnnnnnnnnnnnn
ATTTAA
nnnnnnnnnnnnnnnnnnnnnnnnnnnnnn(A(T)3(A)2)nnnnnnnnnnnnnnnnnnnnnnnnnnnnnn
ATTTAA
nnnnnnnnnnnnnnnnnnnnnnnnnnnnnn(?)nnnnnnnnnnnnnnnnnnnnnnnnnnnnnn
One of the known alleles for this marker
nnnnnnnnnnnnnnnnnnnnnnnnnnnnnn(X)nnnnnnnnnnnnnnnnnnnnnnnnnnnnnn
Named allele that is an unknown allele
nnnnnnnnnnnnnnnnnnnnnnnnnnnnnn(TTTorT)nnnnnnnnnnnnnnnnnnnnnnnnnnnnnn
TTT or T
[note; permitted allele character are all IUPAC codes, plus ?, plus X]
USING COMPLEX ALLELES IN GENOTYPES
nnnnn[1(A(T)3(A)2)+1(C)]nnnnn
alleles ATTTAA, and C; with signals in the ratio 1:1
nnnnn[(1xA(T)3(A)2)+(1xC)]nnnnn
alleles ATTTAA and C; quantified at 1 copy of ATTTAA and 1 copy of C